Journal - Dolutegravir - Supplementary Appendix

Supplementary Appendix
Supplement to: Turkova A, White E, Mujuru HA, et al. Dolutegravir as first- or second-line treatment for HIV-1
infection in children. N Engl J Med 2021;385:2531-43. DOI: 10.1056/NEJMoa2108793
This appendix has been provided by the authors to give readers additional information about the work.
ODYSSEY main paper supplementary material
Table of Contents
S1 ODYSSEY Trial Team ........................................................................................................................................... 6

S2 Primary and secondary outcome measures in ODYSSEY ................................................................................... 9
Table S2.1 Primary and secondary outcome measures in ODYSSEY ......................................................................... 9
S3 Statistical methods .............................................................................................................................................. 10
S3.1 Analysis populations ....................................................................................................................................... 10
S3.2 Primary endpoint ............................................................................................................................................. 10
S3.3 FDA snapshot algorithm .................................................................................................................................. 12
S3.4 Flowchart of the FDA snapshot algorithm ....................................................................................................... 13
S3.5 Analyses of clinical events .............................................................................................................................. 14
S3.6 Definition of treatment change ........................................................................................................................ 14
S3.7 Testing multiple outcomes .............................................................................................................................. 14
S3.8 Impact of COVID-19 ........................................................................................................................................ 15
S4 Dolutegravir dosing throughout ODYSSEY ........................................................................................................ 16
Table S4.1 Dolutegravir dosing in ODYSSEY main trial participants by Protocol Version ......................................... 16
Table S4.2 Dolutegravir dosing in ODYSSEY PK sub-study participants by Protocol Version .................................. 17
S5 Enrolment and eligibility ...................................................................................................................................... 18
Figure S5.1 ODYSSEY total population CONSORT diagram ..................................................................................... 18
Figure S5.2 ODYSSEY A CONSORT diagram ........................................................................................................... 19
Figure S5.3 ODYSSEY B CONSORT diagram ........................................................................................................... 20
S6 Baseline demographics ....................................................................................................................................... 21
Table S6.1 Baseline characteristics ............................................................................................................................ 21
Table S6.2 Baseline characteristics: Antiretroviral exposure [ODYSSEY B only] ...................................................... 25
S7 Efficacy ................................................................................................................................................................ 26
Table S7.1 Comparison of proportion with clinical or virological failure by 48 weeks ................................................. 26
Table S7.2 Incidence of clinical or virological failure by 48 weeks .............................................................................. 26
Table S7.3 Primary analysis of primary endpoint: Comparison of proportion with clinical or virological failure by 96
weeks ........................................................................................................................................................................... 27
Table S7.4 Incidence of clinical or virological failure by 96 weeks (alternative approach to analysis of primary
endpoint) ...................................................................................................................................................................... 27
Table S7.5 Comparison of proportion with clinical or virological failure by 144 weeks ............................................... 28
Table S7.6 Incidence of clinical or virological failure by 144 weeks ............................................................................ 28
Figure S7.1 Kaplan Meier: Time from randomisation to clinical or virological failure by 144 weeks .......................... 29
Table S7.7 Comparison of proportion of participants with HIV-1 RNA <50c/ml at 48 weeks ..................................... 30
Table S7.8 Comparison of proportion of participants with HIV-1 RNA <400c/ml at 48 weeks ................................... 30
Table S7.9 Comparison of proportion of participants with HIV-1 RNA <50c/ml at 96 weeks ..................................... 30
Table S7.10 Comparison of proportion of participants with HIV-1 RNA <400c/ml at 96 weeks ................................. 31
Table S7.11 FDA snapshot algorithm - comparison of proportion of participants with HIV-1 RNA <50 c/ml and >=50
c/ml at 48 weeks .......................................................................................................................................................... 31
2
Table S7.12 FDA snapshot algorithm - comparison of proportion of participants with HIV-1 RNA <400 c/ml and
>=400 c/ml at 48 weeks ............................................................................................................................................... 32
Table S7.13 FDA snapshot algorithm - comparison of proportion of participants with HIV-1 RNA <50 c/ml and >=50
c/ml at 96 weeks .......................................................................................................................................................... 32
Table S7.14 FDA snapshot algorithm - comparison of proportion of participants with HIV-1 RNA <400 c/ml and
>=400 c/ml at 96 weeks ............................................................................................................................................... 33
Figure S7.2 Per-protocol analysis ............................................................................................................................... 34
Figure S7.3 Secondary analysis: excluding participants in SOC arm initiating integrase inhibitor ............................. 35
Figure S7.4 Secondary analysis: per-protocol and excluding participants in SOC arm initiating integrase inhibitor .. 36
Figure S7.5 Sensitivity analysis: censoring at time of ART switch for treatment failure before confirmatory viral load
..................................................................................................................................................................................... 37
Figure S7.6 Sensitivity analysis: date of failure at confirmed VL>=400c/ml ............................................................... 38
Figure S7.7 Sensitivity analysis: date of failure at first VL>=400c/ml.......................................................................... 39
Figure S7.8 Analysis of the primary endpoint adjusted for baseline viral load or baseline CD4 ................................. 40
Table S7.15 Total population - Subgroup analyses for primary endpoint ................................................................... 41
Table S7.16 ODYSSEY A - Subgroup analyses for primary endpoint ........................................................................ 42
Table S7.17 ODYSSEY B - Subgroup analyses for primary endpoint ........................................................................ 43
Figure S7.9 Subgroup analysis: Treatment effects stratified by calendar time of DTG dose increases ..................... 44
Table S7.18 Rate of clinical events to trial censoring date: WHO 4, severe WHO 3 and death ................................. 45
Table S7.19 Rate of clinical events to week 96: WHO 4, severe WHO 3 and death .................................................. 46
Table S7.20 Details of WHO 3 (Severe) or 4 events or deaths during follow-up (until trial censoring date) .............. 48
Table S7.21 Treatment emergent resistance mutations post-failure in participants exposed to drug-class............... 49
S8 Immunology ......................................................................................................................................................... 50
Table S8.1 Total population - Changes in CD4 count over follow-up ......................................................................... 50
Table S8.2 ODYSSEY A - changes in CD4 count over follow-up ............................................................................... 50
Table S8.3 ODYSSEY B - changes in CD4 count over follow-up ............................................................................... 50
Figure S8.1 Total population - Changes in CD4 count over follow-up ........................................................................ 51
Figure S8.2 ODYSSEY A - changes in CD4 count over follow-up .............................................................................. 52
Figure S8.3 ODYSSEY B - changes in CD4 count over follow-up .............................................................................. 53
Table S8.4 Total population - Changes in CD4 percentage over follow-up ................................................................ 53
Table S8.5 ODYSSEY A - changes in CD4 percentage over follow-up ...................................................................... 54
Table S8.6 ODYSSEY B - changes in CD4 percentage over follow-up ...................................................................... 54
Figure S8.4 Total population - Changes in CD4 percentage over follow-up ............................................................... 55
Figure S8.5 ODYSSEY A - changes in CD4 percentage over follow-up .................................................................... 56
Figure 8.6 ODYSSEY B - changes in CD4 percentage over follow-up ....................................................................... 57
Table S8.7 Total population - Changes in CD4/CD8 ratio over follow-up ................................................................... 57
Table S8.8 ODYSSEY A - changes in CD4/CD8 ratio over follow-up......................................................................... 58
Table S8.9 ODYSSEY B - changes in CD4/CD8 ratio over follow-up......................................................................... 58
Figure S8.7 Total population - Changes in CD4/CD8 ratio over follow-up .................................................................. 59
Figure S8.8 ODYSSEY A - changes in CD4/CD8 ratio over follow-up ....................................................................... 60
Figure S8.9 ODYSSEY B - changes in CD4/CD8 ratio over follow-up ....................................................................... 61
3
S9 Lipids ................................................................................................................................................................... 62
Table S9.1 Total population - Total cholesterol changes over follow-up .................................................................... 62
Table S9.2 ODYSSEY A - Total cholesterol changes over follow-up ......................................................................... 62
Table S9.3 ODYSSEY B - Total cholesterol changes over follow-up ......................................................................... 62
Figure S9.1Total population - changes in Total cholesterol over follow-up ................................................................ 63
Figure S9.2 ODYSSEY A - changes in Total cholesterol over follow-up .................................................................... 64
Figure S9.3 ODYSSEY B - changes in Total cholesterol over follow-up .................................................................... 65
Table S9.4 Total population - LDL cholesterol changes over follow-up ...................................................................... 65
Table S9.5 ODYSSEY A - LDL cholesterol changes over follow-up ........................................................................... 66
Table S9.6 ODYSSEY B - LDL cholesterol changes over follow-up ........................................................................... 66
Figure S9.4 Total population - changes in LDL cholesterol over follow-up ................................................................. 67
Figure S9.5 ODYSSEY A - changes in LDL cholesterol over follow-up ...................................................................... 68
Figure S9.6 ODYSSEY B - changes in LDL cholesterol over follow-up ...................................................................... 69
Table S9.7 Total population - HDL cholesterol changes over follow-up ..................................................................... 69
Table S9.8 ODYSSEY A - HDL cholesterol changes over follow-up .......................................................................... 70
Table S9.9 ODYSSEY B - HDL cholesterol changes over follow-up .......................................................................... 70
Figure S9.7 Total population - changes in HDL cholesterol over follow-up ................................................................ 71
Figure S9.8 ODYSSEY A - changes in HDL cholesterol over follow-up ..................................................................... 72
Figure S9.9 ODYSSEY B - changes in HDL cholesterol over follow-up ..................................................................... 73
Table S9.10 Total population - Triglycerides changes over follow-up......................................................................... 73
Table S9.11 ODYSSEY A - Triglycerides changes over follow-up ............................................................................. 74
Table S9.12 ODYSSEY B - Triglycerides changes over follow-up ............................................................................. 74
Figure S9.10 Total population - changes in Triglycerides over follow-up ................................................................... 75
Figure S9.11 ODYSSEY A - changes in Triglycerides over follow-up ........................................................................ 76
Figure S9.12 ODYSSEY B - changes in Triglycerides over follow-up ........................................................................ 77
S 10 Adverse events.................................................................................................................................................... 78
Table S10.1 Serious Adverse Events (SAEs) to trial censoring date by SAE type* ................................................... 78
Table S10.2 Serious Adverse Events to trial censoring date ...................................................................................... 78
Table S10.3 Grade 3 or above clinical and laboratory adverse events to trial censoring date ................................... 81
Table S10.4 Adverse events leading to ART modification (any grade) to trial censoring date ................................... 84
Table S10.5 Serious Adverse Events (SAEs) to week 96 by SAE type* .................................................................... 85
Table S10.6 Serious Adverse Events to week 96 ....................................................................................................... 86
Table S10.7 Grade 3 or above clinical and laboratory adverse events to week 96 .................................................... 88
Table S10.8 Adverse events leading to ART modification (any grade) to week 96 .................................................... 91
S 11 Patient reported outcomes .................................................................................................................................. 93
-up ......................................................................... 93
Table S11.2 Summary of carer/self-reported adherence ............................................................................................ 93
Table S11.3 Summary of carer/self-reported acceptability of treatment during follow-up .......................................... 94
S 12 Antiretroviral therapy ........................................................................................................................................... 96
Table S12.1 Summary of initial ART regimens ........................................................................................................... 96
4
Table S12.2 Summary of substitutions and changes to initial ART regimens (to trial censoring date) ...................... 96
Table S12.3 Summary of substitutions and changes to initial ART regimens (to week 96) ....................................... 98
S 13 Safety data by DTG dose .................................................................................................................................. 100
Table S13.1 Summary of adverse events frequency and rates by DTG dose .......................................................... 100
S 14 Anthropometric measures ................................................................................................................................. 101
Table S14.1 Total population - Height (cm) change over follow-up .......................................................................... 101
Table S14.2 ODYSSEY A - Height (cm) change over follow-up ............................................................................... 101
Table S14.3 ODYSSEY B - Height (cm) change over follow-up ............................................................................... 102
Figure S14.1 Total population - Height (cm) change over follow-up ......................................................................... 103
Figure S14.2 ODYSSEY A - Height (cm) change over follow-up .............................................................................. 104
Figure S14.3 ODYSSEY B - Height (cm) change over follow-up .............................................................................. 105
Table S14.4 Total population - Weight (kg) change over follow-up .......................................................................... 105
Table S14.5 ODYSSEY A - Weight (kg) change over follow-up ............................................................................... 106
Table S14.6 ODYSSEY B - Weight (kg) change over follow-up ............................................................................... 106
Figure S14.4 Total population - Weight (kg) change over follow-up ......................................................................... 108
Figure S14.5 ODYSSEY A - Weight (kg) change over follow-up .............................................................................. 109
Figure S14.6 ODYSSEY B - Weight (kg) change over follow-up .............................................................................. 110
Table S14.7 Total population - BMI-for-age change over follow-up .......................................................................... 110
Table S14.8 ODYSSEY A - BMI-for-age change over follow-up ............................................................................... 111
Table S14.9 ODYSSEY B - BMI-for-age change over follow-up ............................................................................... 111
Figure S14.7 Total population - BMI-for-age change over follow-up......................................................................... 113
Figure S14.8 ODYSSEY A - BMI-for-age change over follow-up ............................................................................. 114
Figure S14.9 ODYSSEY B - BMI-for-age change over follow-up ............................................................................. 115
S 15 Biochemistry ...................................................................................................................................................... 116
Table S15.1 Total population - Creatinine changes over follow-up........................................................................... 116
Table S15.2 ODYSSEY A - Creatinine over follow-up .............................................................................................. 116
Table S15.3 ODYSSEY B - Creatinine over follow-up .............................................................................................. 116
Figure S15.1 Total population - Creatinine changes over follow-up ......................................................................... 117
Figure S15.2 ODYSSEY A- Creatinine changes over follow-up ............................................................................... 118
Figure S15.3 ODYSSEY B- Creatinine changes over follow-up ............................................................................... 119
5
S 1 ODYSSEY Trial Team
Penta Foundation: Carlo Giaquinto, Tiziana Grossele, Daniel Gomez-Pena, Davide Bilardi, Giulio Vecchia
Clinical Trial Units
MRC CTU at UCL: Shabinah S. Ali, Abdel Babiker, Shazia Begum, Chiara Borg, Anne-Marie Borges Da Silva, Joanna
Calvert, Man Chan, Nimisha Dudakia, Deborah Ford, Joshua Gasa, Diana M. Gibb, Nasir Jamil, Sarah Lensen, Emma
Little, Fatima Mohamed, Samuel Montero, Cecilia L. Moore, Rachel Oguntimehin, Anna Parker, Reena Patel, Tasmin
Phillips, Tatiana Sarfati, Karen Scott, Clare Shakeshaft, Moira Spyer, Margaret Thomason, Anna Turkova, Rebecca
Turner, Nadine Van Looy, Ellen White, Ian White, Kaja Widuch, Helen Wilkes, Ben Wynne
INSERM SC-10-US19--ANRS: Alexandra Compagnucci, Yacine Saidi, Yoann Riault, Alexandra Coelho, Laura
Picault, Christelle Kouakam
PHPT: Tim R. Cressey, Suwalai Chalermpantmetagul, Dujrudee Chinwong, Gonzague Jourdain, Rukchanok
Peongjakta, Praornsuda Sukrakanchana, Wasna Sirirungsi
Trial sites
Joint Clinical Research Centre, Uganda: Cissy M. Kityo, Victor Musiime, Elizabeth Kaudha, Annet Nanduudu,
Emmanuel Mujyambere, Paul Ocitti Labeja, Charity Nankunda, Juliet Ategeka, Peter Erim, Collin Makanga, Esther
Nambi, Abbas Lugemwa, Lorna Atwine, Edridah Keminyeto, Deogratiuos Tukwasibwe, Shafic Makumbi, Emily
Ninsiima, Mercy Tukamushaba, Rogers Ankunda, Ian Natuhurira, Miriam Kasozi, Baker Rubinga, Diana Antonia
Rutebarika, Rashida Nazzinda, Shamim Nakabuye, Julius Tumusiime, Alice Mulindwa, Ritah Mbabazi, Milly
Ndigendawani, Edward Bagirigomwa, Eddie Rubanga, David Eram, Maria Nannungi, Chrispus Katemba, Disan
Mulima, Josephine Namusanje, Mariam Nabalamba, Priscilla Kyobutungi, Phyllis Mwesigwa Rubondo, Robinah
Kibenge, Claire Nasaazi, Basiimwa Roy Clark, Enock Babu, Alex Musiime, Faith Mbasani, Martin Ojok, Odoch Denis,
David Baliruno, Katabalwa Juliet, Ouma Benson, Barbara Ainebyona
Baylor College of Medic Adeodata R. Kekitiinwa, Pauline Amuge, Dickson

Bbuye, Justine Nalubwama, Winnie Akobye, Muzamil Nsibuka Kisekka, Anthony Kirabira, Gloria Ninsiima, Sylvia
Namanda, Gerald Agaba, Immaculate Nagawa, Annet Nalugo, Florence Namuli, Rose Kadhuba, Rachael Namuddu,
Lameck Kiyimba, Angella Baita, Eunice Atim, Olivia Kobusingye, Clementine Namajja, Africanus Byaruhanga, Rogers
Besigye, Herbert Murungi, Geoffrey Onen, Lawrence Lekku, Judith Tikabibamu
MUJHU Research Collaboration, Uganda: Philippa Musoke, Linda Barlow-Mosha, Grace Ahimbisibwe, Rosemary
Namwanje, Hajira Kataike, Mark Ssenyonga, Brenda Kakayi, Rebecca Sakwa, Sarah Nakabuye, Barbara Musoke
Nakirya, Gladys Kasangaki, Raymonds Kyambadde, David Balamusani, Winnie Nansamba, Stella Nalusiba,
Emmanuel Mayanja, Richard Isabirye, Erinah Kyomukama, Rebecca Wampamba, Mildred Kabasonga, Zaam Zinda
Nakawungu, Sarah Babirye, Olivia Kaboggoza, Juliet Nanyonjo, Joanita Nankya Baddokwaya, Alice Elwana, Winfred
Kaahwa, Bosco Kafufu, Emmanuel Hakiza, Maria Musisi, Paula Namayanja, Maria Gorreti Nakalema, Robert
Serunjogi, Monica Etima, Phionah Kibalama, Joel Maena, Agnes Mary Mugagga, Annet Miwanda, Monica Nolan.
UZCRC, Zimbabwe: James Hakim, Hilda Mujuru, Kusum Nathoo, Mutsa Bwakura-Dangarembizi, Ennie Chidziva,
Shepherd Mudzingwa, Secrecy Gondo, Godfrey Musoro, Vivian Mumbiro, Gloria Tinago, Shirley Mutsai, Joy
Chimanzi, Columbus Moyo, Ruth Nhema, Misheck Nkalo Phiri, Stuart Chitongo, Joshua Choga, Joyline Bhiri, Wilber
Ishemunyoro, Makhosonke Ndlovu, Moses Chitsamatanga, Pia Ngwaru, Tsitsi Gwenzi, Wendy Mapfumo, Dorothy
Murungu, Trust Mukanganiki, Prosper Dube, Tapiwa Gwaze, Farai Matimba, Tawona Mudzviti, Zivai
Mupambireyi, Sibusisiwe Weza, Cleopatra Langa, Sandra Musarurwa, Shamiso Gwande
FAM-CRU, South Africa: Mark F. Cotton, Anita Janse van Rensburg, Marlize Smuts, Catherine Andrea, Sumaya
Dadan, Sonja Pieterse, Vinesh Jeaven, Candice Makola, George Fourie, Kurt Smith, Els Dobbels, Peter Zuidewind,
Hesti Van Huyssteen, Mornay Isaacs, Georgina Nentsa, Thabisa Ncgaba, Candice MacDonald, Maria Bester, Wilma
Orange, Ronelle Arendze, Mark Mulder, Lucille Malgraaf, Ashley Harley.
PHRU, South Africa: Avy Violari, Nastassja Ramsagar, Afaaf Liberty, Ruth Mathiba, Mandisa Nyati, Haseena
Cassim, Lindiwe Maseko, Nkata Kekane, Busi Khumalo, Mirriam Khunene, Noshalaza Sbisi, Jackie Brown, Tryphina
Madonsela, Nokuthula Mbadaliga, Zaakirah Essack, Reshma Lakha, Aasia Vadee, Derusha Frank, Nazim Akoojee,
Maletsatsi Monametsi, Gladness Machache, Yolandie Fourie, Anusha Nanan-kanjee, Juan Erasmus, Angelous
Mamiane, Tseleng Daniel, Fatima Mayat, Nomfundo Maduna, Patsy Baliram, Sibongile Sithebe, Emily Lebotsa,
Siphiwe Mkhize
6
Klerksdorp Tshepong Hospital Complex, South Africa: Ebrahim Variava, Modiehi Rakgokong, Dihedile
Scheppers, Tumelo Moloantoa, Abdul Hamid Kaka, Tshepiso Masienyane, Akshmi Ori, Kgosimang Mmolawa,
Pattamukkil Abraham.
Durban International Clinical Research Site, South Africa: Moherndran Archary, Rosie Mngqibisa, Rejoice Mosia,
Sajeeda Mawlana, Rashina Nundlal, Penelope Madlala, Allemah Naidoo, Sphiwee Cebekhulu, Petronelle Casey,
Subashinie Sidhoo, Minenhle Chikowore, Lungile Nyantsa, Sheleika Singh
AHRI, South Africa: Nigel Klein, Osee Behuhuma, Olivier Koole, Kristien Bird, Nomzamo Buthelezi, Mumsy
Mthethwa, Gugu Gasa, Siva Danaviah and Theresa Smit
PHPT CTU: Tim R. Cressey, Suwalai Chalermpantmetagul, Gonzague Jourdain, Nicole Ngo Giang Huong, Dujrudee
Chinwong, Chalermpong Saenjum, Rukchanok Peongjakta, Pra-ornsuda Sukrakanchana, Woottichai Khamduang,
Laddawan Laomanit, Ampika Kaewbundit, Jiraporn Khamkon, Kanchana Than-in-at, Sanupong Chailert, Worathip
Sripaoraya, Nitinart.krueduangkam, Namthip Kruenual, Warunee Khamjakkaew, Soraya Klinprung, Prapokklao
Hospital: Chaiwat Ngampiyaskul, Pisut Greetanukroh, Praechadaporn Khannak, Pathanee Tearsansern, Wanna
Chamjamrat, Phayao Hospital, Thailand: Nuttawat Chanto, Thitiwat Thapwai, Khanungnit Thungkham, Patcharee
Puangmalai, Chutima Ruklao, Chiangrai Prachanukroh Hospital, Thailand: Pradthana Ounchanum, Suwimon
Khusuwan, Sukanda Denjanta, Yupawan Thaweesombat, Jutarat Thewsoongnoen, Kanyanee Kaewmamueng,
Phakamas Kamboua, Supawadee Pongprapass (Sangjan), Warunee Srisuk, Areerat Kongponoi, Juthamas
Limplertjareanwanich, Nakornping Hospital, Thailand: Suparat Kanjanavanit, Prattana Leenasirimakul, Chayakorn
Saewtrakool, Pacharaporn Yingyong, Duangrat Chutima (Suwan), Rangwit Junkaew, Orapin Khatngam, Thannapat
Chankun, Khon Kaen Hospital, Thailand: Ussanee Srirompotong, Patamawadee Sudsaard, Sookpanee
Wimonklang, Turian Petpranee, Mahasarakam Hospital, Thailand: Sathaporn Na-Rajsima, Pattira Runarassamee,
Nuananong Kunjaroenrut, Arttasid Udomvised, Tassawan Khayanchoomnoom, Watchara Meethaisong, Ketmookda
Trairat
HIVNAT, Thailand: Thanyawee Puthanakit, Suvaporn Anugulruengkitt, Wipaporn Natalie Songtaweesin, Torsak
Bunupuradah, Naruporn Kasipong, Sararut Chanthaburanun, Apicha Mahanontharit, Kesdao Nanthapisal, Thidarat
Jupimai, Thornthun Noppakaorattanamanee, Chutima Saisaengjan
European Site Investigators: Goethe University Frankfurt, Germany: Stephan Schultze-Strasser, Christoph Königs,
UKE Eppendorf, Germany: Robin Kobbe, Ulf Schulze-Sturm, Felicia Mantkowski, Cornelius Rau, Heartlands
Hospital, UK: Steve Welch, Jacqui Daglish, Laura Thrasyvoulou, Kate Gandhi, Yvonne Vaughan-Gordon, Great
Ormand Street Hospital, UK: Delane Singadia, Sophie Foxall, Judith Acero, Gosia Pasko-Szcech, Jacquie Flynn, St
Gareth Tudor-Williams, Farhana Abdulla, Caroline Foster, Sobia Mustafa, Leicester Royal
Infirmary, UK: Srini Bandi, Jin Li, Jackie Philps, Leeds General Infirmary, UK:
Richard Vowden, Maria Dowie Kings College Hospital, UK: Colin Ball Eniola Nsirim, Kathleen McClaughlin,
Hospital 12 de Octubre, Spain: India Garcia, Pablo Rojo Conejo, Cristina Epalza, Luis Prieto Tato, Maite Fernandez,
Luis Escosa Garcia, Hospital La Paz, Spain: Maria José Mellado Peña, Talia Sainz Costa, Hospital San Joan de
Déu, Spain: Claudia Fortuny Guasch, Antoni Noguera Julian, Carolina Estepa, Elena Bruno, Patricia Mendez Garcia,
Alba Murciano Cabeza, Biobanco Gregorio Maranon, Maria Angeles Muñoz Fernandez, Jose Luis Jimenez, Coral
Gomez Rico, Centro Materno-infantile do Norte, Portugal: Laura Marques, Carla Teixeira, Alexandre Fernandes,
Rosita Nunes, Helena Nascimento, Andreia Padrao, Joana Tuna, Helena Ramos, Ana Constança Mendes, Helena
Pinheiro, Ana Cristina Matos
Local Site Monitors: Flavia Kyomuhendo, Sarah Nakalanzi, Cynthia Mukisa Williams, Leora Sewnarain, Ntombenhle
Ngcobo, Deborah Pako, Nompumelelo Yende, Jacky Crisp, Marlize Smuts, Benedictor Dube, Precious Chandiwana,
Winnie Gozhora, Thidarat Jumpimai
Substudies
PK substudies: David Burger, Pauline Bollen, Angela Colbers, Hylke Waalewijn.
Virology-immunology substudy: Nigel Klein, Eleni Nastouli, Anita De Rossi, Maria Angeles Munoz Fernandez
Social Science substudy and Youth Trial Board project: Janet Seeley, Sarah Bernays, Stella Namukwaya, Zivai
Mupambireyi, Magda Conway
Trial Committees
Independent Trial Steering Committee Members: Ian Weller, Elaine Abrams, Tsitsi Apollo, Polly Clayden, Valériane
Leroy
7
Independent Data Monitoring Committee Members: Anton Pozniak, Jane Crawley, Rodolphe Thiébaut, Helen
McIlleron
Endpoint Review Committee Members: Alasdair Bamford, Hermione Lyall, Andrew Prendergast, Felicity Fitzgerald,
Anna Goodman
8
S 2 Primary and secondary outcome measures in ODYSSEY
Table S2.1 Primary and secondary outcome measures in ODYSSEY
Primary Efficacy Outcome
Difference in proportion with clinical or virological failure by 96 weeks, defined as the first occurrence of any of the following
components:
1.
with viral load <500c/mL at baseline) and switch to second/third line antiretroviral therapy for treatment failure
2. Virological failure (defined as a viral load of greater than or equal to 400 copies/mL at or after week 36 confirmed by the
next visit)
3. New or recurrent AIDS defining event (WHO 4) or severe WHO 3 event, confirmed by the Endpoint Review Committee
4. All-cause death
Secondary efficacy outcomes
Difference in proportion with clinical or virological failure (as defined above) by 48 weeks
Time to any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events, confirmed by the Endpoint Review
Committee
Proportion of children with Viral Load <50 c/ml at 48 and 96 weeks
Proportion of children with Viral Load <400 c/ml at 48 and 96 weeks
Rate of HIV-associated events (WHO 4 and severe WHO 3) and death over 96 weeks
Change in CD4 count and percentage and CD4/CD8 ratio from baseline to weeks 48 and 96
Proportion developing new resistance mutations
Secondary safety outcomes
Change in total cholesterol, triglycerides and lipid fractions (high-density lipoproteins, low-density lipoproteins) from baseline to
weeks 48 and 96 (change in total cholesterol from baseline to week 96 will be used to formally assess superiority of dolutegravir-
based regimen vs. standard-of-care)
Incidence of serious adverse events
Incidence of new clinical and laboratory grade 3 and 4 adverse events
Incidence of adverse events (of any grade) leading to treatment modification
Other secondary outcomes
Quality of life
Adherence and acceptability
9
S 3 Statistical methods
S3.1 Analysis populations
Intent-to-treat population
The intent-to-treat (ITT) population includes all randomised patients, except those considered randomised
in error. Randomisation in error was judged by whether the participant met a major violation of the eligibility
criteria, including the patient was randomised at a time when the dolutegravir dose was not known for the
-
randomisation follow-up.
Intent-to-treat analyses are performed on all patients in the ITT population and patients are analysed
according to the study group to which they were randomised.
The primary analysis includes participants randomised prior to the end of main trial recruitment date; these
Follow-up was censored on April 24 2020, when all
children reached 96 weeks follow-up.
Per protocol population
Participants who did not meet the eligibility criteria or where there was a major protocol deviation, e.g. site
prescribed incorrect drug, are excluded from this population. Changes to the third agent (i.e. the non-NRTI
component, including adding an additional third agent) for toxicity, failure or pregnancy are defined as a
change in therapy and participants are censored at this date. Any stop in regimen for >31 days is defined
as stopping therapy and participants are censored at this date.
S3.2 Primary endpoint

The primary outcome was the difference in the cumulative probability of virological or clinical failure by 96
weeks, estimated by Kaplan-Meier methods using time to the first occurrence of any of the following
components:
Insufficient virological response defined as <1 log10 drop at week 24 (or not <50 at week 24 if VL<500
at baseline) and switch to second/third-line treatment for treatment failure
Death due to any cause

Any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 event, confirmed by the
Endpoint Review Committee
The primary comparison was the DTG-based regimen versus SOC for the primary efficacy outcome in the
combined population (naïve and experienced) adjusted for stratification variables; subpopulation analyses
(ODYSSEY A and ODYSSEY B) were key secondary comparisons.
Handling viral load data
Participants were included in ODYSSEY both from sites where HIV RNA was routinely measured and from
sites where HIV RNA is not routinely measured. In the latter case, HIV RNA was measured retrospectively
on plasma samples stored at each clinic visit. Confirmatory HIV RNA measures were likely to be performed
faster in sites where HIV RNA monitoring occurred routinely. The primary endpoint included confirmed HIV
, the date of the next scheduled

vis
10
the confirmatory measure. Where a patient

failure without a confirmatory viral load before switch, the date of the next scheduled visit following the first
.
The primary endpoint included insufficient virological response by week 24, defined by less than a 1 log10
second/third line treatment for treatment failure. A participant was considered a failure if they switched to
second or third line treatment following insufficient virological response at week 24 without suppressing
(VL<50) between week 24 and switching therapy. Date of switching therapy was used as the primary
endpoint failure date.
Analysis details for primary efficacy outcome

The primary outcome was assessed by time to clinical or virological failure (ODYSSEY A and B combined)
using Kaplan Meier curves to estimate the proportion of children failing in each arm at any time up to the
week 96 censoring date (96 weeks from date of randomisation). The survival curve for each combination of
strata and randomised group was calculated using a Cox model adjusting for stratification factors and
randomised group. The average survival curve for each randomised group was estimated as a weighted
average of the corresponding stratum-specific survival curves, with weights proportional to the number of
individuals in each stratum across both randomised groups at baseline. The mean of these differences at
week 96 was the point estimate for the difference in overall survival function between DTG and SOC arm. A
two-sided 95% confidence interval for the proportion failing by treatment arm was estimated by bias
corrected bootstrap. A two sided bias-corrected 95% CI for the difference in proportions (DTG SOC) was
calculated with bootstrap standard errors. Bootstrapped standard errors for the risk difference were used;
bootstrapping was sampled 1000 times and stratified by stratification factors.
Further details in Statistical Analysis Plan.
Sensitivity analyses for primary endpoint

The following sensitivity analyses were performed for the primary endpoint:
i. c/ml, with a treatment switch for
ii. Using actual dates of confirmatory viral loads (or switch for treatment failure) for date of failure.
iii. /ml at or after 36 weeks for date of failure.
Per protocol and secondary analyses
*, by comparing the primary

endpoint between arms in the per protocol population (described above in S3.1).
In addition, we pre-specified a secondary analysis estimating the treatment effect, comparing treatment
with DTG to non-integrase SOC, for which we excluded participants in SOC who initiated an integrase
*Reference: ICH E9 (R1) addendum on estimands and sensitivity analysis in clinical trials to the guideline
on statistical principles for clinical trials. EMA/CHMP/ICH/436221/2017
Sub-group analyses
Sub-group analyses were pre-specified as follows:

i. Sex
ii. Age groups
11
iii. Weight bands
iv. Baseline HIV RNA
v. Baseline CD4 percent
vi. Routine availability at site of resistance tests for children failing treatment
vii. NRTI backbone
viii. bPI vs non-bPI SOC regimens*
ix. Calendar time**
*Data insufficient to perform this analysis due to strong association between bPI/non-bPI SOC regimens
and ODYSSEY A/ODYSSEY B
**This was pre-specified to explore the effect of any changes in eligibility criteria over time. In fact, there
was limited follow-up prior to opening recruitment to children weighing <20kg; and the main trial recruitment
completed before the cohort of children <14kg was recruited and this cohort is not included here. Instead,
we included a sub-group analysis based on calendar time corresponding to the timing of DTG dose
changes in the main trial.
S3.3 FDA snapshot algorithm

Definitions for FDA snapshot algorithm
The FDA snapshot algorithm in ODYSSEY was used to compare virological suppression (<50 c/ml and
<400 c/ml, indicated by Y) in DTG vs. SOC at weeks 48 and 96 (indicated by X).
Here we define changes to the initial ART regimen for the purposes of the FDA snapshot algorithm:
Strict initial regimen - the strict initial regimen assigned at randomisation to ODYSSEY;
changes to NRTI backbone for increases in age/weight, simplification
(including patient/carer decisions), and drug availability. Changes to 3rd agent are ignored when: (1)
DTG arm changes to the DTG dose for increases in age/weight; (2) SOC arm - changes to 3rd
agent for simplification (including patient/carer decision), drug availability, and increases in weight.
include: changes to NRTI backbone for any reason other than those
listed above and treatment failure.
- include: (i) changes to the NRTI backbone in the initial regimen for
treatment failure; (ii) changes to the third agent for treatment failure; (iii) changes to third agent for
Only post-baseline and on-treatment viral loads were used in the algorithm. Participants interrupting ART
prior to or within week X window were assumed to remain on the regimen and were treated as a treatment
switch when a new regimen (according to rules above) was initiated (although, viral loads off treatment
were not used). In the case where a participant had multiple viral loads within week X window, the latest
viral load was used in the FDA snapshot algorithm, provided it was on/prior to trial censoring date (24 April
2020).
12
S3.4 Flowchart of the FDA snapshot algorithm
Was there at least one viral load*

that met both the following
conditions:
Yes (1) Within week X window, and No
(2) Prior to/at change to
permitted/non-permitted
ART, LTFU or death?
Did the participant switch

Was to permitted/non-permitted
last viral load within ART, die or become LTFU
week X window <Y prior to end of week X
c/ml? window?
No
Yes
Yes No
Did the participant switch

to non-permitted ART for a
reason other than toxicity?
Yes
No
Did the participant die or switch

to non-permitted ART due to
No toxicity prior to end of week X
window?
Was the last viral load Yes

prior to ART switch or
LTFU <Y c/ml or
missing?
HIV-RNA No
<Y c/ml
Yes
HIV-RNA
Missing Missing virological Missing virological
virological data in data in window on data in window on
window on non-permitted ART initial regimen but
permitted ART for due to toxicity or missing viral load in
other reasons or participant died week X window
LTFU while VL<Y
c/ml
*Off ART viral loads will be excluded from algorithm.
13
S3.5 Analyses of clinical events
Clinical events (WHO severe stage 3 and stage 4 events and adverse events) were compared between
arms using the hazard ratio for first event from a Cox proportional hazards regression model (adjusted for
stratification factors).
S3.6 Definition of treatment change

The following are used to define substitutions and changes to initial ART regimens (Appendix, S12):
A strict initial regimen was defined as strictly the regimen allocated at trial entry.
A substituted initial regimen was defined as the strict initial regimen allowing for substitutions to the third
agent of the regimen for reasons other than toxicity, treatment failure, pregnancy or major protocol
deviation (e.g. site prescribing incorrect drug) or to the NRTI component for any reason. Permissible
substitutions to the third agent included reasons for simplification, drug availability, patient/carer decision
and increases in weight.
All reductions to NRTIs were also considered substituted initial regimen.
All changes to the third agent not defined above as a substitution to the initial regimen were considered a
change from the initial treatment regimen. In the DTG arm, DTG should only be stopped for toxicity, failure
Changes to the third agent for reasons of treatment failure were defined as switching to second line therapy
in ODYSSEY A or third line therapy in ODYSSEY B.
Any interruptions or reductions to a regimen for less than or equal to 31 consecutive days were allowed; as
long as the total number of drugs allocated in the regimen was not increased.
A stop to the initial regimen occurred when a patient interrupted their regimen or their third agent for >31
days.
S3.7 Testing multiple outcomes

In accordance with the statistical analysis plan, we have made no adjustment to p-values or confidence
intervals to allow for testing multiple secondary outcomes.
Statistical analysis plan (version 5.0) describes the following:
The ODYSSEY primary outcome is a composite outcome of virological failure, clinical events (WHO 4 and
severe WHO 3 events) and death. The primary analysis is non-inferiority of DTG versus SOC. If the 95% CI
for the treatment effect (difference in proportion failing by 96 weeks (DTG-SOC)) lies below the non-
inferiority margin, then we will also test for superiority; because this is a closed test procedure there is no
issue of multiplicity.
Secondary outcomes are divided in the protocol into efficacy outcomes, safety outcomes and other patient-
reported outcomes. For safety outcomes it is appropriate to test each independently since it is important to
identify any risks associated with DTG. Change in total cholesterol from baseline to week 96 has been
defined as the primary safety outcome for the assessment of superiority of DTG versus SOC.
The secondary efficacy outcomes are mostly components of the primary outcome or very closely related to
the primary outcome (virological and clinical outcomes). We will not adjust for multiple testing for these
since they are correlated with the primary outcome (so standard adjustments are conservative). Resistance
and immunological outcomes are considered exploratory and significance tests on these outcomes alone
will not be used to conclude superiority.
14
We will report significance tests for differences between treatment arms for patient-reported outcomes, but
if we have failed to demonstrate non-inferiority of DTG versus SOC for the primary outcome, we will not use
significance tests for these patient-reported outcomes to conclude superiority.
S3.8 Impact of COVID-19

Due to the COVID-19 pandemic (March 2020 onwards), and uncertainty about how it would evolve and
ability of clinics to conduct face-to-face visits, sites were advised they could conduct end of randomised
phase visits for the main trial outside of the pre-defined window (24th April 2020 (96 weeks from date last
30 June 2020) for participants who had completed 96 weeks follow-up. Three
were seen early and exited the trial before the last child reached 96 weeks (trial week at exit: 114, 165 and
174).
There was a slight excess of missed visits between 1st March and 24th April 2020; 10% of expected visits
were missed over this period compared to 1-3% over the remainder of trial follow-up. Missed visits were
similar in both arms (DTG 10%; SOC 10%) and the majority of participants (45/46) were post 96 weeks
follow-up. 28/46 participants who missed a visit in this period were seen subsequently; of the remainder, 15
had been lost to follow-up by the end of October 2019 and 3 were lost to follow-up after end of November
2019 (last seen at visit weeks 96, 132, 156 respectively). In addition, 35 participants missed a visit in
person during this period and completed their visit over the phone (samples for viral load testing were not
taken but continuity of ART supply was ensured); 34/35 participants were post 96 weeks follow-up at their
phone visit. 34/35 participants were seen subsequently.
15
S 4 Dolutegravir dosing throughout ODYSSEY

Table S4.1 Dolutegravir dosing in ODYSSEY main trial participants by Protocol Version
ODYSSEY v2.0¤ ODYSSEY v3.0 ODYSSEY v4.0 ODYSSEY v5.0/v6.0
WHO weight-band FDA approval* EMA approval**
(Sep 2016 onwards) (Mar 2017 onwards) (May 2018 onwards) (May 2019/Feb 2020 onwards)
3 to <6kg - - - -
6 to <10kg - - - -
10 to <14kg - - - -
14 to <20kg 20mg¥ Feb-2017 25mg FCT 25mg DT§ 25mg DT
20 to <25kg 25mg Feb-2017 25mg FCT 25mg FCT 25mg FCT 30mg DT or 50mg FCT§ 50mg FCT
25 to <30kg 25mg Feb-2017 25mg FCT 25mg FCT 50mg FCT 25mg FCT 50mg FCT 50mg FCT
30 to <35kg 35mg Jun-2016 35mg Feb-2017 35mg FCT 35mg FCT 50mg FCT 35mg FCT 50mg FCT 50mg FCT
35 to <40kg 35mg Jun-2016 35mg Feb-2017 35mg FCT 35mg FCT 50mg FCT 35mg FCT 50mg FCT 50mg FCT
50mg Aug-2013 50mg Jan-2014 50mg FCT 50mg FCT 50mg FCT 50mg FCT
age restriction removed Jun 2016
¥ 20mg FCT approved by EMA in children weighing 15 to <20kg only

in children weighing 15 to <20kg only
following protocol version 3.0 and above were recommended to increase the DTG dose of children 25 to <40kg to 50mg FCT QD at their
next scheduled study visit based on the results of the weight-band pharmacokinetic sub-study.
§ Protocol version 4.0 also allowed for the adjustment of weight-band dose based on findings from the ongoing weight-band pharmacokinetic sub-study with ethics notification
¤ Protocol version 1.0 was not used
Abbreviations: FCT=Film-coated tablets; DT=Dispersible tablets; v=Version.
16
Table S4.2 Dolutegravir dosing in ODYSSEY PK sub-study participants by Protocol Version
WHO weight-band Initiated under Protocol v3.0 Initiated under Protocol v4.0
3 to <6kg - Single PK Curve on 5mg or 10mg DT*
6 to <10kg - Single PK Curve on 15mg DT
10 to <14kg - Single PK Curve on 20mg DT
14 to <20kg Single PK Curve on 25mg FCT Single PK Curve on 25mg DT
20 to <25kg Single PK Curve on 25mg FCT Single PK Curve on 30mg DT or 50mg FCT
25 to <30kg Cross-over PK with one curve on 25mg FCT and second curve on 50mg FCT -
- -
*DTG dose for infants 3-<6kg is dependent on age: infants <6 months of age received d DTG 10mg QD, both as dispersible tablets
25mg FCT initiated under protocol version 3.0
Abbreviations: FCT=Film-coated tablets; DT=Dispersible tablets; v=Version; PK=Pharmacokinetic.
17
S 5 Enrolment and eligibility

Figure S5.1 ODYSSEY total population CONSORT diagram
819 children assessed for eligibility
109 determined ineligible:

102 failed at least one eligibility criteria
3 did not return in window
4 other reasons+
710 underwent randomization
3 children randomized in error:

1 not ART naive (ODYSSEY A)
2 randomized prior to DTG availability for
weight
350 assigned to dolutegravir arm (DTG) 357 assigned to standard-of-care arm (SOC)
5 LTFU prior to week 96 and prior to meeting primary 15 LTFU prior to week 96 and prior to meeting primary
endpoint endpoint
2 withdrawn 9 withdrawn
3 LTFU 6 LTFU
16 LTFU prior to trial censoring date and prior to 21 LTFU prior to trial censoring date and prior to
meeting primary endpoint meeting primary endpoint
8 LTFU 7 LTFU
2 completed end of randomised phase visit prior to trial 1 completed end of randomised phase visit prior to trial
censoring date* censoring date*
350 included in analyses** 357 included in analyses**
band. One patient had a proposed second-line ART drug (etravirine) which was unavailable.
*Due to the COVID-19 pandemic, sites were advised they could conduct end of randomised phase visits prior to trial
censoring date, provided the participant had reached 96 weeks.
**All participants contribute to the primary endpoint (further details in Statistical Methods section of appendix, S3.2).
18
Figure S5.2 ODYSSEY A CONSORT diagram
3 other reasons+
2 children excluded for major ineligibility:

1 not ART naive
-weight
endpoint endpoint
2 LTFU 4 LTFU
12 LTFU prior to trial censoring date and prior to meeting 14 LTFU prior to trial censoring date and prior to meeting
primary endpoint primary endpoint
7 LTFU 5 LTFU
2 completed end of randomized phase visit prior to trial 1 completed end of randomized phase visit prior to trial
censoring date* ----censoring date*
band.
*Due to the COVID-19 pandemic, sites were advised they could conduct end of randomised phase visits prior to trial
censoring date.
19
Figure S5.3 ODYSSEY B CONSORT diagram
1 other reasons+
1 child excluded for major ineligibility:

-weight
endpoint endpoint
1 LTFU 2 LTFU
4 LTFU prior to trial censoring date and prior to meeting 7 LTFU prior to trial censoring date and prior to meeting
primary endpoint primary endpoint
1 LTFU 2 LTFU
+One patient had a proposed second-line ART drug (etravirine) which was unavailable.
20
S 6 Baseline demographics
Table S6.1 Baseline characteristics
Total A B
DTG SOC Total DTG SOC Total DTG SOC Total
Participants 350 357 707 154 157 311 196 200 396
randomised
Country
Germany 5 ( 1%) 3 ( 1%) 8 ( 1%) 5 ( 3%) 2 ( 1%) 7 ( 2%) 0 ( 0%) 1 ( 1%) 1 ( 0%)
Portugal 1 ( 0%) 0 ( 0%) 1 ( 0%) 1 ( 1%) 0 ( 0%) 1 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0%)
South Africa 61 (17%) 83 (23%) 144 (20%) 36 (23%) 41 (26%) 77 (25%) 25 (13%) 42 (21%) 67 (17%)
Spain 3 ( 1%) 5 ( 1%) 8 ( 1%) 1 ( 1%) 3 ( 2%) 4 ( 1%) 2 ( 1%) 2 ( 1%) 4 ( 1%)
Thailand 28 ( 8%) 33 ( 9%) 61 ( 9%) 24 (16%) 26 (17%) 50 (16%) 4 ( 2%) 7 ( 4%) 11 ( 3%)
Uganda 170 (49%) 161 (45%) 331 (47%) 46 (30%) 53 (34%) 99 (32%) 124 (63%) 108 (54%) 232 (59%)
United Kingdom 3 ( 1%) 5 ( 1%) 8 ( 1%) 2 ( 1%) 4 ( 3%) 6 ( 2%) 1 ( 1%) 1 ( 1%) 2 ( 1%)
Zimbabwe 79 (23%) 67 (19%) 146 (21%) 39 (25%) 28 (18%) 67 (22%) 40 (20%) 39 (20%) 79 (20%)
Sex
male 176 (50%) 186 (52%) 362 (51%) 67 (44%) 80 (51%) 147 (47%) 109 (56%) 106 (53%) 215 (54%)
female 174 (50%) 171 (48%) 345 (49%) 87 (56%) 77 (49%) 164 (53%) 87 (44%) 94 (47%) 181 (46%)
Age at last
birthday (years)
n 350 357 707 154 157 311 196 200 396
mean (SD) 12.1 (3.6) 11.8 (3.5) 12.0 (3.5) 11.8 (3.5) 11.6 (3.8) 11.7 (3.6) 12.3 (3.6) 12.0 (3.3) 12.2 (3.5)
median 12.2 12.1 12.2 11.9 11.5 11.8 12.9 12.5 12.6
[IQR] [9.2, 15.1] [8.8, 14.7] [9.1, 14.9] [9.2, 14.9] [8.5, 15.0] [8.8, 14.9] [9.2, 15.3] [9.4, 14.6] [9.3, 14.9]
[range] [3.4-18.0] [2.9-18.0] [2.9-18.0] [3.4-17.8] [2.9-18.0] [2.9-18.0] [4.0-18.0] [4.0-18.0] [4.0-18.0]
2-<6years 15 ( 4%) 11 ( 3%) 26 ( 4%) 7 ( 5%) 5 ( 3%) 12 ( 4%) 8 ( 4%) 6 ( 3%) 14 ( 4%)
6-<12years 153 (44%) 164 (46%) 317 (45%) 72 (47%) 84 (54%) 156 (50%) 81 (41%) 80 (40%) 161 (41%)
12-<18years 182 (52%) 182 (51%) 364 (51%) 75 (49%) 68 (43%) 143 (46%) 107 (55%) 114 (57%) 221 (56%)
Weight (kg)
n 350 357 707 154 157 311 196 200 396
mean (SD) 34.1 (13.2) 33.8 (13.1) 34.0 (13.2) 34.5 (14.5) 34.2 (14.5) 34.3 (14.5) 33.7 (12.1) 33.6 (12.0) 33.6 (12.1)
median 30.4 31.0 30.7 30.0 29.6 29.7 30.4 31.9 31.4
[IQR] [23.7, 43.7] [23.3, 42.7] [23.4, 43.0] [23.4, 45.0] [22.8, 44.8] [23.2, 44.8] [23.8, 42.6] [23.4, 41.3] [23.8, 42.3]
[range] [14.0-85.0] [14.2-72.7] [14.0-85.0] [14.0-85.0] [14.2-72.7] [14.0-85.0] [14.2-71.5] [14.8-65.4] [14.2-71.5]
14-<20kg 39 (11%) 43 (12%) 82 (12%) 18 (12%) 20 (13%) 38 (12%) 21 (11%) 23 (12%) 44 (11%)
20-<25kg 71 (20%) 64 (18%) 135 (19%) 33 (21%) 29 (18%) 62 (20%) 38 (19%) 35 (18%) 73 (18%)
21
25-<30kg 58 (17%) 59 (17%) 117 (17%) 26 (17%) 32 (20%) 58 (19%) 32 (16%) 27 (14%) 59 (15%)
30-<35kg 38 (11%) 51 (14%) 89 (13%) 16 (10%) 17 (11%) 33 (11%) 22 (11%) 34 (17%) 56 (14%)
35-<40kg 29 ( 8%) 32 ( 9%) 61 ( 9%) 12 ( 8%) 10 ( 6%) 22 ( 7%) 17 ( 9%) 22 (11%) 39 (10%)
>=40kg 115 (33%) 108 (30%) 223 (32%) 49 (32%) 49 (31%) 98 (32%) 66 (34%) 59 (30%) 125 (32%)
Height (cm)
n 350 357 707 154 157 311 196 200 396
mean (SD) 139.0 (18.3) 138.1 (18.2) 138.5 (18.2) 138.6 (19.4) 138.4 (20.2) 138.5 (19.8) 139.2 (17.4) 137.9 (16.6) 138.6 (17.0)
median 138.0 138.0 138.0 135.8 136.8 136.2 138.8 139.0 139.0
[IQR] [124.9, 154.5] [125.0, 151.0] [124.9, 152.5] [124.1, 155.0] [123.2, 152.4] [123.6, 154.0] [126.2, 154.1] [126.0, 149.7] [126.0, 152.0]
[range] [89.0-181.9] [91.0-179.6] [89.0-181.9] [89.0-181.9] [91.0-179.6] [89.0-181.9] [100.4-180.0] [98.0-177.1] [98.0-180.0]
BMI-for-Age*
n 350 357 707 154 157 311 196 200 396
mean (SD) -0.8 (1.2) -0.7 (1.2) -0.7 (1.2) -0.6 (1.2) -0.6 (1.2) -0.6 (1.2) -0.9 (1.1) -0.7 (1.1) -0.8 (1.1)
median -0.6 -0.6 -0.6 -0.5 -0.6 -0.5 -0.8 -0.6 -0.7
[IQR] [-1.4, 0.0] [-1.4, 0.1] [-1.4, 0.1] [-1.2, 0.2] [-1.5, 0.4] [-1.4, 0.3] [-1.5, -0.1] [-1.3, -0.0] [-1.4, -0.1]
[range] [-4.3-2.8] [-5.9-2.5] [-5.9-2.8] [-4.3-2.8] [-4.1-2.1] [-4.3-2.8] [-4.2-2.1] [-5.9-2.5] [-5.9-2.5]
<-3 22 ( 6%) 11 ( 3%) 33 ( 5%) 8 ( 5%) 4 ( 3%) 12 ( 4%) 14 ( 7%) 7 ( 4%) 21 ( 5%)
-3-<-2 20 ( 6%) 28 ( 8%) 48 ( 7%) 8 ( 5%) 16 (10%) 24 ( 8%) 12 ( 6%) 12 ( 6%) 24 ( 6%)
-2-<0 216 (62%) 219 (61%) 435 (62%) 91 (59%) 87 (55%) 178 (57%) 125 (64%) 132 (66%) 257 (65%)
>=0 92 (26%) 99 (28%) 191 (27%) 47 (31%) 50 (32%) 97 (31%) 45 (23%) 49 (25%) 94 (24%)
Mode of infection+
Mother to child 305 (87%) 300 (84%) 605 (86%) 123 (80%) 117 (75%) 240 (77%) 182 (93%) 183 (92%) 365 (92%)
Blood product 2 ( 1%) 1 ( 0%) 3 ( 0%) 0 ( 0%) 1 ( 1%) 1 ( 0%) 2 ( 1%) 0 ( 0%) 2 ( 1%)
Sexual contact 17 ( 5%) 22 ( 6%) 39 ( 6%) 17 (11%) 19 (12%) 36 (12%) 0 ( 0%) 3 ( 2%) 3 ( 1%)
Unknown 25 ( 7%) 33 ( 9%) 58 ( 8%) 13 ( 8%) 19 (12%) 32 (10%) 12 ( 6%) 14 ( 7%) 26 ( 7%)
Other 1 ( 0%) 1 ( 0%) 2 ( 0%) 1 ( 1%) 1 ( 1%) 2 ( 1%) 0 ( 0%) 0 ( 0%) 0 ( 0%)
Ethnic origin
White 5 ( 1%) 1 ( 0%) 6 ( 1%) 5 ( 3%) 0 ( 0%) 5 ( 2%) 0 ( 0%) 1 ( 1%) 1 ( 0%)
Black-African 310 (89%) 313 (88%) 623 (88%) 123 (80%) 126 (80%) 249 (80%) 187 (95%) 187 (94%) 374 (94%)
Black-other 1 ( 0%) 2 ( 1%) 3 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0%) 1 ( 1%) 2 ( 1%) 3 ( 1%)
Asian 28 ( 8%) 32 ( 9%) 60 ( 8%) 24 (16%) 26 (17%) 50 (16%) 4 ( 2%) 6 ( 3%) 10 ( 3%)
Mixed Black-White 3 ( 1%) 3 ( 1%) 6 ( 1%) 1 ( 1%) 1 ( 1%) 2 ( 1%) 2 ( 1%) 2 ( 1%) 4 ( 1%)
other 3 ( 1%) 6 ( 2%) 9 ( 1%) 1 ( 1%) 4 ( 3%) 5 ( 2%) 2 ( 1%) 2 ( 1%) 4 ( 1%)
CD4%**
n 350 357 707 154 157 311 196 200 396
mean (SD) 21 ( 13) 22 ( 12) 21 ( 13) 19 ( 11) 20 ( 12) 19 ( 12) 22 ( 14) 24 ( 12) 23 ( 13)
median 20 23 21 19 19 19 21 25 23
[IQR] [ 11, 29] [ 13, 31] [ 12, 30] [ 12, 28] [ 10, 28] [ 11, 28] [ 10, 32] [ 15, 33] [ 13, 33]
[range] [ 0- 59] [ 1- 70] [ 0- 70] [ 1- 50] [ 1- 70] [ 1- 70] [ 0- 59] [ 1- 51] [ 0- 59]
<10 80 (23%) 68 (19%) 148 (21%) 34 (22%) 38 (24%) 72 (23%) 46 (23%) 30 (15%) 76 (19%)
22
10-<15 41 (12%) 40 (11%) 81 (11%) 20 (13%) 18 (11%) 38 (12%) 21 (11%) 22 (11%) 43 (11%)
15-<20 58 (17%) 52 (15%) 110 (16%) 32 (21%) 28 (18%) 60 (19%) 26 (13%) 24 (12%) 50 (13%)
20-<25 45 (13%) 49 (14%) 94 (13%) 18 (12%) 22 (14%) 40 (13%) 27 (14%) 27 (14%) 54 (14%)
25-<30 49 (14%) 46 (13%) 95 (13%) 25 (16%) 19 (12%) 44 (14%) 24 (12%) 27 (14%) 51 (13%)
30-<40 42 (12%) 72 (20%) 114 (16%) 18 (12%) 23 (15%) 41 (13%) 24 (12%) 49 (25%) 73 (18%)
>=40 35 (10%) 30 ( 8%) 65 ( 9%) 7 ( 5%) 9 ( 6%) 16 ( 5%) 28 (14%) 21 (11%) 49 (12%)
CD4 (cells/mm3)**
n 350 357 707 154 157 311 196 200 396
mean (SD) 498 (408) 546 (401) 522 (405) 476 (370) 499 (379) 487 (374) 514 (436) 582 (414) 549 (426)
median 444 487 459 453 435 436 439 554 482
[IQR] [197, 653] [254, 751] [228, 707] [210, 623] [225, 707] [211, 663] [193, 716] [285, 790] [243, 752]
[range] [ 4-2446] [ 2-2494] [ 2-2494] [ 7-2298] [ 7-1734] [ 7-2298] [ 4-2446] [ 2-2494] [ 2-2494]
<50 40 (11%) 38 (11%) 78 (11%) 20 (13%) 19 (12%) 39 (13%) 20 (10%) 19 (10%) 39 (10%)
50-<100 21 ( 6%) 10 ( 3%) 31 ( 4%) 10 ( 6%) 6 ( 4%) 16 ( 5%) 11 ( 6%) 4 ( 2%) 15 ( 4%)
100-<200 27 ( 8%) 22 ( 6%) 49 ( 7%) 7 ( 5%) 13 ( 8%) 20 ( 6%) 20 (10%) 9 ( 5%) 29 ( 7%)
200-<350 47 (13%) 55 (15%) 102 (14%) 21 (14%) 24 (15%) 45 (14%) 26 (13%) 31 (16%) 57 (14%)
350-<500 71 (20%) 59 (17%) 130 (18%) 27 (18%) 32 (20%) 59 (19%) 44 (22%) 27 (14%) 71 (18%)
500-<1000 104 (30%) 124 (35%) 228 (32%) 55 (36%) 43 (27%) 98 (32%) 49 (25%) 81 (41%) 130 (33%)
1000-1500 32 ( 9%) 42 (12%) 74 (10%) 12 ( 8%) 18 (11%) 30 (10%) 20 (10%) 24 (12%) 44 (11%)
>=1500 8 ( 2%) 7 ( 2%) 15 ( 2%) 2 ( 1%) 2 ( 1%) 4 ( 1%) 6 ( 3%) 5 ( 3%) 11 ( 3%)
CD4/CD8 ratio**
n 346 352 698 150 153 303 196 199 395
mean (SD) 0.5 (0.9) 0.6 (0.7) 0.5 (0.8) 0.6 (1.2) 0.5 (0.4) 0.5 (0.9) 0.5 (0.4) 0.6 (0.9) 0.6 (0.7)
median 0.4 0.5 0.4 0.4 0.4 0.4 0.4 0.5 0.4
[IQR] [0.2, 0.7] [0.2, 0.8] [0.2, 0.7] [0.2, 0.6] [0.2, 0.7] [0.2, 0.7] [0.2, 0.7] [0.3, 0.8] [0.2, 0.8]
[range] [0.0-14.4] [0.0-11.1] [0.0-14.4] [0.0-14.4] [0.0-2.6] [0.0-14.4] [0.0-1.8] [0.0-11.1] [0.0-11.1]
>=1 32 ( 9%) 43 (12%) 75 (11%) 11 ( 7%) 13 ( 8%) 24 ( 8%) 21 (11%) 30 (15%) 51 (13%)
<1 314 (91%) 309 (88%) 623 (89%) 139 (93%) 140 (92%) 279 (92%) 175 (89%) 169 (85%) 344 (87%)
missing 4 5 9 4 4 8 0 1 1
Log10 Viral load
(copies/mL)**
n 350 356 706 154 156 310 196 200 396
mean (SD) 4.5 (0.8) 4.3 (0.9) 4.4 (0.8) 4.5 (1.0) 4.4 (1.0) 4.5 (1.0) 4.4 (0.7) 4.3 (0.7) 4.3 (0.7)
median 4.5 4.4 4.4 4.6 4.6 4.6 4.4 4.2 4.3
[IQR] [3.9, 5.1] [3.7, 4.9] [3.9, 5.0] [4.0, 5.2] [3.8, 5.1] [3.9, 5.1] [3.9, 5.0] [3.7, 4.7] [3.8, 4.8]
[range] [1.3-6.6] [1.3-6.5] [1.3-6.6] [1.3-6.6] [1.3-6.5] [1.3-6.6] [2.7-6.2] [2.9-6.1] [2.7-6.2]
Viral load
(copies/mL)**
<400 5 ( 1%) 10 ( 3%) 15 ( 2%) 5 ( 3%) 10 ( 6%) 15 ( 5%) 0 ( 0%) 0 ( 0%) 0 ( 0%)
400-<1,000 11 ( 3%) 6 ( 2%) 17 ( 2%) 7 ( 5%) 4 ( 3%) 11 ( 4%) 4 ( 2%) 2 ( 1%) 6 ( 2%)
23
1,000-<10,000 77 (22%) 107 (30%) 184 (26%) 28 (18%) 34 (22%) 62 (20%) 49 (25%) 73 (37%) 122 (31%)
10,000-<50,000 115 (33%) 113 (32%) 228 (32%) 41 (27%) 36 (23%) 77 (25%) 74 (38%) 77 (39%) 151 (38%)
50,000-<100,000 44 (13%) 45 (13%) 89 (13%) 23 (15%) 21 (13%) 44 (14%) 21 (11%) 24 (12%) 45 (11%)
100,000-<500,000 82 (23%) 61 (17%) 143 (20%) 40 (26%) 42 (27%) 82 (26%) 42 (21%) 19 (10%) 61 (15%)
500,000- 10 ( 3%) 10 ( 3%) 20 ( 3%) 6 ( 4%) 6 ( 4%) 12 ( 4%) 4 ( 2%) 4 ( 2%) 8 ( 2%)
<1,000,000
>=1,000,000 6 ( 2%) 4 ( 1%) 10 ( 1%) 4 ( 3%) 3 ( 2%) 7 ( 2%) 2 ( 1%) 1 ( 1%) 3 ( 1%)
missing 0 1 1 0 1 1 0 0 0
History of WHO
staging
stage1 124 (35%) 146 (41%) 270 (38%) 60 (39%) 68 (43%) 128 (41%) 64 (33%) 78 (39%) 142 (36%)
stage2 129 (37%) 119 (33%) 248 (35%) 56 (36%) 57 (36%) 113 (36%) 73 (37%) 62 (31%) 135 (34%)
stage3 69 (20%) 60 (17%) 129 (18%) 25 (16%) 22 (14%) 47 (15%) 44 (22%) 38 (19%) 82 (21%)
stage4 28 ( 8%) 32 ( 9%) 60 ( 8%) 13 ( 8%) 10 ( 6%) 23 ( 7%) 15 ( 8%) 22 (11%) 37 ( 9%)
Total cholesterol
(mg/dL)
n 337 347 684 148 151 299 189 196 385
mean (SD) 139 ( 29) 137 ( 31) 138 ( 30) 137 ( 29) 132 ( 31) 134 ( 30) 141 ( 28) 141 ( 30) 141 ( 29)
median 135 135 135 135 128 131 137 139 138
[IQR] [118, 155] [116, 155] [117, 155] [116, 153] [112, 150] [115, 151] [122, 158] [120, 162] [121, 160]
[range] [ 61-256] [ 32-239] [ 32-256] [ 70-256] [ 32-239] [ 32-256] [ 61-236] [ 81-228] [ 61-236]
Triglycerides
(mg/dL)
n 343 349 692 148 151 299 195 198 393
mean (SD) 95 ( 46) 96 ( 46) 96 ( 46) 98 ( 48) 95 ( 47) 96 ( 47) 94 ( 44) 97 ( 46) 95 ( 45)
median 86 89 89 89 89 89 84 89 87
[IQR] [ 62, 116] [ 63, 115] [ 62, 115] [ 62, 121] [ 62, 111] [ 62, 115] [ 62, 112] [ 64, 119] [ 64, 115]
[range] [ 1-374] [ 20-372] [ 1-374] [ 27-259] [ 20-372] [ 20-372] [ 1-374] [ 24-300] [ 1-374]
HDL cholesterol
(mg/dL)
n 333 346 679 148 151 299 185 195 380
mean (SD) 44 ( 16) 43 ( 16) 43 ( 16) 40 ( 16) 38 ( 16) 39 ( 16) 47 ( 16) 46 ( 15) 46 ( 15)
median 43 40 41 37 35 35 46 43 45
[IQR] [ 31, 53] [ 32, 50] [ 31, 51] [ 28, 50] [ 29, 43] [ 29, 46] [ 37, 56] [ 36, 55] [ 36, 55]
[range] [ 5-101] [ 5- 94] [ 5-101] [ 12-101] [ 5- 94] [ 5-101] [ 5- 99] [ 15- 92] [ 5- 99]
LDL cholesterol
(mg/dL)
n 343 349 692 148 151 299 195 198 393
mean (SD) 81 ( 30) 80 ( 30) 80 ( 30) 79 ( 29) 79 ( 29) 79 ( 29) 82 ( 32) 81 ( 30) 82 ( 31)
median 77 77 77 77 77 77 77 79 77
24
[IQR] [ 62, 98] [ 61, 96] [ 62, 97] [ 61, 97] [ 61, 98] [ 61, 97] [ 62, 99] [ 61, 96] [ 62, 97]
[range] [ 12-217] [ 3-208] [ 3-217] [ 12-168] [ 3-208] [ 3-208] [ 26-217] [ 14-205] [ 14-217]
*WHO Child Growth Charts and WHO Reference 2007 Charts, version WHO. BMI-for-age calculated for <19y/o, metrics are considered missing if BMI-for-age <-5/>5.
+Other modes of infections: one participant injecting drug use, one participant possible transmission father to child (Father HIV+, Mother HIV-, no history of sexual intercourse).
**Mean of measurement at screening and randomisation if both are available
Table S6.2 Baseline characteristics: Antiretroviral exposure [ODYSSEY B only]

B
DTG SOC Total
Participants randomised 196 200 396
Number of different drugs ever received excluding PMTCT, median [range]
n 196 200 396
All classes 3.0 [3.0-8.0] 3.0 [3.0-7.0] 3.0 [3.0-8.0]
NRTI 2.0 [2.0-6.0] 2.0 [2.0-5.0] 2.0 [2.0-6.0]
NNRTI 1.0 [0.0-2.0] 1.0 [0.0-2.0] 1.0 [0.0-2.0]
PI 0.0 [0.0-1.0] 0.0 [0.0-1.0] 0.0 [0.0-1.0]
ART Class Exposure
NRTI/NNRTI 190 (97%) 192 (96%) 382 (96%)
NRTI/NNRTI/PIs 1 ( 1%) 3 ( 2%) 4 ( 1%)
NRTI/PIs 5 ( 3%) 5 ( 3%) 10 ( 3%)
missing 0 0 0
Cumulative ART exposure (years), median [range]
n 196 200 396
All classes 5.3 [0.8-13.6] 5.6 [0.7-15.4] 5.5 [0.7-15.4]
NRTI 5.3 [0.8-13.6] 5.6 [0.7-15.4] 5.5 [0.7-15.4]
NNRTI 5.0 [0.0-13.6] 5.2 [0.0-15.4] 5.2 [0.0-15.4]
PI 0.0 [0.0-11.2] 0.0 [0.0-11.1] 0.0 [0.0-11.2]
ART Regimen Class Prior to Randomisation
Monotherapy* 0 ( 0%) 1 ( 1%) 1 ( 0%)
NRTI/NNRTI 191 (97%) 192 (96%) 383 (97%)
NRTI/PIs 5 ( 3%) 7 ( 4%) 12 ( 3%)
missing 0 0 0
pant
25
S 7 Efficacy
Table S7.1 Comparison of proportion with clinical or virological failure by 48 weeks
Total A B
DTG SOC DTG vs. SOC DTG SOC DTG vs. SOC DTG SOC DTG vs. SOC
Participants randomised 350 357 154 157 196 200
Total participants meeting primary endpoint 20 (5.7%) 42 (11.8%) 9 (5.8%) 20 (12.7%) 11 (5.6%) 22 (11.0%)
Insufficient virological response 0 (0.0%) 3 (0.8%) 0 (0.0%) 2 (1.3%) 0 (0.0%) 1 (0.5%)
Confirmed VL>=400 copies/mL 13 (3.7%) 31 (8.7%) 4 (2.6%) 12 (7.6%) 9 (4.6%) 19 (9.5%)
Severe WHO 3 0 (0.0%) 1 (0.3%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (0.5%)
WHO 4^ 7 (2.0%) 5 (1.4%) 5 (3.2%) 5 (3.2%) 2 (1.0%) 0 (0.0%)
Death 0 (0.0%) 2 (0.6%) 0 (0.0%) 1 (0.6%) 0 (0.0%) 1 (0.5%)
Unadjusted* estimated probability of failure 0.058 0.120 0.060 0.131 0.058 0.111
[95%CI] [0.038, 0.085] [0.087, 0.151] [0.021, 0.100] [0.088, 0.192] [0.026, 0.093] [0.071, 0.160]
Difference (DTG-SOC) -0.062 -0.072 -0.053
[95%CI] [-0.102, -0.019] [-0.140, -0.012] [-0.108, -0.001]
Adjusted** estimated probability of failure 0.059 0.120 0.060 0.131 0.058 0.111
[95%CI] [0.038, 0.089] [0.088, 0.154] [0.027, 0.101] [0.082, 0.188] [0.032, 0.097] [0.074, 0.156]
[95%CI] [-0.102, -0.021] [-0.135, -0.007] [-0.106, -0.004]
^WHO 4 events include 2 deaths at diagnosis (1 DTG, 1 SOC)
*Adjusted for ODSSEY A and B strata only in total, unadjusted in A and B.
**Adjusted all for stratification factors. Analysis conducted using same approach as primary analysis of primary endpoint at 96 weeks (see S3.2 statistical methods)
Table S7.2 Incidence of clinical or virological failure by 48 weeks

Total A B
DTG SOC DTG vs SOC DTG SOC DTG vs SOC DTG SOC DTG vs SOC
Person years 315 316 137 136 178 181
Event rate (per 100 person years) 6.3 13.3 6.6 14.7 6.2 12.2
(95% CI) (4.1, 9.8) (9.8, 18.0) (3.4, 12.6) (9.5, 22.8) (3.4, 11.2) (8.0, 18.5)
Adj. hazard ratio* 0.47 0.44 0.50
(95% CI) (0.28, 0.80) (0.20, 0.96) (0.24, 1.03)
*Adjusted for all stratification factors. Hazard ratios from Cox regression models presented as an alternative analysis to the comparison of proportion with clinical or virological failure (see
table above)
26
Table S7.3 Primary analysis of primary endpoint: Comparison of proportion with clinical or virological failure by 96
weeks
Total A B
Severe WHO 3 0 (0.0%) 1 (0.3%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (0.5%)
WHO 4^ 7 (2.0%) 5 (1.4%) 5 (3.2%) 5 (3.2%) 2 (1.0%) 0 (0.0%)
Death 0 (0.0%) 2 (0.6%) 0 (0.0%) 1 (0.6%) 0 (0.0%) 1 (0.5%)
[95%CI] [0.099, 0.174] [0.173, 0.259] [0.053, 0.151] [0.163, 0.297] [0.109, 0.213] [0.157, 0.271]
[95%CI] [-0.136, -0.022] [-0.207, -0.043] [-0.112, 0.038]
[95%CI] [0.103, 0.174] [0.178, 0.263] [0.054, 0.146] [0.156, 0.296] [0.122, 0.223] [0.152, 0.265]
[95%CI] [-0.142, -0.031] [-0.206, -0.041] [-0.118, 0.028]
P-value*** 0.004 0.003 0.220
A/B x arm interaction, P-value+ 0.157
*Adjusted for ODSSEY A and B strata only in total, unadjusted in A and B
**Adjusted all for stratification factors (primary analysis)
***Bootstrap p-value
+Z-test
Table S7.4 Incidence of clinical or virological failure by 96 weeks (alternative approach to analysis of primary endpoint)
Total A B
Person years 602 581 266 247 337 334
(95% CI) (5.9, 10.4) (10.3, 16.2) (3.4, 9.4) (9.8, 19.2) (6.7, 13.4) (9.0, 16.7)
(95% CI) (0.42, 0.86) (0.22, 0.75) (0.48, 1.21)
*Adjusted for all stratification factors. Hazard ratios from Cox regression models presented as an alternative analysis to the primary analysis (see table above)
27
Table S7.5 Comparison of proportion with clinical or virological failure by 144 weeks
Total A B
Severe WHO 3 0 (0.0%) 1 (0.3%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (0.5%)
WHO 4^ 8 (2.3%) 5 (1.4%) 6 (3.9%) 5 (3.2%) 2 (1.0%) 0 (0.0%)
Death 0 (0.0%) 2 (0.6%) 0 (0.0%) 1 (0.6%) 0 (0.0%) 1 (0.5%)
[95%CI] [0.131, 0.215] [0.217, 0.312] [0.081, 0.184] [0.179, 0.324] [0.148, 0.267] [0.218, 0.353]
[95%CI] [-0.150, -0.028] [-0.203, -0.031] [-0.154, 0.018]
[95%CI] [0.132, 0.213] [0.219, 0.317] [0.077, 0.185] [0.178, 0.323] [0.157, 0.274] [0.217, 0.354]
[95%CI] [-0.161, -0.040] [-0.208, -0.032] [-0.155, 0.012]
*Adjusted for ODSSEY A and B strata only in total, unadjusted in A and B
**Adjusted all for stratification factors. Analysis conducted using same approach as primary analysis of the primary endpoint at 96 weeks (see S3.2 statistical methods)
Table S7.6 Incidence of clinical or virological failure by 144 weeks

Total A B
Person years 818 774 364 331 454 443
(95% CI) (5.3, 8.9) (9.1, 13.9) (3.3, 8.2) (7.8, 15.1) (5.9, 11.2) (8.8, 15.2)
(95% CI) (0.43, 0.85) (0.28, 0.85) (0.46, 1.07)
*Adjusted for all stratification factors. Hazard ratios from Cox regression models presented as an alternative analysis to the comparison of proportion with clinical or virological failure (see
table above).
28
Figure S7.1 Kaplan Meier: Time from randomisation to clinical or virological failure by 144 weeks
29
Table S7.7 Comparison of proportion of participants with HIV-1 RNA <50c/ml at 48 weeks
Total A B
DTG SOC DTG SOC DTG SOC
HIV-1 RNA <50c/mL at 48 weeks 262 249 113 113 149 136
HIV-1 RNA >=50c/mL at 48 weeks 80 89 37 34 43 55
Unadjusted Proportion<50c/mL 76.6 73.7 75.3 76.9 77.6 71.2
[95%Confidence Interval] [71.8, 80.8] [68.7, 78.1] [67.7, 81.6] [69.3, 83.0] [71.1, 83.0] [64.3, 77.2]
Estimated Difference (DTG-SOC)+ 2.9 -1.5 6.4
[95% Confidence Interval] [-3.6, 9.4] [-11.2, 8.2] [-2.3, 15.1]
+Difference in proportion (95% CI) in total population estimated by Mantel-Haenszel weighted mean of proportions in ODYSSEY A and B.
Total A B
Estimated Difference (DTG-SOC)+ 4.5 5.1 4.1
Total A B
[95% Confidence Interval] [-1.6, 10.9] [-9.8, 8.6] [0.1, 17.0]
30
Total A B
Table S7.11 FDA snapshot algorithm - comparison of proportion of participants with HIV-1 RNA <50 c/ml and >=50 c/ml at
48 weeks
Total A B
HIV-RNA<50 c/ml (Total participants) 257 235 111 105 146 130
Proportion 73.4% 65.8% 72.1% 66.9% 74.5% 65.0%
Treatment difference (DTG-SOC)+ 7.6 5.2 9.5
[95% Confidence Interval] [0.8, 14.4] [-5.0, 15.4] [0.5, 18.5]
HIV-RNA>=50 c/ml (Total participants) 79 93 37 37 42 56
Proportion 22.6% 26.1% 24.0% 23.6% 21.4% 28.0%
Treatment difference (DTG-SOC)+ -3.5 0.5 -6.6
Components of HIV-RNA>=50 c/ml
HIV-RNA >=50 c/ml - in window 75 80 35 29 40 51
Non-permitted ART (other than toxicity) 3 6 2 5 1 1
VL>=50 c/ml prior to permitted switch or LTFU 1 7 0 3 1 4
Missing VL in week 48 window (Total participants) 14 29 6 15 8 14
Proportion 4.0% 8.1% 3.9% 9.6% 4.1% 7.0%
VL<50 c/ml prior to permitted switch or LTFU 4 11 0 9 4 2
Non-permitted ART due to toxicity or died 5 7 4 2 1 5
Initial regimen but no VL in window 5 11 2 4 3 7
31
Table S7.12 FDA snapshot algorithm - comparison of proportion of participants with HIV-1 RNA <400 c/ml and >=400 c/ml
at 48 weeks
Total A B
Proportion 85.1% 75.9% 85.1% 72.6% 85.2% 78.5%
[95% Confidence Interval] [3.4, 15.0] [3.5, 21.4] [-0.9, 14.3]
Proportion 11.7% 15.4% 12.3% 16.6% 11.2% 14.5%
Treatment difference (DTG-SOC)+ -3.7 -4.2 -3.3
Proportion 3.1% 8.7% 2.6% 10.8% 3.6% 7.0%
Table S7.13 FDA snapshot algorithm - comparison of proportion of participants with HIV-1 RNA <50 c/ml and >=50 c/ml at
96 weeks
Total A B
Proportion 74.6% 65.3% 74.7% 64.3% 74.5% 66.0%
Proportion 19.4% 26.1% 18.2% 22.9% 20.4% 28.5%
32
[95% Confidence Interval] [-12.8, -0.5] [-13.7, 4.2] [-16.5, 0.3]

Proportion 6.0% 8.7% 7.1% 12.7% 5.1% 5.5%
Table S7.14 FDA snapshot algorithm - comparison of proportion of participants with HIV-1 RNA <400 c/ml and >=400 c/ml
at 96 weeks
Total A B
Proportion 82.3% 73.7% 81.8% 70.1% 82.7% 76.5%
Proportion 12.3% 16.0% 11.0% 15.3% 13.3% 16.5%
Proportion 5.4% 10.4% 7.1% 14.6% 4.1% 7.0%
33
Figure S7.2 Per-protocol analysis
Figure legend: 30 participants (5 meeting primary endpoint) were excluded in per-protocol analysis (23 randomised
within incorrect strata; 4 did not switch 2 drugs at enrolment; 3 did not meet baseline VL requirements). In addition,
33 were censored prior to meeting the primary endpoint due to a change of third agent for toxicity, protocol deviation,
pregnancy or ART discontinuation for >31days
34
Figure S7.3 Secondary analysis: excluding participants in SOC arm
initiating integrase inhibitor
Figure legend: 1 SOC participant was excluded due to initiating an integrase inhibitor (EVG) at enrolment.
35
Figure S7.4 Secondary analysis: per-protocol and excluding participants in
SOC arm initiating integrase inhibitor
Figure legend: 30 participants (5 meeting primary endpoint) were excluded in per-protocol analysis (23 randomised
within incorrect strata (1 SOC participant initiating INSTI, therefore same analysis as per-protocol); 4 did not switch 2
drugs at enrolment; 3 did not meet baseline VL requirements). In addition, 33 were censored prior to meeting the
primary endpoint due to a change of third agent for toxicity, protocol deviation, pregnancy or ART discontinuation for
>31days
36
Figure S7.5 Sensitivity analysis: censoring at time of ART switch for

treatment failure before confirmatory viral load
Figure legend: 1 participant was censored at week 60 prior to meeting primary endpoint due to switching ART for
treatment failure before confirmatory viral load.
37
Figure S7.6 Sensitivity analysis: date of failure at confirmed VL>=400c/ml
Figure legend: Using the actual date of confirmatory viral load>=400c/ml, rather than the date of the next scheduled
visit, 1 additional participant met the primary endpoint in the sensitivity analysis (censored in primary analysis due to
meeting endpoint in primary analysis after last VL, given the use of next scheduled VL). In addition, 49 with virological
failure had a different date of failure compared to in the primary analysis.
38
Figure S7.7 Sensitivity analysis: date of failure at first VL>=400c/ml
Figure legend: Using the date of first of two viral loads>=400c/ml, 5 additional participants met the primary endpoint in
the sensitivity analysis (censored in primary analysis due to meeting endpoint in primary analysis after week 96). In
addition, 106 with virological failure had a different date of failure compared to in the primary analysis.
39
Figure S7.8 Analysis of the primary endpoint adjusted for baseline viral
load or baseline CD4
Figure legend: This analysis was data driven and was done because of a slight baseline imbalance in
favour of SOC in baseline viral load and CD4
40
Table S7.15 Total population - Subgroup analyses for primary endpoint

DTG SOC
Participants Total participants meeting Participants Total participants meeting Adjusted hazard ratio
randomised primary endpoint randomised primary endpoint (95% CI)
ODYSSEY
A/ODYSSEY B*
A 154 15 (9.7%) 157 34 (21.7%) 0.40 (0.22, 0.74)
B 196 32 (16.3%) 200 41 (20.5%) 0.77 (0.48, 1.22)
Sex
male 176 26 (14.8%) 186 37 (19.9%) 0.71 (0.43, 1.17)
female 174 21 (12.1%) 171 38 (22.2%) 0.50 (0.29, 0.85)
Age at baseline
<12years 168 18 (10.7%) 175 36 (20.6%) 0.47 (0.27, 0.83)
>=12years 182 29 (15.9%) 182 39 (21.4%) 0.72 (0.44, 1.16)
Weight at baseline
14-<25kg 110 12 (10.9%) 107 21 (19.6%) 0.49 (0.24, 1.01)
25-<35kg 96 16 (16.7%) 110 26 (23.6%) 0.68 (0.36, 1.27)
>=35kg 144 19 (13.2%) 140 28 (20.0%) 0.63 (0.35, 1.13)
CD4% at baseline
<10% 80 19 (23.8%) 68 16 (23.5%) 0.93 (0.47, 1.81)
10-25% 144 17 (11.8%) 141 36 (25.5%) 0.41 (0.23, 0.74)
>25% 126 11 (8.7%) 148 23 (15.5%) 0.55 (0.27, 1.13)
Baseline viral load
<10,000 93 14 (15.1%) 123 25 (20.3%) 0.76 (0.39, 1.47)
10,000-<100,000 159 18 (11.3%) 158 28 (17.7%) 0.59 (0.33, 1.07)
>=100,000 98 15 (15.3%) 75 22 (29.3%) 0.42 (0.21, 0.81)
Resistance testing
strata
no 309 45 (14.6%) 314 68 (21.7%) 0.64 (0.44, 0.93)
yes 41 2 (4.9%) 43 7 (16.3%) 0.25 (0.05, 1.19)
NRTI backbone
strata
ABC/3TC 232 26 (11.2%) 235 52 (22.1%) 0.47 (0.29, 0.75)
All other 118 21 (17.8%) 122 23 (18.9%) 0.91 (0.50, 1.64)
*ODYSSEY A/B subgroup analysis performed using joint model, unlike the primary analysis, where A/B effects are estimated in separate models.
41
Table S7.16 ODYSSEY A - Subgroup analyses for primary endpoint

DTG SOC
Sex
male 67 9 (13.4%) 80 17 (21.3%) 0.62 (0.28, 1.39)
female 87 6 (6.9%) 77 17 (22.1%) 0.27 (0.11, 0.68)
Age at baseline
<12years 79 9 (11.4%) 89 23 (25.8%) 0.38 (0.18, 0.83)
>=12years 75 6 (8.0%) 68 11 (16.2%) 0.47 (0.17, 1.28)
Weight at baseline
14-<25kg 51 7 (13.7%) 49 14 (28.6%) 0.42 (0.17, 1.04)
25-<35kg 42 4 (9.5%) 49 12 (24.5%) 0.35 (0.11, 1.08)
>=35kg 61 4 (6.6%) 59 8 (13.6%) 0.47 (0.14, 1.57)
CD4% at baseline
<10% 34 8 (23.5%) 38 9 (23.7%) 0.90 (0.35, 2.35)
10-25% 70 4 (5.7%) 68 14 (20.6%) 0.24 (0.08, 0.74)
>25% 50 3 (6.0%) 51 11 (21.6%) 0.26 (0.07, 0.95)
Baseline viral load
<10,000 40 2 (5.0%) 48 10 (20.8%) 0.24 (0.05, 1.11)
10,000-<100,000 64 7 (10.9%) 57 7 (12.3%) 0.85 (0.30, 2.43)
>=100,000 50 6 (12.0%) 51 17 (33.3%) 0.27 (0.11, 0.69)
Resistance testing
strata
no 121 14 (11.6%) 124 30 (24.2%) 0.44 (0.23, 0.83)
yes 33 1 (3.0%) 33 4 (12.1%) 0.21 (0.02, 1.87)
NRTI backbone
strata
ABC/3TC 126 13 (10.3%) 127 30 (23.6%) 0.40 (0.21, 0.77)
All other 28 2 (7.1%) 30 4 (13.3%) 0.48 (0.09, 2.62)
42
Table S7.17 ODYSSEY B - Subgroup analyses for primary endpoint

DTG SOC
Sex
male 109 17 (15.6%) 106 20 (18.9%) 0.79 (0.41, 1.50)
female 87 15 (17.2%) 94 21 (22.3%) 0.74 (0.38, 1.45)
Age at baseline
<12years 89 9 (10.1%) 86 13 (15.1%) 0.64 (0.27, 1.51)
>=12years 107 23 (21.5%) 114 28 (24.6%) 0.84 (0.48, 1.46)
Weight at baseline
14-<25kg 59 5 (8.5%) 58 7 (12.1%) 0.67 (0.21, 2.11)
25-<35kg 54 12 (22.2%) 61 14 (23.0%) 0.98 (0.45, 2.14)
>=35kg 83 15 (18.1%) 81 20 (24.7%) 0.68 (0.35, 1.33)
CD4% at baseline
<10% 46 11 (23.9%) 30 7 (23.3%) 0.98 (0.38, 2.54)
10-25% 74 13 (17.6%) 73 22 (30.1%) 0.53 (0.27, 1.06)
>25% 76 8 (10.5%) 97 12 (12.4%) 0.84 (0.34, 2.07)
Baseline viral load
<10,000 53 12 (22.6%) 75 15 (20.0%) 1.18 (0.55, 2.53)
10,000-<100,000 95 11 (11.6%) 101 21 (20.8%) 0.49 (0.24, 1.03)
>=100,000 48 9 (18.8%) 24 5 (20.8%) 0.86 (0.29, 2.56)
Resistance testing
strata
no 188 31 (16.5%) 190 38 (20.0%) 0.80 (0.50, 1.28)
yes 8 1 (12.5%) 10 3 (30.0%) 0.30 (0.03, 2.98)
NRTI backbone
strata
ABC/3TC 106 13 (12.3%) 108 22 (20.4%) 0.56 (0.28, 1.11)
All other 90 19 (21.1%) 92 19 (20.7%) 1.00 (0.53, 1.89)
43
Figure S7.9 Subgroup analysis: Treatment effects stratified by calendar time of DTG dose increases
Figure legend: Treatment effects stratified by calendar time of dose increase, when children 25-<40kg were recommended to increase DTG dose to 50mg FCT QD (25/07/2018), and when
children 14-<20kg were recommended to change to DTG 25mg QD dispersible tablets (07/06/2019).
44
Table S7.18 Rate of clinical events to trial censoring date: WHO 4, severe WHO 3 and death
Total A B
Participants randomised and included 350 357 707 154 157 311 196 200 396
Person years 943 933 1875 418 408 826 524 525 1049
Total number of events [Number of participants]# 10 [8] 8 [8] 18 [16] 8 [6] 6 [6] 14 [12] 2 [2] 2 [2] 4 [4]
Severe WHO 3 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1]
WHO 4 10 [8] 5 [5] 15 [13] 8 [6] 5 [5] 13 [11] 2 [2] 0 [0] 2 [2]
Death 2 [2] 3 [3] 5 [5] 2 [2] 2 [2] 4 [4] 0 [0] 1 [1] 1 [1]
Number of events [Number of children]
Infectious Disease 8 [6] 5 [5] 13 [11] 7 [5] 4 [4] 11 [9] 1 [1] 1 [1] 2 [2]
Bronchiectasis - infectious exacerbation 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1]
Cryptococcal meningitis 2 [1] 0 [0] 2 [1] 2 [1] 0 [0] 2 [1] 0 [0] 0 [0] 0 [0]
Pneumonia - other bacterial+Presumed septicaemia/bacteremia - not 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
investigated *
Pneumonia no organism identified+Candidiasis of oesophagus, trachea, 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
bronchi or lungs
Presumed septicaemia/bacteremia - no organism+Tuberculosis - 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
disseminated
Tuberculosis - disseminated 5 [4] 1 [1] 6 [5] 4 [3] 1 [1] 5 [4] 1 [1] 0 [0] 1 [1]
Tuberculosis - disseminated * 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Renal 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Renal failure - chronic * 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Systemic 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Wasting syndrome uninvestigated+Oral candida+Chronic diarrhoea not 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
investigated
Tumours 1 [1] 1 [1] 2 [2] 0 [0] 1 [1] 1 [1] 1 [1] 0 [0] 1 [1]
Kaposi's sarcoma cutaneous 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
Non Hodgkin lymphoma * 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Other 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1]
Death, cause unknown 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1]
Event rate (all events)
Event rate (per 100 person years) 1.1 0.9 1.0 1.9 1.5 1.7 0.4 0.4 0.4
(95% CI) (0.6, 2.0) (0.4, (0.6, (1.0, 3.8) (0.7, (1.0, (0.1, 1.5) (0.1, (0.1,
1.7) 1.5) 3.3) 2.9) 1.5) 1.0)
Rate ratio+ 1.23 1 (ref) 1.30 1 (ref) 1.00 1 (ref)
(95% CI) (0.45, - (0.41, - (0.14,
3.33) 4.13) 7.09)
Adj. Rate ratio++ 1.23 1 (ref) 1.31 1 (ref) 1.00 1 (ref)
(95% CI) (0.45, - (0.41, - (0.14,
3.34) 4.15) 7.04)
Time to first event (WHO 4, severe WHO 3 or death)
Hazard ratio+ 1.00 1 (ref) 1.00 1 (ref) 1.01 1 (ref)
45
(95% CI) (0.38, - (0.32, - (0.14,

2.67) 3.10) 7.19)
Adj. hazard ratio++ 1.00 1 (ref) 1.01 1 (ref) 1.00 1 (ref)
(95% CI) (0.38, - (0.32, - (0.14,
2.68) 3.12) 7.13)
Time to first event (WHO 4 or severe WHO 3)
(95% CI) (0.46, - (0.37, - (0.18,
3.85) 3.93) 22.28)
(95% CI) (0.46, - (0.37, - (0.18,
3.86) 3.96) 22.11)
*Resulted in death
+Adjusted for ODYSSEY A and B strata in total. Unadjusted in A and B comparison
++Adjusted for all stratification factors
# Events can meet the WHO stage criteria and result in death, therefore the sum of WHO stage events and deaths do not sum to the total number of events
Table S7.19 Rate of clinical events to week 96: WHO 4, severe WHO 3 and death
Total A B
Person years 635 634 1269 279 273 552 357 361 718
Total number of events [Number of participants] # 9 [7] 8 [8] 17 [15] 7 [5] 6 [6] 13 [11] 2 [2] 2 [2] 4 [4]
Severe WHO 3 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1]
WHO 4 9 [7] 5 [5] 14 [12] 7 [5] 5 [5] 12 [10] 2 [2] 0 [0] 2 [2]
Death 1 [1] 3 [3] 4 [4] 1 [1] 2 [2] 3 [3] 0 [0] 1 [1] 1 [1]
Number of events [Number of children]
Pneumonia - other bacterial+Presumed septicaemia/bacteremia - not 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
investigated *
Pneumonia no organism identified+Candidiasis of oesophagus, trachea, 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
bronchi or lungs
Presumed septicaemia/bacteremia - no organism+Tuberculosis - 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
disseminated
Systemic 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Wasting syndrome uninvestigated+Oral candida+Chronic diarrhoea not 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
46
investigated
Tumours 1 [1] 1 [1] 2 [2] 0 [0] 1 [1] 1 [1] 1 [1] 0 [0] 1 [1]
Other 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1]
(95% CI) (0.7, 2.7) (0.6, (0.8, (1.2, 5.3) (1.0, (1.4, (0.1, 2.2) (0.1, (0.2,
2.5) 2.2) 4.9) 4.1) 2.2) 1.5)
Rate ratio+ 1.11 1 (ref) 1.14 1 (ref) 1.01 1 (ref)
(95% CI) (0.39, - (0.34, - (0.14,
3.14) 3.85) 7.15)
Adj. Rate ratio++ 1.12 1 (ref) 1.15 1 (ref) 1.00 1 (ref)
(95% CI) (0.40, - (0.34, - (0.14,
3.14) 3.87) 7.08)
Time to first event (WHO 4, severe WHO 3 or death)
(95% CI) (0.32, - (0.26, - (0.14,
2.42) 2.74) 7.19)
(95% CI) (0.32, - (0.26, - (0.14,
2.43) 2.76) 7.13)
Time to first event (WHO 4 or severe WHO 3)
(95% CI) (0.39, - (0.29, - (0.18,
3.48) 3.46) 22.28)
(95% CI) (0.39, - (0.29, - (0.18,
3.50) 3.49) 22.11)
*Resulted in death
+Adjusted for ODYSSEY A and B strata in total. Unadjusted in A and B comparison
++Adjusted for all stratification factors
# Events can meet the WHO stage criteria and result in death, therefore the sum of WHO stage events and deaths do not sum to the total number of events
47
Table S7.20 Details of WHO 3 (Severe) or 4 events or deaths during follow-up (until trial censoring date)
ID A/B Treatment ART regimen at Grade Age Event Event Type
arm event Week
1 A DTG ABC 3TC DTG 3 14 4 Tuberculosis - disseminated WHO4
2 A DTG ABC 3TC DTG 4 6 8 Tuberculosis - disseminated Death + WHO 4
3 A DTG ABC 3TC DTG 4 12 21 Cryptococcal meningitis WHO4
3 A DTG ABC 3TC DTG 4 13 57 Cryptococcal meningitis WHO4
6 A DTG ABC 3TC DTG 4 17 146 Renal failure chronic Death + WHO 4
7 B DTG ABC 3TC DTG 3 13 5 Tuberculosis - disseminated WHO4
8 B DTG TDF 3TC DTG 2 17 44 Kaposi's sarcoma cutaneous WHO4
9 A SOC TDF 3TC EFV 4 13 30 Non Hodgkin lymphoma Death + WHO 4
10 A SOC ABC 3TC EFV 3 12 19 Pneumonia no organism identified+Candidiasis of oesophagus, WHO4
trachea, bronchi or lungs
11 A SOC ABC 3TC EFV 3 15 2 Pneumonia - other bacterial+Presumed septicaemia/bacteremia - Death
not investigated
12 A SOC ABC 3TC EFV 3 8 23 Wasting syndrome uninvestigated+Oral candida+Chronic WHO4
diarrhoea not investigated
13 A SOC ABC 3TC EFV 4 11 1 Tuberculosis - disseminated WHO4
14 A SOC ABC 3TC EFV 3 9 1 Presumed septicaemia/bacteremia - no organism+Tuberculosis - WHO4
disseminated
15 B SOC ABC 3TC LOP 4 16 32 Death, cause unknown Death
16 B SOC ABC 3TC LOP 3 13 4 Bronchiectasis - infectious exacerbation Severe WHO3
48
Table S7.21 Treatment emergent resistance mutations post-failure in
participants exposed to drug-class
Treatment emergent resistance mutations post-failure*
ODYSSEY A
DTG SOC
NRTI
Any 0 13
A62 0 3
K65 0 2
D67 0 1
K70 0 1
L74 0 4
V75 0 2
Y115 0 5
F116 0 1
M184 0 11
NNRTI
Any - 19
L100 - 3
K101 - 4
K103 - 10
V106 - 7
V108 - 4
Y181 - 2
Y188 - 1
G190 - 3
H221 - 2
P225 - 4
ODYSSEY B
DTG SOC
NRTI
Any 2 3
A62 1 0
D67 0 1
L74 0 1
M184 1 1
NNRTI
Any - 2
K101 - 1
K103 - 1
E138 - 1
G190 - 1
P225 - 1
PI
Any - 2
M46 - 1
I50 - 1
I54 - 1
V82 - 1
IN
Any** 4 -
G118 2 -
Q148 2 -
R263 1 -
* Only reported for participants for whom a resistance test has been performed at baseline and post-
failure and exposed to drug-class during trial -
exposed to drug-class). Each participant may have one or more mutation to one or more drug-class.
**4 participants with emergent INSTI resistance: 2 Q148R/K, 1 G118R, 1 G118R+R263K.
49
S 8 Immunology
Throughout this section, n refers to the number of participants with available measurement at each visit week. Numbers in models may be lower where there are missing
data at baseline.
Table S8.1 Total population - Changes in CD4 count over follow-up

Weeks since randomisation DTG SOC Unadjusted Difference* Adjusted Difference**
n mean (SE) n mean (SE) mean (SE) [95% CI] mean (SE) [95% CI]
4 346 86 ( 10) 348 67 ( 10) 18 ( 14) [-10, 47] 18 ( 14) [-10, 46]
12 341 136 ( 12) 348 111 ( 12) 25 ( 17) [ -8, 57] 25 ( 17) [ -8, 57]
24 343 163 ( 13) 344 138 ( 13) 25 ( 18) [ -9, 60] 25 ( 18) [-10, 60]
48 332 219 ( 14) 338 189 ( 14) 29 ( 19) [ -9, 67] 29 ( 19) [ -9, 67]
72 341 255 ( 16) 336 227 ( 16) 28 ( 22) [-16, 72] 29 ( 22) [-15, 73]
96 334 265 ( 17) 328 230 ( 17) 34 ( 24) [-13, 81] 35 ( 24) [-12, 82]
Average treatment differences through follow-up+ 27 ( 14) [ 0, 54] 27 ( 14) [ -0, 53]
Table S8.2 ODYSSEY A - changes in CD4 count over follow-up

4 154 117 ( 14) 151 104 ( 14) 13 ( 19) [-25 51] 13 ( 19) [-25 51]
12 151 171 ( 15) 152 161 ( 15) 9 ( 22) [-33 52] 10 ( 22) [-33 52]
24 150 189 ( 18) 150 156 ( 18) 33 ( 25) [-17 83] 33 ( 25) [-17 82]
48 145 272 ( 20) 145 213 ( 20) 60 ( 28) [ 5 114] 62 ( 28) [ 8 116]
72 148 288 ( 22) 145 244 ( 22) 44 ( 31) [-18 106] 46 ( 31) [-16 107]
96 149 311 ( 23) 139 267 ( 24) 44 ( 33) [-22 109] 44 ( 33) [-21 109]
Average treatment differences through follow-up+ 34 ( 19) [ -3, 71] 34 ( 19) [ -3, 70]
Table S8.3 ODYSSEY B - changes in CD4 count over follow-up

4 192 59 ( 14) 197 41 ( 14) 18 ( 20) [-22 57] 17 ( 20) [-22 57]
12 190 107 ( 17) 196 75 ( 17) 33 ( 24) [-14 79] 32 ( 24) [-15 78]
50
24 193 143 ( 17) 194 125 ( 17) 18 ( 25) [-30 67] 18 ( 25) [-31 66]
48 187 177 ( 19) 193 171 ( 19) 5 ( 27) [-48 58] 4 ( 27) [-49 57]
72 193 230 ( 22) 191 213 ( 22) 17 ( 31) [-45 79] 18 ( 31) [-44 79]
96 185 228 ( 24) 189 202 ( 24) 26 ( 34) [-41 93] 27 ( 34) [-39 93]
Average treatment differences through follow-up+ 21 ( 20) [-17, 59] 20 ( 19) [-18, 58]
*Change calculated using normal regression adjusting for baseline and in total ODYSSEY A and B strata only. Presenting mean change from a baseline of 521.8 in total, 487.4 in A, and
548.8 in B.
**Normal regression also adjusted for all stratification factors in addition to baseline CD4 count
+Linear mixed models fitted with random intercept and fixed effects for treatment group, study visit and adjustment covariates (baseline CD4 count and stratification factors)
Figure S8.1 Total population - Changes in CD4 count over follow-up
51
Figure S8.2 ODYSSEY A - changes in CD4 count over follow-up
52
Figure S8.3 ODYSSEY B - changes in CD4 count over follow-up
Table S8.4 Total population - Changes in CD4 percentage over follow-up

4 346 2.9 (0.3) 349 1.9 (0.3) 1.0 (0.4) [0.2, 1.7] 1.0 (0.4) [0.3, 1.7]
12 341 3.8 (0.3) 348 3.0 (0.3) 0.7 (0.4) [-0.0, 1.5] 0.8 (0.4) [0.0, 1.5]
24 343 5.6 (0.3) 344 4.8 (0.3) 0.8 (0.5) [-0.1, 1.7] 0.8 (0.5) [-0.1, 1.7]
48 332 7.7 (0.4) 338 7.2 (0.4) 0.5 (0.5) [-0.5, 1.5] 0.5 (0.5) [-0.4, 1.5]
72 341 9.6 (0.4) 336 8.2 (0.4) 1.4 (0.6) [0.3, 2.5] 1.5 (0.6) [0.4, 2.6]
96 334 10.2 (0.5) 328 9.2 (0.5) 0.9 (0.7) [-0.4, 2.2] 0.9 (0.7) [-0.4, 2.3]
Average treatment differences through follow-up+ 0.9 (0.4) [0.2, 1.6] 0.9 (0.4) [0.2, 1.6]
53
Table S8.5 ODYSSEY A - changes in CD4 percentage over follow-up

4 154 4.4 (0.4) 151 4.2 (0.4) 0.3 (0.5) [-0.7 1.3] 0.3 (0.5) [-0.7 1.3]
12 151 5.7 (0.4) 152 5.1 (0.4) 0.6 (0.6) [-0.6 1.7] 0.6 (0.6) [-0.5 1.7]
24 150 7.3 (0.5) 150 6.4 (0.5) 0.9 (0.7) [-0.5 2.3] 0.9 (0.7) [-0.5 2.3]
48 145 9.6 (0.5) 145 9.1 (0.5) 0.5 (0.7) [-1.0 1.9] 0.6 (0.7) [-0.8 2.0]
72 148 11.5 (0.6) 145 10.4 (0.6) 1.1 (0.8) [-0.5 2.7] 1.1 (0.8) [-0.4 2.7]
96 149 12.4 (0.6) 139 11.4 (0.6) 1.0 (0.8) [-0.6 2.7] 1.1 (0.8) [-0.6 2.7]
Average treatment differences through follow-up+ 0.8 (0.5) [-0.2, 1.8] 0.8 (0.5) [-0.2, 1.8]
Table S8.6 ODYSSEY B - changes in CD4 percentage over follow-up

4 192 1.7 (0.4) 198 0.3 (0.4) 1.4 (0.5) [0.4 2.4] 1.4 (0.5) [0.4 2.4]
12 190 2.2 (0.3) 196 1.5 (0.3) 0.8 (0.5) [-0.2 1.7] 0.8 (0.5) [-0.1 1.7]
24 193 4.2 (0.4) 194 3.6 (0.4) 0.7 (0.6) [-0.5 1.8] 0.7 (0.6) [-0.5 1.8]
48 187 6.2 (0.5) 193 5.6 (0.5) 0.5 (0.7) [-0.8 1.8] 0.5 (0.7) [-0.8 1.8]
72 193 8.2 (0.5) 191 6.5 (0.6) 1.7 (0.8) [0.2 3.2] 1.7 (0.8) [0.2 3.2]
96 185 8.4 (0.7) 189 7.5 (0.7) 0.8 (1.0) [-1.2 2.9] 0.8 (1.0) [-1.2 2.8]
*Change calculated using normal regression adjusting for baseline and in total ODYSSEY A and B strata only. Presenting mean change from a baseline of 21.4 in total, 19.4 in A, and 22.9
in B.
**Normal regression also adjusted for all stratification factors in addition to baseline CD4 percentage
+Linear mixed models fitted with random intercept and fixed effects for treatment group, study visit and adjustment covariates (baseline CD4 percentage and stratification factors)
54
Figure S8.4 Total population - Changes in CD4 percentage over follow-up
55
Figure S8.5 ODYSSEY A - changes in CD4 percentage over follow-up
56
Figure 8.6 ODYSSEY B - changes in CD4 percentage over follow-up
Table S8.7 Total population - Changes in CD4/CD8 ratio over follow-up

4 340 0.08 (0.04) 341 0.04 (0.04) 0.04 (0.06) [-0.08, 0.16] 0.04 (0.06) [-0.08, 0.16]
12 336 0.08 (0.07) 340 0.18 (0.07) -0.10 (0.09) [-0.29, 0.08] -0.10 (0.09) [-0.28, 0.08]
24 343 0.16 (0.03) 344 0.19 (0.03) -0.04 (0.04) [-0.11, 0.04] -0.04 (0.04) [-0.11, 0.04]
48 332 0.35 (0.08) 338 0.28 (0.08) 0.07 (0.11) [-0.15, 0.30] 0.07 (0.11) [-0.15, 0.30]
72 341 0.49 (0.12) 336 0.36 (0.12) 0.13 (0.17) [-0.20, 0.45] 0.13 (0.17) [-0.20, 0.46]
96 334 0.35 (0.03) 328 0.37 (0.03) -0.01 (0.04) [-0.08, 0.06] -0.01 (0.04) [-0.08, 0.06]
57
Table S8.8 ODYSSEY A - changes in CD4/CD8 ratio over follow-up

4 148 0.19 (0.10) 145 0.10 (0.10) 0.09 (0.14) [-0.17 0.36] 0.09 (0.14) [-0.17 0.36]
12 146 0.13 (0.15) 146 0.36 (0.15) -0.23 (0.21) [-0.65 0.19] -0.21 (0.21) [-0.63 0.20]
24 150 0.22 (0.04) 150 0.22 (0.04) 0.00 (0.06) [-0.11 0.12] 0.01 (0.06) [-0.10 0.12]
48 145 0.31 (0.04) 145 0.33 (0.04) -0.02 (0.06) [-0.13 0.09] -0.01 (0.05) [-0.12 0.10]
72 148 0.77 (0.26) 145 0.38 (0.27) 0.38 (0.38) [-0.35 1.12] 0.39 (0.38) [-0.35 1.13]
96 149 0.43 (0.04) 139 0.42 (0.04) 0.01 (0.06) [-0.11 0.12] 0.01 (0.06) [-0.10 0.12]
Table S8.9 ODYSSEY B - changes in CD4/CD8 ratio over follow-up

4 192 -0.00 (0.03) 196 -0.00 (0.03) -0.00 (0.04) [-0.07 0.07] -0.00 (0.04) [-0.07 0.07]
12 190 0.04 (0.03) 194 0.04 (0.03) 0.00 (0.04) [-0.08 0.08] 0.00 (0.04) [-0.08 0.08]
24 193 0.11 (0.03) 194 0.17 (0.03) -0.06 (0.05) [-0.16 0.03] -0.06 (0.05) [-0.16 0.03]
48 187 0.39 (0.14) 193 0.24 (0.14) 0.15 (0.20) [-0.24 0.53] 0.15 (0.20) [-0.24 0.53]
72 193 0.28 (0.05) 191 0.34 (0.05) -0.06 (0.07) [-0.20 0.09] -0.05 (0.07) [-0.19 0.09]
96 185 0.30 (0.03) 189 0.32 (0.03) -0.02 (0.05) [-0.12 0.07] -0.02 (0.05) [-0.11 0.07]
*Change calculated using normal regression adjusting for baseline and in total ODYSSEY A and B strata only. Presenting mean change from a baseline of 0.5 in total, 0.5 in A, and 0.6 in
B.
**Normal regression also adjusted for all stratification factors in addition to baseline CD4/CD8 ratio
+Linear mixed models fitted with random intercept and fixed effects for treatment group, study visit and adjustment covariates (baseline CD4/CD8 ratio and stratification factors)
58
Figure S8.7 Total population - Changes in CD4/CD8 ratio over follow-up
59
Figure S8.8 ODYSSEY A - changes in CD4/CD8 ratio over follow-up
60
Figure S8.9 ODYSSEY B - changes in CD4/CD8 ratio over follow-up
61
S 9 Lipids
data at baseline.
Table S9.1 Total population - Total cholesterol changes over follow-up

48 342 -5.4 (1.4) 337 10.2 (1.4) -15.8 (1.9) [-19.6, -12.0] -15.9 (1.9) [-19.7, -12.1]
96 340 -5.0 (1.5) 332 9.9 (1.5) -15.0 (2.0) [-19.0, -11.0] -15.1 (2.0) [-19.0, -11.1]
144 157 -2.3 (2.5) 153 11.1 (2.5) -13.4 (3.5) [-20.3, -6.6] -13.7 (3.4) [-20.4, -6.9]
Average treatment differences through follow-up+ -15.0 (1.7) [-18.3, -11.7] -15.1 (1.7) [-18.3, -11.8]
Table S9.2 ODYSSEY A - Total cholesterol changes over follow-up

48 151 3.2 (2.1) 146 20.0 (2.2) -16.9 (3.1) [-22.9, -10.8] -17.1 (3.0) [-23.0, -11.3]
96 148 2.1 (2.3) 140 19.6 (2.3) -17.5 (3.3) [-24.0, -11.1] -17.5 (3.2) [-23.9, -11.1]
144 81 1.7 (3.5) 79 15.8 (3.5) -14.1 (4.9) [-23.8, -4.4] -14.6 (4.8) [-24.1, -5.1]
Table S9.3 ODYSSEY B - Total cholesterol changes over follow-up

48 191 -12.2 (1.8) 191 2.9 (1.8) -15.0 (2.5) [-20.0, -10.1] -14.9 (2.5) [-19.8, -10.0]
96 192 -10.5 (1.8) 192 2.8 (1.8) -13.3 (2.6) [-18.5, -8.2] -13.4 (2.6) [-18.5, -8.4]
144 76 -6.5 (3.4) 74 6.3 (3.5) -12.8 (4.9) [-22.5, -3.2] -12.7 (4.9) [-22.4, -2.9]
141.1 in B.
**Normal regression also adjusted for all stratification factors in addition to baseline Total cholesterol
+Linear mixed models fitted with random intercept and fixed effects for treatment group, study visit and adjustment covariates (baseline Total cholesterol and stratification factors)
62
Figure S9.1Total population - changes in Total cholesterol over follow-up
63
Figure S9.2 ODYSSEY A - changes in Total cholesterol over follow-up
64
Figure S9.3 ODYSSEY B - changes in Total cholesterol over follow-up
Table S9.4 Total population - LDL cholesterol changes over follow-up

48 336 -4.8 (1.2) 335 1.9 (1.2) -6.8 (1.7) [-10.2, -3.4] -6.8 (1.7) [-10.2, -3.5]
96 334 -3.6 (1.3) 326 5.3 (1.3) -9.0 (1.8) [-12.6, -5.4] -9.1 (1.8) [-12.6, -5.5]
144 155 -1.3 (2.0) 148 4.9 (2.1) -6.1 (2.9) [-11.8, -0.4] -6.4 (2.8) [-12.0, -0.9]
65
Table S9.5 ODYSSEY A - LDL cholesterol changes over follow-up

48 149 -1.7 (1.9) 145 7.9 (1.9) -9.6 (2.7) [-14.9, -4.3] -9.8 (2.7) [-15.1, -4.6]
96 147 -0.4 (2.0) 140 10.9 (2.0) -11.3 (2.9) [-16.9, -5.7] -11.3 (2.8) [-16.9, -5.8]
144 80 1.3 (3.0) 78 8.0 (3.0) -6.8 (4.2) [-15.2, 1.6] -7.2 (4.0) [-15.0, 0.7]
Table S9.6 ODYSSEY B - LDL cholesterol changes over follow-up

48 187 -7.3 (1.6) 190 -2.6 (1.6) -4.6 (2.2) [-9.0, -0.2] -4.5 (2.2) [-8.8, -0.1]
96 187 -6.1 (1.7) 186 1.2 (1.7) -7.3 (2.4) [-11.9, -2.6] -7.4 (2.4) [-12.0, -2.7]
144 75 -3.6 (2.7) 70 1.9 (2.8) -5.4 (3.9) [-13.2, 2.3] -5.6 (3.9) [-13.4, 2.2]
in B.
**Normal regression also adjusted for all stratification factors in addition to baseline LDL cholesterol
+Linear mixed models fitted with random intercept and fixed effects for treatment group, study visit and adjustment covariates (baseline LDL cholesterol and stratification factors)
66
Figure S9.4 Total population - changes in LDL cholesterol over follow-up
67
Figure S9.5 ODYSSEY A - changes in LDL cholesterol over follow-up
68
Figure S9.6 ODYSSEY B - changes in LDL cholesterol over follow-up
Table S9.7 Total population - HDL cholesterol changes over follow-up

48 317 3.0 (0.8) 324 6.8 (0.7) -3.9 (1.0) [-5.9, -1.8] -3.8 (1.0) [-5.9, -1.8]
96 318 4.0 (0.8) 312 8.2 (0.8) -4.3 (1.1) [-6.5, -2.1] -4.1 (1.1) [-6.2, -2.0]
144 156 5.1 (1.3) 152 9.6 (1.3) -4.5 (1.8) [-8.0, -1.0] -4.2 (1.8) [-7.7, -0.8]
69
Table S9.8 ODYSSEY A - HDL cholesterol changes over follow-up

48 146 7.2 (1.1) 142 13.0 (1.1) -5.9 (1.6) [-9.0, -2.7] -5.8 (1.6) [-8.9, -2.7]
96 142 9.2 (1.2) 135 14.2 (1.2) -5.1 (1.7) [-8.5, -1.6] -4.9 (1.7) [-8.3, -1.5]
144 80 10.8 (1.8) 79 14.7 (1.8) -4.0 (2.6) [-9.1, 1.2] -3.7 (2.5) [-8.7, 1.3]
Table S9.9 ODYSSEY B - HDL cholesterol changes over follow-up

48 171 -0.3 (1.0) 182 2.0 (0.9) -2.3 (1.4) [-4.9, 0.4] -2.3 (1.4) [-4.9, 0.4]
96 176 -0.1 (1.0) 177 3.5 (1.0) -3.6 (1.4) [-6.5, -0.8] -3.4 (1.4) [-6.2, -0.7]
144 76 -0.2 (1.7) 73 4.9 (1.7) -5.1 (2.4) [-9.9, -0.3] -4.8 (2.4) [-9.6, -0.0]
in B.
**Normal regression also adjusted for all stratification factors in addition to baseline HDL cholesterol
+Linear mixed models fitted with random intercept and fixed effects for treatment group, study visit and adjustment covariates (baseline HDL cholesterol and stratification factors)
70
Figure S9.7 Total population - changes in HDL cholesterol over follow-up
71
Figure S9.8 ODYSSEY A - changes in HDL cholesterol over follow-up
72
Figure S9.9 ODYSSEY B - changes in HDL cholesterol over follow-up
Table S9.10 Total population - Triglycerides changes over follow-up

48 342 -6.3 (2.6) 337 13.2 (2.7) -19.5 (3.7) [-26.8, -12.2] -19.7 (3.7) [-27.0, -12.4]
96 340 -6.7 (2.7) 333 14.6 (2.8) -21.2 (3.9) [-28.8, -13.7] -21.5 (3.8) [-28.9, -14.1]
144 151 -9.1 (4.0) 148 17.3 (4.1) -26.4 (5.7) [-37.7, -15.2] -25.7 (5.7) [-36.9, -14.5]
73
Table S9.11 ODYSSEY A - Triglycerides changes over follow-up

48 150 -2.0 (4.3) 146 7.0 (4.4) -9.0 (6.2) [-21.2, 3.1] -9.4 (6.1) [-21.4, 2.6]
96 148 -13.4 (3.6) 141 6.2 (3.7) -19.6 (5.2) [-29.9, -9.4] -19.8 (5.1) [-29.9, -9.7]
144 79 -12.3 (4.4) 77 9.6 (4.5) -21.9 (6.3) [-34.4, -9.4] -22.2 (6.4) [-34.9, -9.6]
Table S9.12 ODYSSEY B - Triglycerides changes over follow-up

48 192 -9.5 (3.3) 191 17.7 (3.3) -27.2 (4.6) [-36.3, -18.2] -27.3 (4.6) [-36.3, -18.2]
96 192 -1.7 (3.9) 192 20.5 (3.9) -22.2 (5.5) [-33.0, -11.4] -22.4 (5.3) [-32.9, -12.0]
144 72 -6.3 (6.8) 71 26.4 (6.9) -32.7 (9.7) [-51.9, -13.5] -30.5 (9.7) [-49.6, -11.4]
in B.
**Normal regression also adjusted for all stratification factors in addition to baseline Triglycerides
+Linear mixed models fitted with random intercept and fixed effects for treatment group, study visit and adjustment covariates (baseline Triglycerides and stratification factors)
74
Figure S9.10 Total population - changes in Triglycerides over follow-up
75
Figure S9.11 ODYSSEY A - changes in Triglycerides over follow-up
76
Figure S9.12 ODYSSEY B - changes in Triglycerides over follow-up
77
S 10 Adverse events
Table S10.1 Serious Adverse Events (SAEs) to trial censoring date by SAE type*
Total A B
Number of events [Number of participants] 65 [35] 44 [40] 109 [75] 52 [23] 31 [27] 83 [50] 13 [12] 13 [13] 26 [25]
Death 2 [2] 3 [3] 5 [5] 2 [2] 2 [2] 4 [4] 0 [0] 1 [1] 1 [1]
Life-threatening 6 [3] 1 [1] 7 [4] 6 [3] 1 [1] 7 [4] 0 [0] 0 [0] 0 [0]
Hospitalisation 52 [30] 39 [35] 91 [65] 40 [19] 27 [23] 67 [42] 12 [11] 12 [12] 24 [23]
Significant disability 2 [2] 0 [0] 2 [2] 2 [2] 0 [0] 2 [2] 0 [0] 0 [0] 0 [0]
Other 3 [3] 1 [1] 4 [4] 2 [2] 1 [1] 3 [3] 1 [1] 0 [0] 1 [1]
*Non-overlapping categories, worst taken.
Table S10.2 Serious Adverse Events to trial censoring date

Total A B
Person years 943 933 1875 418 408 826 524 525 1049
Number of events [Number of young people] 65 [35] 44 [40] 109 [75] 52 [23] 31 [27] 83 [50] 13 [12] 13 [13] 26 [25]
Biochemical 2 [2] 0 [0] 2 [2] 2 [2] 0 [0] 2 [2] 0 [0] 0 [0] 0 [0]
Hyperkalaemia 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Raised creatinine 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Cardiovascular 3 [2] 0 [0] 3 [2] 3 [2] 0 [0] 3 [2] 0 [0] 0 [0] 0 [0]
Congestive cardiac failure 2 [1] 0 [0] 2 [1] 2 [1] 0 [0] 2 [1] 0 [0] 0 [0] 0 [0]
Deep vein thrombosis 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Haematological 12 [3] 4 [3] 16 [6] 10 [1] 2 [1] 12 [2] 2 [2] 2 [2] 4 [4]
Anaemia with clinical symptoms 11 [2] 4 [3] 15 [5] 10 [1] 2 [1] 12 [2] 1 [1] 2 [2] 3 [3]
Thrombocytopenia+Neutropenia 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
Hepatic 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Drug induced liver injury 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Immune System Disorder 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Hypersensitivity reaction 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Acute diarrhoea not investigated 1 [1] 1 [1] 2 [2] 1 [1] 1 [1] 2 [2] 0 [0] 0 [0] 0 [0]
Acute diarrhoea not investigated+Renal 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
failure - acute+Thrombocytopenia
Acute febrile episode - undiagnosed 3 [3] 1 [1] 4 [4] 3 [3] 1 [1] 4 [4] 0 [0] 0 [0] 0 [0]
Acute parotitis 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Acute sinusitis 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
78
Appendicitis 0 [0] 2 [1] 2 [1] 0 [0] 2 [1] 2 [1] 0 [0] 0 [0] 0 [0]
Bronchiectasis infectious exacerbation 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1]
Chest infection 1 [1] 1 [1] 2 [2] 1 [1] 0 [0] 1 [1] 0 [0] 1 [1] 1 [1]
Cutaneous warts, Human Papillomavirus 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Gastroenteritis 1 [1] 2 [2] 3 [3] 1 [1] 2 [2] 3 [3] 0 [0] 0 [0] 0 [0]
Herpes encephalitis 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Measles 1 [1] 1 [1] 2 [2] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1] 2 [2]
Other Gram-positive sepsis 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Plasmodium falciparum malaria 5 [3] 0 [0] 5 [3] 4 [2] 0 [0] 4 [2] 1 [1] 0 [0] 1 [1]
Pneumonia - other bacterial 2 [2] 4 [4] 6 [6] 2 [2] 1 [1] 3 [3] 0 [0] 3 [3] 3 [3]
Pneumonia - other bacterial+Presumed 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
septicaemia/bacteremia - not investigated *
Pneumonia no organism identified 0 [0] 4 [4] 4 [4] 0 [0] 2 [2] 2 [2] 0 [0] 2 [2] 2 [2]
Pneumonia no organism 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
identified+Candidiasis of oesophagus, trachea,
bronchi or lungs
+Tuberculosis - pulmonary - smear negative or
not done
Presumed septicaemia/bacteremia - no 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1]
organism
organism+Tuberculosis - disseminated
Septic abortion 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
Septic arthritis+Uveitis 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Skin abscess 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
Tuberculosis - pulmonary - smear positive 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Lower respiratory tract 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Pneumothorax+bronchiolitis obliterans 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Musculoskeletal 2 [2] 1 [1] 3 [3] 1 [1] 1 [1] 2 [2] 1 [1] 0 [0] 1 [1]
Bone fracture 2 [2] 1 [1] 3 [3] 1 [1] 1 [1] 2 [2] 1 [1] 0 [0] 1 [1]
Nervous System 4 [3] 4 [4] 8 [7] 2 [2] 4 [4] 6 [6] 2 [1] 0 [0] 2 [1]
Dizziness 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Epilepsy, fits, convulsions 3 [2] 3 [3] 6 [5] 1 [1] 3 [3] 4 [4] 2 [1] 0 [0] 2 [1]
Headache+Hypertension 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Non HIV related deaths 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Traumatic+Cutaneous warts, Human 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Papillomavirus
Oral 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Mouth ulcers 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Pregnancy associated 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Spontaneous abortion (complete or 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
79
incomplete)
Psychiatric 3 [2] 2 [2] 5 [4] 3 [2] 2 [2] 5 [4] 0 [0] 0 [0] 0 [0]
Depression 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Parasuicide (suicide attempt) 1 [1] 2 [2] 3 [3] 1 [1] 2 [2] 3 [3] 0 [0] 0 [0] 0 [0]
Psychosis, mania 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Renal 3 [2] 0 [0] 3 [2] 3 [2] 0 [0] 3 [2] 0 [0] 0 [0] 0 [0]
Renal failure - acute 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Renal failure - chronic 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Skin 2 [2] 1 [1] 3 [3] 1 [1] 1 [1] 2 [2] 1 [1] 0 [0] 1 [1]
Burns 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
Rash, erythematous 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Rash, maculopapular+URTI - acute 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Systemic 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Kwashiorkor 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Tumours 1 [1] 2 [2] 3 [3] 0 [0] 1 [1] 1 [1] 1 [1] 1 [1] 2 [2]
Hodgkin lymphoma 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1]
Other 0 [0] 2 [2] 2 [2] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1]
Non-fatal trauma 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Reviewed to date (of reported) 65 (100%) 44 (100%) 109 (100%) 52 (100%) 31 (100%) 83 (100%) 13 (100%) 13 (100%) 26 (100%)
(95% CI) (5.4, 8.8) (3.5, 6.3) (4.8, 7.0) (9.5, 16.3) (5.3, 10.8) (8.1, 12.5) (1.4, 4.3) (1.4, 4.3) (1.7, 3.6)
Rate ratio** 1.45 1 (ref) 1.64 1 (ref) 1.00 1 (ref)
(95% CI) (0.80, 2.63) - (0.79, 3.40) - (0.46, 2.18)
P-value 0.223 0.186 0.998
Adj. Rate ratio*** 1.45 1 (ref) 1.63 1 (ref) 1.01 1 (ref)
(95% CI) (0.81, 2.59) - (0.80, 3.31) - (0.46, 2.20)
P-value 0.215 0.181 0.982
Time to first event
Hazard ratio** 0.87 1 (ref) 0.84 1 (ref) 0.93 1 (ref)
(95% CI) (0.55, 1.36) - (0.48, 1.46) - (0.42, 2.03) -
P-value 0.531 0.529 0.849
Adj. hazard ratio*** 0.87 1 (ref) 0.83 1 (ref) 0.93 1 (ref)
(95% CI) (0.55, 1.36) - (0.48, 1.46) - (0.42, 2.04) -
P-value 0.534 0.524 0.858
A/B x arm interaction 0.8226
*Resulted in death
**Adjusted for ODYSSEY A and B strata in total. Unadjusted in A and B comparison.
80
***Adjusted for all stratification factors.
Table S10.3 Grade 3 or above clinical and laboratory adverse events to trial censoring date
Total A B
Person years 943 933 1875 418 408 826 524 525 1049
Number of events [Number of young 113 [73] 132 [86] 245 [159] 80 [48] 62 [43] 142 [91] 33 [25] 70 [43] 103 [68]
people]
Biochemical 17 [16] 51 [35] 68 [51] 11 [10] 10 [9] 21 [19] 6 [6] 41 [26] 47 [32]
Hyperkalaemia 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Hypocalcaemia - asymptomatic 2 [2] 5 [5] 7 [7] 2 [2] 1 [1] 3 [3] 0 [0] 4 [4] 4 [4]
Hypocalcaemia - clinically 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
symptomatic
Hypophosphataemia 1 [1] 1 [1] 2 [2] 1 [1] 0 [0] 1 [1] 0 [0] 1 [1] 1 [1]
Proteinuria 2 [2] 0 [0] 2 [2] 0 [0] 0 [0] 0 [0] 2 [2] 0 [0] 2 [2]
Raised ALT 1 [1] 2 [2] 3 [3] 1 [1] 2 [2] 3 [3] 0 [0] 0 [0] 0 [0]
Raised AST 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Raised LDL 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Raised bilirubin 2 [2] 37 [24] 39 [26] 1 [1] 3 [2] 4 [3] 1 [1] 34 [22] 35 [23]
Raised liver enzymes 2 [2] 1 [1] 3 [3] 0 [0] 1 [1] 1 [1] 2 [2] 0 [0] 2 [2]
Raised tryglycerides 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1]
raised low density lipoprotein 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Cardiovascular 3 [3] 0 [0] 3 [3] 3 [3] 0 [0] 3 [3] 0 [0] 0 [0] 0 [0]
Hypertension 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Eye 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Uveitis 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Haematological 33 [29] 28 [23] 61 [52] 20 [19] 15 [14] 35 [33] 13 [10] 13 [9] 26 [19]
Anaemia with no clinical symptoms 8 [8] 8 [5] 16 [13] 6 [6] 5 [4] 11 [10] 2 [2] 3 [1] 5 [3]
Low lymphocytes 1 [1] 1 [1] 2 [2] 1 [1] 1 [1] 2 [2] 0 [0] 0 [0] 0 [0]
Neutropenia 11 [9] 7 [7] 18 [16] 8 [7] 5 [5] 13 [12] 3 [2] 2 [2] 5 [4]
Thrombocytopenia 9 [8] 8 [8] 17 [16] 2 [2] 3 [3] 5 [5] 7 [6] 5 [5] 12 [11]
Hepatic 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
drug induced liver injury 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
81
Acute sinusitis 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
Appendicitis 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Bronchiectasis infectious 0 [0] 2 [1] 2 [1] 0 [0] 0 [0] 0 [0] 0 [0] 2 [1] 2 [1]
exacerbation
Candidiasis of oesophagus, trachea, 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
bronchi or lungs
Chest infection 1 [1] 1 [1] 2 [2] 1 [1] 0 [0] 1 [1] 0 [0] 1 [1] 1 [1]
Chronic diarrhoea not investigated 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Gingivitis, bleeding gums, 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
periodontitis, stomatitis - not necrotizing
Hepatitis A 3 [3] 0 [0] 3 [3] 1 [1] 0 [0] 1 [1] 2 [2] 0 [0] 2 [2]
Herpes Zoster (Varicella Zoster) - 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
cutaneous
Measles 1 [1] 1 [1] 2 [2] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1] 2 [2]
Oral candida 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Other Gram-positive sepsis 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Pneumonia - other bacterial * 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Pneumonia - other organism (not 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1]
bacterial)
Presumed septicaemia/bacteremia - 0 [0] 2 [2] 2 [2] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1]
no organism
Presumed septicaemia/bacteremia - 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
not investigated *
Septic abortion 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
Septic arthritis 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Skin abscess 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
Tuberculosis - pulmonary - smear 4 [4] 0 [0] 4 [4] 4 [4] 0 [0] 4 [4] 0 [0] 0 [0] 0 [0]
negative or not done
positive
Pneumothorax 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Bone fracture 2 [2] 2 [2] 4 [4] 1 [1] 1 [1] 2 [2] 1 [1] 1 [1] 2 [2]
Nervous System 6 [6] 5 [5] 11 [11] 4 [4] 4 [4] 8 [8] 2 [2] 1 [1] 3 [3]
Dizziness 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
82
Headache 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
dystonia 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Traumatic 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Oral 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Mouth ulcers 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
incomplete)
Psychiatric 6 [4] 3 [3] 9 [7] 5 [3] 2 [2] 7 [5] 1 [1] 1 [1] 2 [2]
Depression 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Insomnia 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Psychosis, mania 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Suicidal Ideation 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
Renal 3 [3] 0 [0] 3 [3] 3 [3] 0 [0] 3 [3] 0 [0] 0 [0] 0 [0]
Skin 1 [1] 1 [1] 2 [2] 0 [0] 1 [1] 1 [1] 1 [1] 0 [0] 1 [1]
Burns 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
Systemic 1 [1] 1 [1] 2 [2] 1 [1] 1 [1] 2 [2] 0 [0] 0 [0] 0 [0]
Kwashiorkor 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Wasting syndrome uninvestigated 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Tumours 0 [0] 2 [2] 2 [2] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1]
Hodgkin lymphoma 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1]
Other 0 [0] 2 [2] 2 [2] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1]
Non-fatal trauma 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Clinical (or labs reported by site) events 91 (100%) 93 (100%) 184 (100%) 64 (100%) 48 (100%) 112 (100%) 27 (100%) 45 (100%) 72 (100%)
reviewed by ERC
Events identified from routine labs (Not 22 (19%) 39 (30%) 61 (25%) 16 (20%) 14 (23%) 30 (21%) 6 (18%) 25 (36%) 31 (30%)
ERCd), N (% of total events)
Asymtomatic lab events, N (% of total 41 (36%) 63 (48%) 104 (42%) 26 (33%) 21 (34%) 47 (33%) 15 (45%) 42 (60%) 57 (55%)
events)
(95% CI) (10.0, 14.4) (11.9, 16.8) (11.5, 14.8) (15.4, 23.8) (11.8, 19.5) (14.6, 20.3) (4.5, 8.9) (10.6, 16.9) (8.1, 11.9)
(95% CI) (0.60, 1.18) - (0.81, 1.96) - (0.28, 0.79) -
P-value 0.323 0.309 0.004
(95% CI) (0.61, 1.18) - (0.81, 1.97) - (0.28, 0.79) -
P-value 0.323 0.298 0.004
83
Time to first event

(95% CI) (0.61, 1.14) - (0.74, 1.69) - (0.34, 0.90) -
P-value 0.245 0.589 0.017
(95% CI) (0.61, 1.13) - (0.75, 1.70) - (0.33, 0.88) -
P-value 0.238 0.569 0.014
*Resulted in death
Table S10.4 Adverse events leading to ART modification (any grade) to trial censoring date
Total A B
Person years 943 933 1875 418 408 826 524 525 1049
Number of events [Number of young people+] 6 [5] 17 [17] 23 [22] 4 [3] 8 [8] 12 [11] 2 [2] 9 [9] 11 [11]
Biochemical 0 [0] 4 [4] 4 [4] 0 [0] 0 [0] 0 [0] 0 [0] 4 [4] 4 [4]
Haematological 1 [1] 4 [4] 5 [5] 0 [0] 0 [0] 0 [0] 1 [1] 4 [4] 5 [5]
Neutropenia 0 [0] 2 [2] 2 [2] 0 [0] 0 [0] 0 [0] 0 [0] 2 [2] 2 [2]
Hepatitis A 2 [2] 0 [0] 2 [2] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1]
Nervous System 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Dizziness^ 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Psychiatric 2 [2] 1 [1] 3 [3] 2 [2] 1 [1] 3 [3] 0 [0] 0 [0] 0 [0]
Depression 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Psychosis, mania 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Skin 0 [0] 4 [4] 4 [4] 0 [0] 4 [4] 4 [4] 0 [0] 0 [0] 0 [0]
Gynaecomastia 0 [0] 2 [2] 2 [2] 0 [0] 2 [2] 2 [2] 0 [0] 0 [0] 0 [0]
84
(95% CI) (0.3, 1.4) (1.1, 2.9) (0.8, 1.8) (0.4, 2.5) (1.0, 3.9) (0.8, 2.6) (0.1, 1.5) (0.9, 3.3) (0.6, 1.9)
Rate ratio* 0.35 1 (ref) 0.49 1 (ref) 0.22 1 (ref)
(95% CI) (0.12, 0.97) - (0.12, 1.91) - (0.05, 1.02) -
P-value 0.044 0.303 0.053
Adj. Rate ratio** 0.35 1 (ref) 0.47 1 (ref) 0.23 1 (ref)
(95% CI) (0.13, 0.95) - (0.12, 1.82) - (0.05, 1.03) -
P-value 0.040 0.274 0.055
Time to first event
Hazard ratio* 0.29 1 (ref) 0.37 1 (ref) 0.22 1 (ref)
(95% CI) (0.11, 0.79) - (0.10, 1.38) - (0.05, 1.03) -
P-value 0.015 0.138 0.054
Adj. hazard ratio** 0.29 1 (ref) 0.35 1 (ref) 0.22 1 (ref)
(95% CI) (0.11, 0.77) - (0.09, 1.33) - (0.05, 1.03) -
P-value 0.014 0.125 0.055
+One participant (DTG) switched ART on two occasions, the first was due to a hypersensitivity reaction and then switched again due to depression.
*Adjusted for ODYSSEY A and B strata in total. Unadjusted in A and B comparison.
**Adjusted for all stratification factors.
^One participant had a decrease in EFV due to dizziness, however, given that this is not a change in drug, this participant is categorised as remaining on their strict initial regimen in the
table summarising ART substitutions.
Table S10.5 Serious Adverse Events (SAEs) to week 96 by SAE type*

Total A B
Number of events [Number of participants] 49 [29] 37 [33] 86 [62] 38 [19] 26 [22] 64 [41] 11 [10] 11 [11] 22 [21]
Death 1 [1] 3 [3] 4 [4] 1 [1] 2 [2] 3 [3] 0 [0] 1 [1] 1 [1]
Life-threatening 4 [2] 0 [0] 4 [2] 4 [2] 0 [0] 4 [2] 0 [0] 0 [0] 0 [0]
Hospitalisation 40 [24] 33 [29] 73 [53] 30 [15] 23 [19] 53 [34] 10 [9] 10 [10] 20 [19]
Significant disability 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Other 3 [3] 1 [1] 4 [4] 2 [2] 1 [1] 3 [3] 1 [1] 0 [0] 1 [1]
*Non-overlapping categories, worst taken.
85
Table S10.6 Serious Adverse Events to week 96

Total A B
Person years 635 634 1269 279 273 552 357 361 718
Number of events [Number of young people] 49 [29] 37 [33] 86 [62] 38 [19] 26 [22] 64 [41] 11 [10] 11 [11] 22 [21]
Biochemical 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Cardiovascular 2 [2] 0 [0] 2 [2] 2 [2] 0 [0] 2 [2] 0 [0] 0 [0] 0 [0]
Haematological 12 [3] 3 [2] 15 [5] 10 [1] 2 [1] 12 [2] 2 [2] 1 [1] 3 [3]
Thrombocytopenia+Neutropenia 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
Hepatic 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Acute diarrhoea not investigated+Renal 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
failure - acute+Thrombocytopenia
Acute parotitis 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Acute sinusitis 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
Appendicitis 0 [0] 2 [1] 2 [1] 0 [0] 2 [1] 2 [1] 0 [0] 0 [0] 0 [0]
Bronchiectasis infectious exacerbation 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1]
Chest infection 1 [1] 1 [1] 2 [2] 1 [1] 0 [0] 1 [1] 0 [0] 1 [1] 1 [1]
Cutaneous warts, Human Papillomavirus 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Measles 1 [1] 1 [1] 2 [2] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1] 2 [2]
Pneumonia - other bacterial+Presumed 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
septicaemia/bacteremia - not investigated *
+Candidiasis of oesophagus, trachea, bronchi or
lungs
+Tuberculosis - pulmonary - smear negative or not
86
done
organism
organism+Tuberculosis - disseminated
Septic arthritis+Uveitis 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Skin abscess 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
Pneumothorax+bronchiolitis obliterans 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Bone fracture 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
Nervous System 4 [3] 1 [1] 5 [4] 2 [2] 1 [1] 3 [3] 2 [1] 0 [0] 2 [1]
Headache+Hypertension 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Traumatic+Cutaneous warts, Human 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Papillomavirus
Oral 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Mouth ulcers 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
incomplete)
Psychiatric 1 [1] 1 [1] 2 [2] 1 [1] 1 [1] 2 [2] 0 [0] 0 [0] 0 [0]
Psychosis, mania 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Renal 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Skin 2 [2] 1 [1] 3 [3] 1 [1] 1 [1] 2 [2] 1 [1] 0 [0] 1 [1]
Burns 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
Rash, maculopapular+URTI - acute 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Systemic 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Kwashiorkor 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Tumours 1 [1] 1 [1] 2 [2] 0 [0] 1 [1] 1 [1] 1 [1] 0 [0] 1 [1]
Other 0 [0] 2 [2] 2 [2] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1]
Non-fatal trauma 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
(95% CI) (5.8, 10.2) (4.2, 8.1) (5.5, 8.4) (9.9, 18.7) (6.5, 14.0) (9.1, 14.8) (1.7, 5.6) (1.7, 5.5) (2.0, 4.7)
87

(95% CI) (0.66, 2.58) - (0.61, 3.36) - (0.43, 2.37)
P-value 0.439 0.409 0.979
(95% CI) (0.67, 2.51) - (0.62, 3.23) - (0.43, 2.35)
P-value 0.447 0.412 0.994
Time to first event
(95% CI) (0.53, 1.44) - (0.46, 1.58) - (0.39, 2.16) -
P-value 0.598 0.621 0.840
(95% CI) (0.53, 1.44) - (0.46, 1.58) - (0.39, 2.14) -
P-value 0.589 0.616 0.827
*Resulted in death
Table S10.7 Grade 3 or above clinical and laboratory adverse events to week 96
Total A B
Person years 635 634 1269 279 273 552 357 361 718
Number of events [Number of young 87 [60] 111 [76] 198 [136] 59 [39] 52 [35] 111 [74] 28 [21] 59 [41] 87 [62]
people]
Biochemical 13 [13] 44 [32] 57 [45] 7 [7] 7 [7] 14 [14] 6 [6] 37 [25] 43 [31]
Hypocalcaemia - asymptomatic 1 [1] 4 [4] 5 [5] 1 [1] 1 [1] 2 [2] 0 [0] 3 [3] 3 [3]
Hypophosphataemia 1 [1] 1 [1] 2 [2] 1 [1] 0 [0] 1 [1] 0 [0] 1 [1] 1 [1]
Proteinuria 2 [2] 0 [0] 2 [2] 0 [0] 0 [0] 0 [0] 2 [2] 0 [0] 2 [2]
Raised ALT 1 [1] 1 [1] 2 [2] 1 [1] 1 [1] 2 [2] 0 [0] 0 [0] 0 [0]
Raised AST 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Raised LDL 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Raised liver enzymes 2 [2] 1 [1] 3 [3] 0 [0] 1 [1] 1 [1] 2 [2] 0 [0] 2 [2]
raised low density lipoprotein 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Cardiovascular 3 [3] 0 [0] 3 [3] 3 [3] 0 [0] 3 [3] 0 [0] 0 [0] 0 [0]
Hypertension 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
88
Eye 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Uveitis 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Haematological 29 [25] 22 [20] 51 [45] 17 [16] 13 [13] 30 [29] 12 [9] 9 [7] 21 [16]
Anaemia with no clinical symptoms 7 [7] 5 [4] 12 [11] 5 [5] 3 [3] 8 [8] 2 [2] 2 [1] 4 [3]
Low lymphocytes 1 [1] 1 [1] 2 [2] 1 [1] 1 [1] 2 [2] 0 [0] 0 [0] 0 [0]
Neutropenia 10 [8] 7 [7] 17 [15] 7 [6] 5 [5] 12 [11] 3 [2] 2 [2] 5 [4]
Thrombocytopenia 7 [6] 7 [7] 14 [13] 1 [1] 3 [3] 4 [4] 6 [5] 4 [4] 10 [9]
Hepatic 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Acute sinusitis 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
Appendicitis 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Candidiasis of oesophagus, trachea, 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
bronchi or lungs
Chest infection 1 [1] 1 [1] 2 [2] 1 [1] 0 [0] 1 [1] 0 [0] 1 [1] 1 [1]
Hepatitis A 2 [2] 0 [0] 2 [2] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1]
Herpes Zoster (Varicella Zoster) - 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
cutaneous
Measles 1 [1] 1 [1] 2 [2] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1] 2 [2]
Oral candida 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Pneumonia - other bacterial * 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Pneumonia - other organism (not 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0] 0 [0] 1 [1] 1 [1]
bacterial)
organism
Presumed septicaemia/bacteremia - not 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
investigated *
Septic arthritis 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Skin abscess 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
89
negative or not done

Pneumothorax 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Bone fracture 2 [2] 0 [0] 2 [2] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1]
Nervous System 5 [5] 1 [1] 6 [6] 3 [3] 1 [1] 4 [4] 2 [2] 0 [0] 2 [2]
Headache 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Traumatic 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Oral 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Mouth ulcers 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
incomplete)
Psychiatric 3 [3] 2 [2] 5 [5] 2 [2] 1 [1] 3 [3] 1 [1] 1 [1] 2 [2]
Psychosis, mania 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Renal 2 [2] 0 [0] 2 [2] 2 [2] 0 [0] 2 [2] 0 [0] 0 [0] 0 [0]
Skin 1 [1] 1 [1] 2 [2] 0 [0] 1 [1] 1 [1] 1 [1] 0 [0] 1 [1]
Burns 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0] 1 [1] 0 [0] 1 [1]
Systemic 1 [1] 1 [1] 2 [2] 1 [1] 1 [1] 2 [2] 0 [0] 0 [0] 0 [0]
Kwashiorkor 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Wasting syndrome uninvestigated 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Tumours 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Other 0 [0] 2 [2] 2 [2] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1]
Non-fatal trauma 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Clinical (or labs reported by site) events 69 (100%) 77 (100%) 146 (100%) 46 (100%) 40 (100%) 86 (100%) 23 (100%) 37 (100%) 60 (100%)
reviewed by ERC
Events identified from routine labs (Not 18 (21%) 34 (31%) 52 (26%) 13 (22%) 12 (23%) 25 (23%) 5 (18%) 22 (37%) 27 (31%)
ERCd), N (% of total events)
Asymtomatic lab events, N (% of total 34 (39%) 54 (49%) 88 (44%) 20 (34%) 17 (33%) 37 (33%) 14 (50%) 37 (63%) 51 (59%)
events)
(95% CI) (11.1, 16.9) (14.5, 21.1) (13.6, 17.9) (16.4, 27.3) (14.5, 25.0) (16.7, 24.2) (5.4, 11.4) (12.7, 21.1) (9.8, 15.0)
(95% CI) (0.54, 1.12) - (0.68, 1.83) - (0.28, 0.83) -
P-value 0.178 0.676 0.009
90
(95% CI) (0.54, 1.12) - (0.68, 1.83) - (0.28, 0.83) -

P-value 0.179 0.665 0.009
Time to first event
(95% CI) (0.55, 1.09) - (0.71, 1.77) - (0.29, 0.83) -
P-value 0.145 0.619 0.007
(95% CI) (0.55, 1.09) - (0.71, 1.78) - (0.28, 0.81) -
P-value 0.140 0.606 0.006
*Resulted in death
Table S10.8 Adverse events leading to ART modification (any grade) to week 96
Total A B
Person years 635 634 1269 279 273 552 357 361 718
Number of events [Number of young people+] 6 [5] 15 [15] 21 [20] 4 [3] 7 [7] 11 [10] 2 [2] 8 [8] 10 [10]
Biochemical 0 [0] 4 [4] 4 [4] 0 [0] 0 [0] 0 [0] 0 [0] 4 [4] 4 [4]
Haematological 1 [1] 3 [3] 4 [4] 0 [0] 0 [0] 0 [0] 1 [1] 3 [3] 4 [4]
Neutropenia 0 [0] 2 [2] 2 [2] 0 [0] 0 [0] 0 [0] 0 [0] 2 [2] 2 [2]
Hepatitis A 2 [2] 0 [0] 2 [2] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1]
Nervous System 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Dizziness^ 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
Psychiatric 2 [2] 1 [1] 3 [3] 2 [2] 1 [1] 3 [3] 0 [0] 0 [0] 0 [0]
Depression 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Psychosis, mania 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 0 [0] 0 [0] 0 [0]
Skin 0 [0] 3 [3] 3 [3] 0 [0] 3 [3] 3 [3] 0 [0] 0 [0] 0 [0]
Gynaecomastia 0 [0] 1 [1] 1 [1] 0 [0] 1 [1] 1 [1] 0 [0] 0 [0] 0 [0]
91

(95% CI) (0.4, 2.1) (1.4, 3.9) (1.1, 2.5) (0.5, 3.8) (1.2, 5.4) (1.1, 3.6) (0.1, 2.2) (1.1, 4.4) (0.7, 2.6)
Rate ratio* 0.40 1 (ref) 0.56 1 (ref) 0.25 1 (ref)
(95% CI) (0.14, 1.13) - (0.14, 2.26) - (0.05, 1.18) -
P-value 0.083 0.415 0.080
Adj. Rate ratio** 0.39 1 (ref) 0.54 1 (ref) 0.26 1 (ref)
(95% CI) (0.14, 1.10) - (0.14, 2.13) - (0.06, 1.20) -
P-value 0.076 0.379 0.083
Time to first event
Hazard ratio* 0.33 1 (ref) 0.42 1 (ref) 0.25 1 (ref)
(95% CI) (0.12, 0.91) - (0.11, 1.63) - (0.05, 1.18) -
P-value 0.032 0.210 0.080
Adj. hazard ratio** 0.33 1 (ref) 0.41 1 (ref) 0.25 1 (ref)
(95% CI) (0.12, 0.90) - (0.10, 1.57) - (0.05, 1.19) -
P-value 0.030 0.191 0.082
+One participant (DTG) switched ART on two occasions, the first was due to a hypersensitivity reaction and then switched again due to depression.
*Adjusted for ODYSSEY A and B strata in total. Unadjusted in A and B comparison.
**Adjusted for all stratification factors.
^One participant had a decrease in EFV due to dizziness, however, given that this is not a change in drug, this participant is categorised as remaining on their strict initial regimen in the
table summarising ART substitutions.
92
S 11 Patient reported outcomes

Table S11.1 -up
Total A B
Total number of 333 334 667 147 146 293 186 188 374
participants*
Number of participants 7 (2.1%) 2 (0.6%) 9 (1.3%) 5 (3.4%) 1 (0.7%) 6 (2.0%) 2 (1.1%) 1 (0.5%) 3 (0.8%)
reporting any+ issue with
mobility during follow-up (%)
selfcare during follow-up (%)
activities during follow-up
(%)
pain during follow-up (%)
anxiety during follow-up (%)
*Total number of participants contributing to QoL analysis (at least one questionnaire completed during follow-up whilst >=8y/o)
+The EQ5D- -care, usual activities, pain/discomfort, and anxiety/depression. Each question has
three dimensions: no problems, some problems, and extreme problems. This analysis reports whether the participant reports any problems (some or extreme). Percentages are of
participants completing at least one EQ5D-3L questionnaire during follow-up.
Table S11.2 Summary of carer/self-reported adherence

Total A B
Participants randomised 350 357 707 154 157 311 196 200 396
Dose missed in the last week*
Week 0 10 ( 6%) 15 ( 9%) 25 ( 8%) 0 ( 0%) 0 ( 0%) 0 ( 0%) 10 ( 6%) 15 ( 9%) 25 ( 8%)
Week 4 17 ( 6%) 21 ( 7%) 38 ( 7%) 5 ( 4%) 10 ( 8%) 15 ( 6%) 12 ( 7%) 11 ( 7%) 23 ( 7%)
Week 12 23 ( 8%) 23 ( 8%) 46 ( 8%) 8 ( 6%) 12 (10%) 20 ( 8%) 15 ( 9%) 11 ( 7%) 26 ( 8%)
93
Week 24 34 (10%) 33 (10%) 67 (10%) 8 ( 6%) 12 ( 8%) 20 ( 7%) 26 (14%) 21 (11%) 47 (13%)
Week 36 37 (11%) 31 ( 9%) 68 (10%) 14 (10%) 14 ( 9%) 28 (10%) 23 (12%) 17 ( 9%) 40 (10%)
Week 48 27 ( 8%) 34 (10%) 61 ( 9%) 12 ( 8%) 12 ( 8%) 24 ( 8%) 15 ( 8%) 22 (11%) 37 (10%)
Week 60 33 (10%) 32 (10%) 65 (10%) 11 ( 8%) 13 ( 9%) 24 ( 8%) 22 (12%) 19 (10%) 41 (11%)
Week 72 34 (10%) 36 (11%) 70 (10%) 12 ( 8%) 16 (11%) 28 (10%) 22 (11%) 20 (10%) 42 (11%)
Week 84 36 (11%) 32 (10%) 68 (10%) 16 (11%) 16 (11%) 32 (11%) 20 (10%) 16 ( 8%) 36 ( 9%)
Week 96 34 (10%) 39 (12%) 73 (11%) 15 (10%) 18 (13%) 33 (12%) 19 (10%) 21 (11%) 40 (11%)
Week 108 27 ( 9%) 34 (11%) 61 (10%) 12 ( 9%) 14 (12%) 26 (10%) 15 ( 8%) 20 (11%) 35 ( 9%)
Week 120 23 ( 8%) 22 ( 9%) 45 ( 8%) 11 ( 9%) 7 ( 6%) 18 ( 8%) 12 ( 8%) 15 (10%) 27 ( 9%)
Week 132 20 ( 9%) 20 ( 9%) 40 ( 9%) 11 (10%) 8 ( 8%) 19 ( 9%) 9 ( 7%) 12 (10%) 21 ( 9%)
Week 144 9 ( 6%) 14 ( 9%) 23 ( 7%) 5 ( 6%) 5 ( 6%) 10 ( 6%) 4 ( 5%) 9 (13%) 13 ( 9%)
Week 156 4 ( 4%) 3 ( 3%) 7 ( 4%) 0 ( 0%) 1 ( 2%) 1 ( 1%) 4 ( 8%) 2 ( 5%) 6 ( 7%)
Week 168 1 ( 2%) 6 (12%) 7 ( 7%) 1 ( 3%) 4 (14%) 5 ( 9%) 0 ( 0%) 2 (10%) 2 ( 5%)
Week 180 2 (15%) 0 ( 0%) 2 ( 8%) 2 (20%) 0 ( 0%) 2 (11%) 0 ( 0%) 0 ( 0%) 0 ( 0%)
Total # of reports of dose missed 361 ( 9%) 380 (10%) 741 ( 9%) 143 ( 8%) 162 ( 9%) 305 ( 9%) 218 (10%) 218 (10%) 436 (10%)
in last week over follow-up (% of
all follow-up questionnaires)
# of participants reporting dose 96 (28%) 93 (26%) 189 (27%) 34 (22%) 39 (25%) 73 (24%) 62 (32%) 54 (27%) 116 (29%)
missed in last week at follow-
up visit
*Dose reported as missed in last week by carer or participant or both. Two versions of the questionnaires were used (version 1 between 21st September 2016 and 15th January 2019,
version 2 between 6th April 2017 and 24th April 2020; version 2 was introduced with protocol version 3.0 with the date of implementation varying between sites). In version 1, the question
our child missed any antiretroviral medicines? (Tick one answer only) within the last week, 1-2 weeks ago, 2-4 weeks ago, 1-3 months ago, or missed
nothing within the last 3 months and in version 2 he last week? yes or no version 1) and
version 2) have been combined as indicating a dose reported as missed in last week.
Table S11.3 Summary of carer/self-reported acceptability of treatment during follow-up

Total A B
Problems with taste/does not like taste*
Week 4 29 (10%) 40 (14%) 69 (12%) 16 (13%) 28 (24%) 44 (19%) 13 ( 8%) 12 ( 7%) 25 ( 8%)
Week 12 16 ( 8%) 22 (11%) 38 (10%) 7 ( 9%) 14 (19%) 21 (14%) 9 ( 8%) 8 ( 7%) 17 ( 7%)
Week 24 20 ( 6%) 24 ( 7%) 44 ( 7%) 14 (10%) 16 (12%) 30 (11%) 6 ( 3%) 8 ( 4%) 14 ( 4%)
Week 48 22 ( 7%) 41 (12%) 63 ( 9%) 13 ( 9%) 27 (19%) 40 (14%) 9 ( 5%) 14 ( 7%) 23 ( 6%)
Week 72 22 ( 7%) 28 ( 8%) 50 ( 7%) 10 ( 7%) 16 (11%) 26 ( 9%) 12 ( 6%) 12 ( 6%) 24 ( 6%)
94
Week 96 16 ( 5%) 23 ( 7%) 39 ( 6%) 10 ( 7%) 13 ( 9%) 23 ( 8%) 6 ( 3%) 10 ( 5%) 16 ( 4%)
Week 120 8 ( 3%) 18 ( 7%) 26 ( 5%) 4 ( 4%) 10 ( 9%) 14 ( 6%) 4 ( 3%) 8 ( 5%) 12 ( 4%)
Week 144 8 ( 5%) 10 ( 7%) 18 ( 6%) 6 ( 7%) 8 (10%) 14 ( 9%) 2 ( 3%) 2 ( 3%) 4 ( 3%)
Week 168 3 ( 6%) 3 ( 7%) 6 ( 6%) 1 ( 4%) 2 ( 7%) 3 ( 5%) 2 ( 9%) 1 ( 6%) 3 ( 8%)
Total # of reports of problems over follow-up (% of 144 ( 6%) 209 ( 9%) 353 ( 8%) 81 ( 8%) 134 (14%) 215 (11%) 63 ( 5%) 75 ( 6%) 138 ( 5%)
# of participants reporting problems at follow-up 30 ( 9%) 47 (13%) 77 (11%) 18 (12%) 30 (19%) 48 (16%) 12 ( 6%) 17 ( 9%) 29 ( 7%)
visit
Problems with swallowing/not easy to swallow~
Week 4 18 ( 6%) 44 (16%) 62 (11%) 7 ( 6%) 20 (17%) 27 (11%) 11 ( 7%) 24 (15%) 35 (11%)
Week 12 9 ( 5%) 14 ( 7%) 23 ( 6%) 6 ( 8%) 8 (11%) 14 ( 9%) 3 ( 3%) 6 ( 5%) 9 ( 4%)
Week 24 13 ( 4%) 17 ( 5%) 30 ( 5%) 6 ( 4%) 8 ( 6%) 14 ( 5%) 7 ( 4%) 9 ( 5%) 16 ( 4%)
Week 48 14 ( 4%) 18 ( 5%) 32 ( 5%) 10 ( 7%) 10 ( 7%) 20 ( 7%) 4 ( 2%) 8 ( 4%) 12 ( 3%)
Week 72 13 ( 4%) 16 ( 5%) 29 ( 4%) 7 ( 5%) 8 ( 6%) 15 ( 5%) 6 ( 3%) 8 ( 4%) 14 ( 4%)
Week 96 10 ( 3%) 14 ( 4%) 24 ( 4%) 7 ( 5%) 7 ( 5%) 14 ( 5%) 3 ( 2%) 7 ( 4%) 10 ( 3%)
Week 120 6 ( 2%) 8 ( 3%) 14 ( 3%) 2 ( 2%) 5 ( 5%) 7 ( 3%) 4 ( 3%) 3 ( 2%) 7 ( 2%)
Week 144 2 ( 1%) 11 ( 7%) 13 ( 4%) 2 ( 2%) 9 (11%) 11 ( 7%) 0 ( 0%) 2 ( 3%) 2 ( 1%)
Week 168 1 ( 2%) 3 ( 7%) 4 ( 4%) 1 ( 4%) 2 ( 7%) 3 ( 5%) 0 ( 0%) 1 ( 6%) 1 ( 3%)
Total # of reports of problems over follow-up (% of 86 ( 4%) 145 ( 6%) 231 ( 5%) 48 ( 5%) 77 ( 8%) 125 ( 6%) 38 ( 3%) 68 ( 5%) 106 ( 4%)
# of participants reporting problems at follow-up 13 ( 4%) 29 ( 8%) 42 ( 6%) 9 ( 6%) 15 (10%) 24 ( 8%) 4 ( 2%) 14 ( 7%) 18 ( 5%)
visit
*Problems with taste/does not like taste as reported by carer or participant or both. Two versions of the questionnaires were used (version 1 between 18th October 2016 and 27th
December 2018, version 2 between 19th April 2017 and 24th April 2020; version 2 was introduced with protocol version 3.0 with the date of implementation varying between sites). In
version 1 version 2
version 1 version 2) have been combined as indicating problems with taste/does not like taste.
~ Problems swallowing/not easy to swallow as reported by carer or participant or both. Two versions of the questionnaires were used (version 1 between 18th October 2016 and 27th
December 2018, version 2 between 19th April 2017 and 24th April 2020; version 2 was introduced with protocol version 3.0 with the date of implementation varying between sites). In
version 1 version 2 yes or no
version 1 version 2) have been combined as indicating difficulty swallowing/not easy to swallow.
95
S 12 Antiretroviral therapy
Table S12.1 Summary of initial ART regimens
Total A B
NRTI backbone
ABC 3TC 232 (66%) 231 (65%) 463 (65%) 126 (82%) 122 (78%) 248 (80%) 106 (54%) 109 (55%) 215 (54%)
ZDV 3TC 37 (11%) 40 (11%) 77 (11%) 0 ( 0%) 3 ( 2%) 3 ( 1%) 37 (19%) 37 (19%) 74 (19%)
TDF/TAF* + 3TC/FTC 80 (23%) 84 (24%) 164 (23%) 28 (18%) 32 (20%) 60 (19%) 52 (27%) 52 (26%) 104 (26%)
ABC TDF 1 ( 0%) 2 ( 1%) 3 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0%) 1 ( 1%) 2 ( 1%) 3 ( 1%)
Third agent drug class
INSTI 350 (100%) 1 ( 0%) 351 (50%) 154 (100%) 1 ( 1%) 155 (50%) 196 (100%) 0 ( 0%) 196 (49%)
NNRTI 0 ( 0%) 154 (43%) 154 (22%) 0 ( 0%) 149 (95%) 149 (48%) 0 ( 0%) 5 ( 3%) 5 ( 1%)
PI 0 ( 0%) 202 (57%) 202 (29%) 0 ( 0%) 7 ( 4%) 7 ( 2%) 0 ( 0%) 195 (98%) 195 (49%)
Third agent
ATV 0 ( 0%) 49 (14%) 49 ( 7%) 0 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0%) 49 (25%) 49 (12%)
DRV 0 ( 0%) 6 ( 2%) 6 ( 1%) 0 ( 0%) 4 ( 3%) 4 ( 1%) 0 ( 0%) 2 ( 1%) 2 ( 1%)
DTG 350 (100%) 0 ( 0%) 350 (50%) 154 (100%) 0 ( 0%) 154 (50%) 196 (100%) 0 ( 0%) 196 (49%)
EFV 0 ( 0%) 150 (42%) 150 (21%) 0 ( 0%) 145 (92%) 145 (47%) 0 ( 0%) 5 ( 3%) 5 ( 1%)
EVG 0 ( 0%) 1 ( 0%) 1 ( 0%) 0 ( 0%) 1 ( 1%) 1 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0%)
LOP 0 ( 0%) 147 (41%) 147 (21%) 0 ( 0%) 3 ( 2%) 3 ( 1%) 0 ( 0%) 144 (72%) 144 (36%)
NVP 0 ( 0%) 2 ( 1%) 2 ( 0%) 0 ( 0%) 2 ( 1%) 2 ( 1%) 0 ( 0%) 0 ( 0%) 0 ( 0%)
RLP 0 ( 0%) 2 ( 1%) 2 ( 0%) 0 ( 0%) 2 ( 1%) 2 ( 1%) 0 ( 0%) 0 ( 0%) 0 ( 0%)
* 2 participants on SOC initiated TAF + FTC (1 ODYSSEY A, 1 ODYSSEY B).
Table S12.2 Summary of substitutions and changes to initial ART regimens (to trial censoring date)
Total A B
ODYSSEY regimen at last visit,
number of participants (%):
1st:strict initial 327 (93%) 297 (83%) 624 (88%) 146 (95%) 121 (77%) 267 (86%) 181 (92%) 176 (88%) 357 (90%)
1st:NRTI substitution/reduction 6 ( 2%) 11 ( 3%) 17 ( 2%) 1 ( 1%) 5 ( 3%) 6 ( 2%) 5 ( 3%) 6 ( 3%) 11 ( 3%)
1st:substitution 3rd agent 2~ ( 1%) 13 ( 4%) 15 ( 2%) 2 ( 1%) 6 ( 4%) 8 ( 3%) 0 ( 0%) 7 ( 4%) 7 ( 2%)
2nd regimen 8 ( 2%) 31 ( 9%) 39 ( 6%) 1 ( 1%) 22 (14%) 23 ( 7%) 7 ( 4%) 9 ( 5%) 16 ( 4%)
3rd regimen* 5 ( 1%) 1 ( 0%) 6 ( 1%) 3 ( 2%) 1 ( 1%) 4 ( 1%) 2 ( 1%) 0 ( 0%) 2 ( 1%)
96
Stopped** 2 ( 1%) 4 ( 1%) 6 ( 1%) 1 ( 1%) 2 ( 1%) 3 ( 1%) 1 ( 1%) 2 ( 1%) 3 ( 1%)
Changes to 3rd agent
Number of participants changing 3rd 15 ( 4%) 46 (13%) 61 ( 9%) 6 ( 4%) 29 (18%) 35 (11%) 9 ( 5%) 17 ( 9%) 26 ( 7%)
agent
Number of changes to 3rd agent 21 52 73 10 34 44 11 18 29
Reason for change
Treatment failure 2 22 24 1 18 19 1 4 5
Toxicity 5 12 17# 4 6 10 1 6 7
Pregnancy 7 0 7 1 0 1 6 0 6
Simplification 0 11 11 0 5 5 0 6 6
Other*** 7 7 14 4 5 9 3 2 5
Changes to NRTI backbone
Number of participants changing 10 ( 3%) 36 (10%) 46 ( 7%) 4 ( 3%) 25 (16%) 29 ( 9%) 6 ( 3%) 11 ( 6%) 17 ( 4%)
NRTI backbone
Number of changes to NRTI 14 50 64 8 34 42 6 16 22
backbone
Reason for change
Treatment failure 2 19 21¥ 1 14 15 1 5 6
Toxicity 4 11 15 2 5 7 2 6 8
Other 7 9 16 5 6 11 2 3 5
~Two participants within DTG arm switched third agent but remained on first regimen: (1) Switched from ABC 3TC DTG to TDF FTC EFV at hospital admission due to incorrect prescribing,
and continued to take incorrect combinations of the two regimens for ~5 weeks. After counselling, they returned to their initial regimen but were no longer defined as being on strict initial
regimen. (2) Participant switched from ABC 3TC DTG to ABC 3TC EFV to withdraw from the trial due to transport issues and return to standard clinical practice.
¥Five participants in SOC switched their 3rd agent for treatment failure but did not switch their NRTI backbone: (1) switched from ABC 3TC EFV to ABC 3TC LOP; (2) switched from TDF
FTC EFV to TDF FTC LOP; (3) switched from ABC 3TC EFV to ABC 3TC LOP; (4) switched from ABC 3TC EFV to ABC 3TC DTG; and (5) switched from ABC 3TC LOP to ABC 3TC ATV.
*Five participants in DTG arm were on their 3rd regimen by the end of follow-up: (1) switched to a 2nd regimen due to toxicity, and then switched to a 3rd regimen due to new toxicity; (2)
switched to a 2nd regimen due to toxicity and then a 3rd due to treatment failure; (3) and (4) switched off DTG due to pregnancy and then returned to previous regimen when no longer
pregnant; (5) switched to SOC accidentally by the site, and was then switched back to initial regimen after discussion with the MRC CTU. One participant in SOC was on a 3rd regimen by
the end of follow-up: switched to a 2nd regimen due to toxicity and then to 3rd due to treatment failure.
**Two participants in the DTG arm had stopped ART at their last visit: both remained in follow-up but stopped 3 weeks (at week 123) and 4 weeks (at week 171, respectively) prior to trial
censoring date. Four participants in the SOC arm had stopped ART at their latest visit: (1) and (2) remained in follow-up but had stopped ART one month (at week 123) and 10 days (at
week 133, respectively) prior to trial censoring date (latter switched 3rd agent due to toxicity at week 4); (3) switched NRTI backbone due to adverse event at week 20 and then stopped
ART at week 30 due to a terminal illness (died at week 30, 78 weeks prior to trial censoring date); (4) stopped ART at week 34 and subsequently withdrew at week 44.
1) and (2) switched from EFV and ATV (respectively) back to DTG (defined as third regimen) when no
longer pregnant at week 120 and 114, respectively; (3) switched their 3rd agent twice because their regimen was switched from DTG to SOC accidentally by the site, and was then
97
switched back to DTG after discussion with the MRC CTU (week 8 and 10); (4) 3rd agent was switched twice because the participant was incorrectly prescribed when admitted to hospital,
they were subsequently switched back to the correct 3rd agent (week 2 and 3); (5) switched off DTG to EFV to return to SOC upon withdrawing from the study (week 12). There were seven
cation at week 131; (2) switched from ATV to DTG at week
131 due to national guidelines; (3) switched from ATV to DTG at week 133 due to patient/carer decision; (4) switched from LOP to EFV due to incorrect prescribing at week 2; (5) switched
from EFV to EVG due to a patient/carer decision to switch site at week 90; (6) added DTG to their regimen at week 99 (an additional 3rd agent with LOP) due to a mix up of drugs at home
but subsequently stopped DTG; (7) switched from EFV to DTG at week 25 due to a clinical decision based on non-compliance.
#One participant switched from ATV to LOP due to raised bilirubin, and then subsequently switched back to ATV for simplification 2.5 months later. The ERC said that neither of the raised
bilirubin events they reviewed were ART modifying and therefore corresponding ART-modifying events do not appear in ART modification table (S10.4).
Table S12.3 Summary of substitutions and changes to initial ART regimens (to week 96)
Total A B
ODYSSEY regimen at last visit,
number of participants (%):
1st:strict initial 333 (95%) 316 (89%) 649 (92%) 147 (95%) 131 (83%) 278 (89%) 186 (95%) 185 (93%) 371 (94%)
1st:NRTI substitution/reduction 4 ( 1%) 7 ( 2%) 11 ( 2%) 0 ( 0%) 3 ( 2%) 3 ( 1%) 4 ( 2%) 4 ( 2%) 8 ( 2%)
1st:substitution 3rd agent 2~ ( 1%) 8 ( 2%) 10 ( 1%) 2 ( 1%) 4 ( 3%) 6 ( 2%) 0 ( 0%) 4 ( 2%) 4 ( 1%)
2nd regimen 8 ( 2%) 22 ( 6%) 30 ( 4%) 3 ( 2%) 16 (10%) 19 ( 6%) 5 ( 3%) 6 ( 3%) 11 ( 3%)
3rd regimen* 2 ( 1%) 1 ( 0%) 3 ( 0%) 1 ( 1%) 1 ( 1%) 2 ( 1%) 1 ( 1%) 0 ( 0%) 1 ( 0%)
Stopped** 1 ( 0%) 3 ( 1%) 4 ( 1%) 1 ( 1%) 2 ( 1%) 3 ( 1%) 0 ( 0%) 1 ( 1%) 1 ( 0%)
Changes to 3rd agent
Number of participants changing 3rd 12 ( 3%) 31 ( 9%) 43 ( 6%) 6 ( 4%) 21 (13%) 27 ( 9%) 6 ( 3%) 10 ( 5%) 16 ( 4%)
agent
Number of changes to 3rd agent 15 33 48 8 23 31 7 10 17
Reason for change
Treatment failure 1 14 15 0 13 13 1 1 2
Toxicity 5 10 15 4 5 9 1 5 6
Pregnancy 4 0 4 1 0 1 3 0 3
Other*** 5 3 8 3 3 6 2 0 2
Changes to NRTI backbone
Number of participants changing 7 ( 2%) 22 ( 6%) 29 ( 4%) 2 ( 1%) 17 (11%) 19 ( 6%) 5 ( 3%) 5 ( 3%) 10 ( 3%)
NRTI backbone
Number of changes to NRTI 11 29 40 6 22 28 5 7 12
backbone
Reason for change
Treatment failure 1 12 13¥ 0 10 10 1 2 3
98
Toxicity 4 9 13 2 5 7 2 4 6
Other 5 4 9 4 4 8 1 0 1
~Two participants within DTG arm switched third agent but remained on first regimen: (1) Switched from ABC 3TC DTG to TDF FTC EFV at hospital admission due to incorrect prescribing,
and continued to take incorrect combinations of the two regimens for ~5 weeks. After counselling, they returned to their initial regimen but were no longer defined as being on strict initial
regimen. (2) Participant switched from ABC 3TC DTG to ABC 3TC EFV to withdraw from the trial due to transport issues and return to standard clinical practice.
¥Three participants in SOC switched their 3rd agent for treatment failure but did not switch their NRTI backbone: (1) switched from ABC 3TC EFV to ABC 3TC LOP; (2) switched from TDF
FTC EFV to TDF FTC LOP; (3) switched from ABC 3TC EFV to ABC 3TC LOP.
*Two participants in DTG arm were on their 3rd regimen by the end of follow-up: (1) switched to a 2nd regimen due to toxicity, and then switched to a 3rd regimen due to new toxicity; (2)
switched to SOC accidentally by the site and was then switched back to initial regimen after discussion with the MRC CTU. One participant in SOC was on a 3rd regimen by the end of
follow-up: switched to a 2nd regimen due to toxicity and then to 3rd due to treatment failure.
**One participant in the DTG arm had stopped ART at their latest visit prior to week 96: participant reported not taking their ART in the 5 weeks prior to week 96 visit, which was 2 days after
scheduled week 96 visit, and were therefore defined as being off ART at this timepoint. Participant re-initiated ART at week 96 visit and remained in follow-up beyond trial censoring date.
Three participants in the SOC arm had stopped ART at their latest visit prior to week 96: (1) switched NRTI backbone due to adverse event at week 20 and then stopped ART at week 30
due to a terminal illness (died at week 30); (2) stopped ART at week 84, re-starting ART at week 97 (subsequently withdrew at week 109); (3) stopped ART at week 34 and subsequently
withdrew at week 44.
***There were five 1) switched their 3rd agent twice because their regimen was switched from DTG to SOC accidentally by the
site, and was then switched back to DTG after discussion with the MRC CTU (week 8 and 10); (2) 3rd agent was switched twice because the participant was incorrectly prescribed when
admitted to hospital, they were subsequently switched back to the correct 3rd agent (week 2 and 3); (3) switched off DTG to EFV to return to SOC upon withdrawing from the study (week
12). There were three 1) switched from LOP to EFV due to incorrect prescribing at week 2; (2) switched from EFV to EVG due to a
patient/carer decision to switch site at week 90; (3) switched from EFV to DTG at week 25 due to a clinical decision based on non-compliance.
99
S 13 Safety data by DTG dose

Table S13.1 Summary of adverse events frequency and rates by DTG dose
ART regimen* SAEs Grade 3 or above ART Modifying Events
Follow-up Time** (years) N Rate p.100PYs N Rate p.100PYs N Rate p.100PYs
[N Children] [95% CI] [N Children] [95% CI] [N Children] [95% CI]
DTG regimen: lower DTG dose 176.85 26 14.70 39 22.05 2 1.13
[15] [9.60-21.54] [26] [15.68-30.15] [2] [0.14-4.09]
DTG regimen: higher DTG dose 292.51 16 5.47 27 9.23 2 0.68
[8] [3.13-8.88] [21] [6.08-13.43] [2] [0.08-2.47]
SOC regimen: <40kg 521.19 27 5.18 71 13.62 6 1.15
[24] [3.41-7.54] [51] [10.64-17.18] [6] [0.42-2.51]
DTG regimen: 40kg+ 453.12 16 3.53 36 7.94 1 0.22
[12] [2.02-5.73] [27] [5.56-11.00] [1] [0.01-1.23]
SOC regimen: 40kg+ 397.39 15 3.77 59 14.85 9 2.26
[14] [2.11-6.23] [38] [11.30-19.15] [9] [1.04-4.30]
*Lower DTG doses: the trial opened with children on doses evaluated by the IMPAACT dose-finding study and/or approved by FDA and/or EMA (20mg film-coated tablets (FCTs) in weight-
band 15<20kg, 25mg in 20-<30kg and 35mg in 30-<40kg). Nested PK sub studies were performed within ODYSSEY to evaluate simplified dosing using WHO weight bands, and
subsequently to evaluate dosing with dispersible DTG (which has higher bioavailability than film-coated tablets). Following sub-study results, children outside of the PK sub studies then
also moved to higher DTG doses: 25mg DT in 14-<25kg, 50mg FCT
Where DTG dose was given BID due to co-administration with rifampicin, follow-up and events are included within the respective QD group.
**Children contribute to follow-up whilst on a protocol-defined DTG dose in DTG arm or a SOC regimen with a non-DTG containing third agent in SOC arm. Follow-up and adverse events
occurring whilst off these regimens do not contribute to this analysis (34.1 person-years; 9 SAEs, 13 grade >=3 AEs, 3 ART-modifying AE)
Reference: Moore, C.L., Turkova, A., Mujuru, H. et al. ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral
therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing. BMC Infect Dis 21, 5 (2021).
https://doi.org/10.1186/s12879-020-05672-6
100
S 14 Anthropometric measures
data at baseline.
Table S14.1 Total population - Height (cm) change over follow-up

12 345 1.2 (0.1) 350 1.0 (0.1) 0.2 (0.1) [-0.1, 0.4] 0.2 (0.1) [-0.1, 0.4]
24 344 2.2 (0.1) 347 2.0 (0.1) 0.2 (0.1) [-0.1, 0.5] 0.2 (0.1) [-0.1, 0.5]
36 342 3.4 (0.1) 344 3.0 (0.1) 0.3 (0.2) [0.0, 0.6] 0.3 (0.2) [0.0, 0.6]
48 342 4.6 (0.1) 340 4.1 (0.1) 0.5 (0.2) [0.1, 0.8] 0.5 (0.2) [0.1, 0.8]
60 341 5.6 (0.2) 334 5.1 (0.2) 0.5 (0.2) [0.1, 0.9] 0.5 (0.2) [0.1, 0.9]
72 337 6.7 (0.2) 334 6.1 (0.2) 0.5 (0.2) [0.1, 1.0] 0.5 (0.2) [0.1, 1.0]
84 332 7.8 (0.2) 333 7.0 (0.2) 0.8 (0.3) [0.2, 1.3] 0.8 (0.3) [0.2, 1.3]
96 330 8.8 (0.2) 329 7.9 (0.2) 0.8 (0.3) [0.2, 1.4] 0.8 (0.3) [0.2, 1.4]
108 304 9.7 (0.2) 305 8.8 (0.2) 0.9 (0.3) [0.2, 1.6] 0.9 (0.3) [0.2, 1.6]
120 261 10.7 (0.3) 252 9.5 (0.3) 1.1 (0.4) [0.3, 1.9] 1.2 (0.4) [0.4, 2.0]
132 215 11.8 (0.3) 213 10.6 (0.3) 1.2 (0.5) [0.2, 2.1] 1.2 (0.5) [0.2, 2.1]
144 149 12.1 (0.4) 148 11.8 (0.4) 0.2 (0.6) [-0.9, 1.4] 0.3 (0.6) [-0.8, 1.4]
156 87 13.2 (0.5) 89 12.3 (0.5) 1.0 (0.7) [-0.5, 2.4] 1.0 (0.7) [-0.4, 2.5]
168 41 13.1 (0.8) 39 12.7 (0.9) 0.4 (1.1) [-1.9, 2.7] 0.9 (1.2) [-1.6, 3.3]
Table S14.2 ODYSSEY A - Height (cm) change over follow-up

12 150 1.0 (0.1) 152 0.8 (0.1) 0.2 (0.2) [-0.2, 0.6] 0.2 (0.2) [-0.2, 0.6]
24 149 2.2 (0.2) 149 1.9 (0.2) 0.3 (0.2) [-0.1, 0.7] 0.3 (0.2) [-0.2, 0.7]
36 149 3.4 (0.2) 148 3.0 (0.2) 0.4 (0.2) [-0.1, 0.9] 0.4 (0.2) [-0.1, 0.9]
48 149 4.6 (0.2) 145 4.0 (0.2) 0.6 (0.3) [0.1, 1.2] 0.7 (0.3) [0.1, 1.2]
60 148 5.7 (0.2) 141 4.9 (0.2) 0.7 (0.3) [0.1, 1.4] 0.8 (0.3) [0.1, 1.4]
72 145 6.7 (0.3) 142 6.1 (0.3) 0.6 (0.4) [-0.2, 1.3] 0.6 (0.4) [-0.2, 1.3]
84 143 7.9 (0.3) 141 7.0 (0.3) 0.9 (0.4) [0.0, 1.7] 0.9 (0.4) [0.1, 1.7]
96 142 8.9 (0.3) 139 7.9 (0.3) 1.0 (0.4) [0.1, 1.8] 1.0 (0.4) [0.1, 1.8]
108 124 9.8 (0.4) 122 8.8 (0.4) 1.0 (0.5) [0.0, 2.0] 1.1 (0.5) [0.1, 2.1]
101
120 114 10.8 (0.4) 108 9.7 (0.4) 1.1 (0.6) [-0.1, 2.2] 1.1 (0.6) [-0.0, 2.2]
132 102 12.2 (0.5) 97 10.7 (0.5) 1.5 (0.7) [0.1, 2.9] 1.5 (0.7) [0.1, 2.9]
144 75 11.9 (0.5) 77 11.9 (0.5) 0.0 (0.7) [-1.4, 1.5] 0.0 (0.7) [-1.4, 1.5]
156 42 13.4 (0.7) 48 13.4 (0.7) 0.0 (1.0) [-1.9, 2.0] 0.2 (1.0) [-1.8, 2.1]
168 24 13.3 (1.0) 25 14.2 (1.1) -1.0 (1.4) [-3.8, 1.9] -0.6 (1.5) [-3.6, 2.4]
Table S14.3 ODYSSEY B - Height (cm) change over follow-up

12 195 1.2 (0.1) 198 1.1 (0.1) 0.1 (0.1) [-0.2, 0.4] 0.1 (0.1) [-0.1, 0.4]
24 195 2.2 (0.1) 198 2.0 (0.1) 0.2 (0.2) [-0.2, 0.5] 0.2 (0.2) [-0.2, 0.5]
36 193 3.3 (0.1) 196 3.1 (0.1) 0.3 (0.2) [-0.1, 0.7] 0.3 (0.2) [-0.1, 0.7]
48 193 4.6 (0.2) 195 4.2 (0.2) 0.4 (0.2) [-0.1, 0.8] 0.4 (0.2) [-0.1, 0.8]
60 193 5.5 (0.2) 193 5.2 (0.2) 0.3 (0.3) [-0.3, 0.8] 0.3 (0.3) [-0.3, 0.8]
72 192 6.6 (0.2) 192 6.1 (0.2) 0.5 (0.3) [-0.1, 1.1] 0.5 (0.3) [-0.2, 1.1]
84 189 7.7 (0.3) 192 7.0 (0.3) 0.7 (0.4) [-0.1, 1.4] 0.6 (0.4) [-0.1, 1.3]
96 188 8.7 (0.3) 190 8.0 (0.3) 0.7 (0.4) [-0.1, 1.5] 0.6 (0.4) [-0.1, 1.4]
108 180 9.6 (0.3) 183 8.9 (0.3) 0.8 (0.4) [-0.1, 1.6] 0.7 (0.4) [-0.1, 1.6]
120 147 10.7 (0.4) 144 9.6 (0.4) 1.1 (0.5) [0.0, 2.2] 1.1 (0.5) [0.0, 2.2]
132 113 11.4 (0.5) 116 10.6 (0.5) 0.7 (0.7) [-0.5, 2.0] 0.7 (0.6) [-0.6, 2.0]
144 74 12.3 (0.6) 71 12.0 (0.6) 0.3 (0.9) [-1.4, 2.0] 0.3 (0.8) [-1.3, 2.0]
156 45 13.0 (0.8) 41 11.3 (0.8) 1.7 (1.1) [-0.5, 3.9] 1.7 (1.1) [-0.5, 3.9]
168 17 13.1 (1.2) 14 10.9 (1.4) 2.3 (1.9) [-1.5, 6.1] 2.9 (2.0) [-1.1, 6.9]
138.6 in B.
**Normal regression also adjusted for all stratification factors in addition to baseline Height (cm)
+Linear mixed models fitted with random intercept and fixed effects for treatment group, study visit and adjustment covariates (baseline Height (cm) and stratification factors)
102
Figure S14.1 Total population - Height (cm) change over follow-up
103
Figure S14.2 ODYSSEY A - Height (cm) change over follow-up
104
Figure S14.3 ODYSSEY B - Height (cm) change over follow-up
Table S14.4 Total population - Weight (kg) change over follow-up

12 345 1.4 (0.1) 350 1.0 (0.1) 0.4 (0.1) [0.1, 0.7] 0.4 (0.1) [0.1, 0.7]
24 344 2.4 (0.1) 348 1.8 (0.1) 0.6 (0.2) [0.3, 1.0] 0.6 (0.2) [0.3, 1.0]
36 342 3.4 (0.2) 344 2.6 (0.2) 0.8 (0.2) [0.4, 1.2] 0.8 (0.2) [0.4, 1.2]
48 342 4.1 (0.2) 341 3.4 (0.2) 0.7 (0.2) [0.2, 1.2] 0.7 (0.2) [0.2, 1.2]
60 341 4.9 (0.2) 335 4.2 (0.2) 0.7 (0.3) [0.2, 1.3] 0.8 (0.3) [0.2, 1.3]
72 337 5.6 (0.2) 334 4.8 (0.2) 0.9 (0.3) [0.3, 1.5] 0.9 (0.3) [0.3, 1.5]
84 332 6.5 (0.2) 333 5.5 (0.2) 1.0 (0.3) [0.4, 1.6] 1.0 (0.3) [0.4, 1.6]
105
96 331 7.1 (0.3) 329 6.1 (0.3) 1.0 (0.4) [0.3, 1.7] 1.0 (0.4) [0.3, 1.7]
108 304 7.8 (0.3) 305 7.0 (0.3) 0.8 (0.4) [-0.0, 1.6] 0.8 (0.4) [0.0, 1.5]
120 261 8.7 (0.3) 252 7.6 (0.3) 1.1 (0.5) [0.2, 2.0] 1.1 (0.5) [0.2, 2.0]
132 215 9.6 (0.4) 215 8.5 (0.4) 1.1 (0.5) [-0.0, 2.1] 1.1 (0.5) [0.0, 2.2]
144 149 9.9 (0.5) 150 9.7 (0.5) 0.2 (0.7) [-1.2, 1.6] 0.4 (0.7) [-1.0, 1.7]
156 88 10.8 (0.7) 89 10.9 (0.7) 0.0 (1.0) [-2.0, 2.0] 0.2 (1.0) [-1.7, 2.2]
168 41 11.2 (1.1) 39 12.0 (1.3) -0.8 (1.7) [-4.2, 2.6] -0.2 (1.8) [-3.9, 3.5]
Table S14.5 ODYSSEY A - Weight (kg) change over follow-up

12 150 1.7 (0.2) 152 1.1 (0.2) 0.6 (0.2) [0.1, 1.0] 0.5 (0.2) [0.1, 1.0]
24 149 2.7 (0.2) 150 1.8 (0.2) 0.9 (0.3) [0.3, 1.5] 0.9 (0.3) [0.3, 1.5]
36 149 3.9 (0.3) 148 2.7 (0.3) 1.1 (0.4) [0.4, 1.9] 1.1 (0.4) [0.4, 1.9]
48 149 4.5 (0.3) 146 3.7 (0.3) 0.8 (0.4) [-0.0, 1.6] 0.8 (0.4) [-0.0, 1.6]
60 148 5.5 (0.3) 141 4.5 (0.4) 1.0 (0.5) [0.0, 1.9] 1.0 (0.5) [0.1, 2.0]
72 145 6.3 (0.4) 142 5.2 (0.4) 1.1 (0.5) [0.1, 2.2] 1.2 (0.5) [0.1, 2.2]
84 143 7.2 (0.4) 141 5.8 (0.4) 1.4 (0.6) [0.3, 2.5] 1.5 (0.6) [0.4, 2.5]
96 143 7.8 (0.4) 139 6.5 (0.4) 1.3 (0.6) [0.1, 2.5] 1.4 (0.6) [0.2, 2.5]
108 124 8.5 (0.5) 122 7.4 (0.5) 1.1 (0.7) [-0.3, 2.5] 1.2 (0.7) [-0.2, 2.5]
120 114 9.4 (0.6) 108 8.3 (0.6) 1.0 (0.8) [-0.5, 2.6] 1.1 (0.8) [-0.5, 2.7]
132 102 10.4 (0.6) 98 9.0 (0.6) 1.4 (0.9) [-0.3, 3.2] 1.5 (0.9) [-0.2, 3.2]
144 75 10.0 (0.8) 77 10.0 (0.8) -0.1 (1.0) [-2.1, 2.0] 0.2 (1.0) [-1.8, 2.3]
156 42 11.0 (1.1) 48 11.4 (1.1) -0.4 (1.5) [-3.4, 2.6] 0.1 (1.5) [-2.8, 3.0]
168 24 10.7 (1.5) 25 11.7 (1.7) -1.0 (2.3) [-5.6, 3.5] -0.6 (2.4) [-5.5, 4.3]
Table S14.6 ODYSSEY B - Weight (kg) change over follow-up

12 195 1.2 (0.1) 198 0.9 (0.1) 0.2 (0.2) [-0.1, 0.6] 0.2 (0.2) [-0.1, 0.6]
24 195 2.2 (0.2) 198 1.7 (0.2) 0.4 (0.2) [0.0, 0.9] 0.4 (0.2) [0.0, 0.9]
36 193 3.0 (0.2) 196 2.5 (0.2) 0.6 (0.2) [0.1, 1.0] 0.6 (0.2) [0.1, 1.0]
48 193 3.8 (0.2) 195 3.2 (0.2) 0.6 (0.3) [0.1, 1.2] 0.6 (0.3) [0.1, 1.1]
106
60 193 4.5 (0.2) 194 3.9 (0.2) 0.6 (0.3) [-0.1, 1.2] 0.5 (0.3) [-0.1, 1.2]
72 192 5.1 (0.3) 192 4.5 (0.3) 0.7 (0.4) [-0.1, 1.4] 0.6 (0.4) [-0.1, 1.3]
84 189 6.0 (0.3) 192 5.3 (0.3) 0.7 (0.4) [-0.1, 1.5] 0.7 (0.4) [-0.1, 1.4]
96 188 6.7 (0.3) 190 5.9 (0.3) 0.8 (0.4) [-0.0, 1.7] 0.8 (0.4) [-0.1, 1.6]
108 180 7.3 (0.3) 183 6.7 (0.3) 0.6 (0.5) [-0.3, 1.5] 0.5 (0.5) [-0.4, 1.4]
120 147 8.2 (0.4) 144 7.1 (0.4) 1.1 (0.5) [0.0, 2.2] 1.1 (0.5) [0.0, 2.2]
132 113 9.0 (0.5) 117 8.3 (0.5) 0.7 (0.7) [-0.6, 2.0] 0.7 (0.7) [-0.6, 2.0]
144 74 9.8 (0.6) 73 9.4 (0.6) 0.5 (0.9) [-1.3, 2.3] 0.5 (0.9) [-1.2, 2.3]
156 46 10.6 (0.9) 41 10.2 (1.0) 0.4 (1.3) [-2.2, 3.0] 0.4 (1.3) [-2.1, 3.0]
168 17 11.8 (1.8) 14 12.3 (2.0) -0.5 (2.8) [-6.1, 5.2] 0.4 (2.9) [-5.6, 6.3]
in B.
**Normal regression also adjusted for all stratification factors in addition to baseline Weight (kg)
+Linear mixed models fitted with random intercept and fixed effects for treatment group, study visit and adjustment covariates (baseline Weight (kg) and stratification factors)
107
Figure S14.4 Total population - Weight (kg) change over follow-up
108
Figure S14.5 ODYSSEY A - Weight (kg) change over follow-up
109
Figure S14.6 ODYSSEY B - Weight (kg) change over follow-up
Table S14.7 Total population - BMI-for-age change over follow-up

12 345 0.19 (0.03) 350 0.14 (0.03) 0.06 (0.04) [-0.03, 0.14] 0.06 (0.04) [-0.02, 0.14]
24 344 0.24 (0.03) 347 0.14 (0.03) 0.10 (0.05) [0.01, 0.19] 0.10 (0.05) [0.01, 0.19]
36 342 0.26 (0.03) 344 0.14 (0.03) 0.12 (0.05) [0.02, 0.22] 0.12 (0.05) [0.03, 0.22]
48 342 0.22 (0.04) 340 0.16 (0.04) 0.06 (0.05) [-0.04, 0.16] 0.06 (0.05) [-0.04, 0.16]
60 338 0.26 (0.04) 331 0.17 (0.04) 0.09 (0.05) [-0.01, 0.19] 0.09 (0.05) [-0.01, 0.19]
72 332 0.24 (0.04) 328 0.12 (0.04) 0.12 (0.06) [0.00, 0.23] 0.12 (0.06) [0.01, 0.23]
84 322 0.26 (0.04) 325 0.14 (0.04) 0.12 (0.06) [0.01, 0.23] 0.12 (0.06) [0.01, 0.23]
110
96 312 0.24 (0.04) 316 0.11 (0.04) 0.13 (0.06) [0.01, 0.25] 0.13 (0.06) [0.01, 0.25]
108 283 0.23 (0.05) 286 0.15 (0.05) 0.07 (0.06) [-0.05, 0.20] 0.07 (0.06) [-0.05, 0.20]
120 236 0.24 (0.05) 228 0.10 (0.05) 0.14 (0.07) [-0.01, 0.28] 0.13 (0.07) [-0.02, 0.27]
132 184 0.24 (0.06) 187 0.09 (0.06) 0.14 (0.09) [-0.03, 0.32] 0.14 (0.09) [-0.03, 0.32]
144 120 0.24 (0.08) 122 0.09 (0.08) 0.14 (0.11) [-0.08, 0.37] 0.15 (0.12) [-0.08, 0.37]
156 70 0.22 (0.12) 72 0.27 (0.11) -0.05 (0.16) [-0.38, 0.27] -0.03 (0.17) [-0.36, 0.30]
168 34 0.32 (0.18) 29 0.33 (0.20) 0.01 (0.27) [-0.53, 0.54] -0.02 (0.28) [-0.59, 0.56]
Table S14.8 ODYSSEY A - BMI-for-age change over follow-up

12 150 0.3 (0.0) 152 0.2 (0.0) 0.1 (0.1) [-0.0, 0.2] 0.1 (0.1) [-0.0, 0.2]
24 149 0.3 (0.1) 149 0.1 (0.1) 0.2 (0.1) [0.0, 0.3] 0.2 (0.1) [0.0, 0.3]
36 149 0.4 (0.1) 148 0.2 (0.1) 0.2 (0.1) [0.1, 0.4] 0.2 (0.1) [0.1, 0.4]
48 149 0.3 (0.1) 145 0.3 (0.1) 0.1 (0.1) [-0.1, 0.3] 0.1 (0.1) [-0.1, 0.3]
60 148 0.4 (0.1) 140 0.2 (0.1) 0.1 (0.1) [-0.0, 0.3] 0.1 (0.1) [-0.0, 0.3]
72 145 0.4 (0.1) 139 0.2 (0.1) 0.2 (0.1) [-0.0, 0.4] 0.2 (0.1) [-0.0, 0.4]
84 139 0.4 (0.1) 137 0.2 (0.1) 0.2 (0.1) [0.0, 0.4] 0.2 (0.1) [0.0, 0.4]
96 135 0.4 (0.1) 133 0.2 (0.1) 0.2 (0.1) [-0.0, 0.4] 0.2 (0.1) [-0.0, 0.4]
108 116 0.4 (0.1) 112 0.3 (0.1) 0.1 (0.1) [-0.1, 0.3] 0.1 (0.1) [-0.1, 0.4]
120 102 0.4 (0.1) 94 0.3 (0.1) 0.1 (0.1) [-0.1, 0.4] 0.1 (0.1) [-0.1, 0.4]
132 89 0.4 (0.1) 80 0.2 (0.1) 0.2 (0.1) [-0.1, 0.5] 0.2 (0.1) [-0.1, 0.5]
144 61 0.3 (0.1) 59 0.2 (0.1) 0.1 (0.2) [-0.2, 0.5] 0.1 (0.2) [-0.2, 0.5]
156 34 0.2 (0.2) 37 0.2 (0.2) -0.0 (0.2) [-0.5, 0.4] -0.0 (0.2) [-0.5, 0.4]
168 20 0.1 (0.2) 15 0.1 (0.3) 0.0 (0.4) [-0.7, 0.8] -0.1 (0.4) [-0.9, 0.7]
Table S14.9 ODYSSEY B - BMI-for-age change over follow-up

12 195 0.10 (0.04) 198 0.10 (0.04) 0.01 (0.05) [-0.10, 0.11] 0.01 (0.05) [-0.10, 0.11]
24 195 0.17 (0.04) 198 0.13 (0.04) 0.04 (0.06) [-0.08, 0.16] 0.04 (0.06) [-0.08, 0.16]
36 193 0.17 (0.04) 196 0.11 (0.04) 0.06 (0.06) [-0.06, 0.18] 0.06 (0.06) [-0.06, 0.18]
48 193 0.14 (0.04) 195 0.09 (0.04) 0.05 (0.06) [-0.07, 0.17] 0.05 (0.06) [-0.07, 0.17]
111
60 190 0.16 (0.05) 191 0.10 (0.05) 0.06 (0.06) [-0.07, 0.19] 0.06 (0.06) [-0.07, 0.18]
72 187 0.13 (0.05) 189 0.04 (0.05) 0.09 (0.07) [-0.04, 0.23] 0.09 (0.07) [-0.04, 0.22]
84 183 0.16 (0.05) 188 0.09 (0.05) 0.07 (0.07) [-0.07, 0.20] 0.07 (0.07) [-0.07, 0.20]
96 177 0.14 (0.05) 183 0.04 (0.05) 0.11 (0.08) [-0.05, 0.26] 0.10 (0.08) [-0.05, 0.25]
108 167 0.11 (0.06) 174 0.07 (0.06) 0.04 (0.08) [-0.12, 0.20] 0.03 (0.08) [-0.12, 0.19]
120 134 0.12 (0.07) 134 -0.01 (0.07) 0.14 (0.09) [-0.04, 0.32] 0.12 (0.09) [-0.06, 0.30]
132 95 0.12 (0.08) 107 0.01 (0.08) 0.11 (0.11) [-0.12, 0.33] 0.12 (0.11) [-0.10, 0.34]
144 59 0.19 (0.11) 63 0.04 (0.11) 0.15 (0.16) [-0.17, 0.46] 0.16 (0.16) [-0.16, 0.48]
156 36 0.20 (0.17) 35 0.32 (0.17) -0.12 (0.24) [-0.60, 0.36] -0.09 (0.24) [-0.57, 0.40]
168 14 0.44 (0.28) 14 0.62 (0.29) -0.18 (0.40) [-1.00, 0.65] -0.04 (0.42) [-0.91, 0.83]
*Change calculated using normal regression adjusting for baseline and in total ODYSSEY A and B strata only. Presenting mean change from a baseline of -0.7 in total, -0.6 in A, and -0.8 in
B.
**Normal regression also adjusted for all stratification factors in addition to baseline BMI-for-age
+Linear mixed models fitted with random intercept and fixed effects for treatment group, study visit and adjustment covariates (baseline BMI-for-age and stratification factors)
112
Figure S14.7 Total population - BMI-for-age change over follow-up
113
Figure S14.8 ODYSSEY A - BMI-for-age change over follow-up
114
Figure S14.9 ODYSSEY B - BMI-for-age change over follow-up
115
S 15 Biochemistry
data at baseline.
Table S15.1 Total population - Creatinine changes over follow-up

4 348 0.06 (0.01) 349 0.00 (0.01) 0.06 (0.01) [0.04, 0.08] 0.06 (0.01) [0.04, 0.08]
24 344 0.07 (0.01) 346 0.01 (0.01) 0.07 (0.01) [0.05, 0.08] 0.06 (0.01) [0.05, 0.08]
48 342 0.08 (0.01) 338 0.03 (0.01) 0.06 (0.01) [0.04, 0.08] 0.06 (0.01) [0.04, 0.08]
72 342 0.11 (0.01) 337 0.05 (0.01) 0.06 (0.01) [0.04, 0.08] 0.06 (0.01) [0.04, 0.08]
96 339 0.12 (0.01) 332 0.04 (0.01) 0.08 (0.01) [0.06, 0.11] 0.08 (0.01) [0.06, 0.10]
Table S15.2 ODYSSEY A - Creatinine over follow-up

4 153 0.07 (0.01) 152 -0.02 (0.01) 0.09 (0.02) [0.05, 0.12] 0.09 (0.02) [0.05, 0.12]
24 150 0.08 (0.01) 150 -0.01 (0.01) 0.10 (0.02) [0.06, 0.13] 0.09 (0.02) [0.06, 0.12]
48 150 0.09 (0.01) 146 -0.00 (0.01) 0.09 (0.02) [0.06, 0.12] 0.09 (0.02) [0.06, 0.12]
72 148 0.12 (0.01) 145 0.02 (0.01) 0.10 (0.02) [0.07, 0.13] 0.10 (0.02) [0.07, 0.13]
96 147 0.14 (0.01) 140 0.02 (0.01) 0.12 (0.02) [0.08, 0.15] 0.11 (0.02) [0.08, 0.15]
Table S15.3 ODYSSEY B - Creatinine over follow-up

4 195 0.05 (0.01) 197 0.02 (0.01) 0.04 (0.01) [0.01, 0.06] 0.04 (0.01) [0.01, 0.06]
24 194 0.06 (0.01) 196 0.02 (0.01) 0.04 (0.01) [0.02, 0.07] 0.04 (0.01) [0.02, 0.07]
48 192 0.08 (0.01) 192 0.05 (0.01) 0.04 (0.01) [0.01, 0.06] 0.04 (0.01) [0.01, 0.06]
72 194 0.10 (0.01) 192 0.07 (0.01) 0.03 (0.01) [0.00, 0.05] 0.03 (0.01) [0.00, 0.05]
96 192 0.11 (0.01) 192 0.05 (0.01) 0.06 (0.01) [0.03, 0.09] 0.06 (0.01) [0.03, 0.09]
116
*Change calculated using normal regression adjusting for baseline and in total ODYSSEY A and B strata only. Presenting mean change from a baseline of 0.5 in total, 0.5 in A, and 0.5 in
B.
**Normal regression also adjusted for all stratification factors in addition to baseline Creatinine
+Linear mixed models fitted with random intercept and fixed effects for treatment group, study visit and adjustment covariates (baseline Creatinine and stratification factors)
Figure S15.1 Total population - Creatinine changes over follow-up
117
Figure S15.2 ODYSSEY A- Creatinine changes over follow-up
118
Figure S15.3 ODYSSEY B- Creatinine changes over follow-up
119

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Supplementary Appendix

S1 ODYSSEY Trial Team ........................................................................................................................................... 6

Clinical Trial Units

Baylor College of Medic Adeodata R. Kekitiinwa, Pauline Amuge, Dickson

PK substudies: David Burger, Pauline Bollen, Angela Colbers, Hylke Waalewijn.

Per protocol population

S3.2 Primary endpoint

Death due to any cause

Handling viral load data

, the date of the next scheduled

the confirmatory measure. Where a patient

Analysis details for primary efficacy outcome

Further details in Statistical Analysis Plan.

Sensitivity analyses for primary endpoint

i. c/ml, with a treatment switch for

Per protocol and secondary analyses

*, by comparing the primary

Sub-group analyses were pre-specified as follows:

S3.3 FDA snapshot algorithm

Was there at least one viral load*

Did the participant switch

Did the participant switch

Did the participant die or switch

Was the last viral load Yes

*Off ART viral loads will be excluded from algorithm.

S3.6 Definition of treatment change

S3.7 Testing multiple outcomes

S3.8 Impact of COVID-19

S 4 Dolutegravir dosing throughout ODYSSEY

¥ 20mg FCT approved by EMA in children weighing 15 to <20kg only

S 5 Enrolment and eligibility

819 children assessed for eligibility

109 determined ineligible:

710 underwent randomization

3 children randomized in error:

350 included in analyses** 357 included in analyses**

340 children assessed for eligibility

313 underwent randomization

2 children excluded for major ineligibility:

154 included in analyses** 157 included in analyses**

479 children assessed for eligibility

397 underwent randomization

1 child excluded for major ineligibility:

196 included in analyses** 200 included in analyses**

**Mean of measurement at screening and randomisation if both are available

Table S6.2 Baseline characteristics: Antiretroviral exposure [ODYSSEY B only]

*Adjusted for ODSSEY A and B strata only in total, unadjusted in A and B.

Table S7.2 Incidence of clinical or virological failure by 48 weeks

*Adjusted for ODSSEY A and B strata only in total, unadjusted in A and B

**Adjusted all for stratification factors (primary analysis)

*Adjusted for ODSSEY A and B strata only in total, unadjusted in A and B

Table S7.6 Incidence of clinical or virological failure by 144 weeks

[95% Confidence Interval] [-12.8, -0.5] [-13.7, 4.2] [-16.5, 0.3]

Figure S7.5 Sensitivity analysis: censoring at time of ART switch for

Table S7.15 Total population - Subgroup analyses for primary endpoint

Table S7.16 ODYSSEY A - Subgroup analyses for primary endpoint

Table S7.17 ODYSSEY B - Subgroup analyses for primary endpoint

350 included in analyses 357 included in analyses

154 included in analyses 157 included in analyses

196 included in analyses 200 included in analyses