ART Treatment Failure

Clinical Pharmacology
Dr A Reid & Dr M Munyoro
Community Medicine
Dr J Chirenda
Community Health Care Nursing
Sr G Mugadza
 Outline of Presentation
• Definition of ART failure
• Drivers of ART failure
• Case studies
• Nurse’s Role in ART care
• Public health implications of ART failure
• Question and answer
 Reminder
Definition of ART Failure
• Virologic failure is defined as repeated instances of a plasma viral load
≥200 copies/mL after 6 months of therapy. Laboratory results must be
confirmed with repeat testing before a final assessment of virologic
failure is made. (Zim guidelines=>1000copies/mL)
• Immunologic failure refers to a suboptimal immunologic response to
therapy or an immunologic decline while on therapy, but there is no
standardized definition
• Clinical failure refers disease progression despite favourable immunologic
and virologic responses to ART
• https://aidsinfo.nih.gov/guidelines,2019
Viral Load >1,000 copies/ml means
Treatment Failure when…
Viral load >
1000
copies/ml

2 Regimen failure or
consecutive
times treatment failure
indicates possible drug
3 months resistance
apart

With good
the 1,2,3 Rule adherence
in between

4
Goal of ART

Goal of ART is to inhibit / stop viral replication leading to:

• Recovery of the immune system
• Reduction in HIV associated morbidity and mortality
• Reduction in HIV transmission
Epidemiological overview
• Historical background
• ART provision started 2004/5 with 3 sites
• Low enrolment due to limited resources
• Gradual rollout with PMCT sites offering ART to pregnant women and
children
• Now programme adopted test and treat
 Clients currently on ART by regimen as at Dec 2018
Output Primary Care District / Mission Provincial Central Total
level Hospitals Hospitals Hospitals

Total HIV pts in Care 926,711 206,381 26,018 22,022 1,181,132

Number on ART
902,347 200,955 25,334 21,443 1,150,079

Number Newly initiated on ART

106,266 15,332 2,180 2,990 126,768

Number of patients on:

First line
873,334 190,169 23,655 19,005 1,106,163

Second line 29,011 10,739 1,678 2,286 43,714

Third line 0 111 0 91 202

A total of 1,150,079 patients receiving ART by Dec, 2018; Majority (78.5%) of ART patients
receiving care at primary care level; 4% on Second line ART and only 202 on Third line ART
Treatment Failure….

• Perhaps it’s the ART….

NNRTI resistance
• Common in previously ARV exposed patients
• 2014-2016 PDR survey in 11 countries including Zimbabwe , 21.6%, 95% CI
13.8–32.2 in previously exposed versus 8.3%, 95% CI 6.0–11.4 in ARV naïve
patients; P<0.0001).
• In South Africa, 63.7% (95% CI 59.0–68.4) in HIV exposed infants
• Systematic literature review (2014 to 2017 studies)
• 49.3%, among PMTCT exposed children
• BUT also in recently HIV infected people (ZIMPHIA study)
• Malawi, 4 out of 26 and Zimbabwe 2 out of 30 individuals
• Duration of treatment also increases NNRTI resistance
• 4.3%-16.7% in patients on treatment for 12-24 months
• 4.2% to 28.3% among patients on for 36–48+ months
Resistance to Protease Inhibitors
• HIV virus will require multiple protease mutations to become fully
resistant.
• Common on patients with poor adherence
• Co-administration with Ritonavir delays development of resistance
• High genetic barrier to drug resistance
Case 1: Grace
18 year old double orphan
• Vertically acquired HIV
• Age 2 years: father dies
• Age 3 years: mother dies
• 14 years: disclosure of HIV status
• 16 years: Aunty loses job – goes to live with maternal
grandmother
• 18 years: Maternal grandmother dies

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Case 1: Grace
19 years:
• Deep depression
• Stops ART
• Develops disseminated TB – treated
• Admitted to HDU on Christmas eve with severe pneumonia

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Case 1: Grace
• Climbs stairs to Clinic Director
• Referral to youth psychiatrist
• Talk therapy and tricylic antidepressant for 6 months
• Out of depression
• Back on ART
• Back to school
• Started “Speed” support group
• Started University studying BSc Social Science

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Case 2: Patrick
• 45 year old married labourer on 3rd line ART
• October 2016 admitted with treatment failure: severe pneumonia and
CD4 of 80 cells/mm3
• Had defaulted ART for 4 months due to marital discord  anger and
depression
• Restarted ART after admission

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Case 2: Patrick
• June 2017: admitted with Cryptococcal meningitis and CD4 of
2/mm3
• Had defaulted clinic attendance and ART for 6 months
• Anger and depression due to being made redundant leading to
severe food security issues and further marital discord
• Treated, counselled, job back
• Out of depression, food security improved
• Died 6 months later from recurrent Cryptococcal Meningitis

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Case 3: Tinashe
• 27 year old single unemployed male from rural Seke, vertically
acquired HIV
• Presented with clinical treatment failure and disseminated TB,
CD4 = 68
• Isolated
• Father died when he was 2 years old
• Twin brother died of HIV when he was 14
• Fathered a child by a 17 year old HIV positive girl but she left
him for someone else- “no money “
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Case 3: Tinashe

• Sunk into severe depression leading to abuse of alcohol &

“musombodia”
• On second-line ATV/r ART, but CD4 count dropped to 68 and VL
20,000 and lost weight…? 2nd Line ART Failure
• Admitted to Pari Annex for alcohol detox for one month, treated for
severe depression with Fluoxetine and family counselling

• Transferred to Newlands Clinic for ? 3rd line ART

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Case 3 : Tinashe
• Program of intensified adherence counselling and joining young adult
male support group
• Did well. Stayed off alcohol & drugs
• VL & CD4 gradually increased
• About 8 months later relapsed with alcohol abuse
• Readmitted for detox to Pari Annex for one month

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Case 3 : Tinashe
• Off alcohol now for 18 months
• Viral Load completely suppressed and CD4 count above 120
• Getting involved in leading support groups for teens

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Cases 1 & 2 & 3
• What do they have in common?
• Psycho-social risk factors causing them to not adhere to
ART
• Multiple losses  anger, grief and depression
• Marital discord  anger and depression
• Unemployment  serious finance and food security issues
 anger and depression
• Substance abuse
• Isolation, lack of supports
• Lack of follow-up and retention in care

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NURSE’S ROLE
Holistic Model of Care for Preventing ART Failure
• Nurses are the first health care providers for the majority of clients/
patients and HIV & AIDS is not exceptional.
• Uses the holistic model of care by looking at the human being is a
complex entity
• Hence the nurse views every client/ patient in his totality if ART treatment is to be
a success.
• Holistic care entails attending to the physical,
Psychological, Spiritual and socioeconomic needs of the
client in order to promote quality of life
ART TREATMENT FAILURE ISSUES
 Patient may not ready? – he/she may be non-
adherent

 Patient may not understand the drugs? – he/she may

take them incorrectly
 Patient may not expect side effects? – he/she may be
shocked and get ‘put off’ ARVs or not report any
problems

 Patient may be feeling lonely and unsupported? –

he/she may be frightened, reluctant to take drugs or
to report any problems
ASSESSING CLIENT READINESS FOR ART

By exploring factors like:

• How comfortable and willing is the patient to start
ART
• Why a patient may decide not to take ART
• Possible barriers to ART adherence and how they can
be addressed
CLIENT EDUCATION

Outlines the basics of HIV and HIV disease progression,

including what is HIV, what is AIDS, basics of
transmission, HIV disease progression and HIV myths.
ADDRESSING ART ADHERENCE
ISSUES
• Educate on adherence
• Significance of adherence
• Factors that affect adherence
• Strategies to overcome challenges of adherence
CLIENT ASSESSMENT

Is patient experiencing any side

effects? How are they feeling?
Any problems?
Any social support systems in place
Lack of social support impacts negatively on ART
treatment as client must navigate through a complex
care process so as to achieve optimum health
( Gardener, Mc Lees, Steiner, Del Rio & Burman, 2011).
FOLLOW UP CARE
Through:
• Community health nurses
• Peer support groups
• Village health workers
• Phone calls
• Messaging
• Whats app
COUNSELLING

Counselling addresses issues associated with substance

abuse and depression as they are critical predictors of
treatment failure in HIV disease (Hawkins, 2019).
NURSE’S ROLES: SUMMARY

MA
NAG
E
COUNSEL
ASSESSMENT

CLIENT

REFER EDUCATE
FO
LL
O
W
UP
 What are the Public Health
Implications of ART Failure?
Goal of ART

Goal of ART is to inhibit / stop viral replication leading to:

• Recovery of the immune system
• Reduction in HIV associated morbidity and mortality
• Reduction in HIV transmission
Causes of HIV Treatment Failure

Structural
Program
Clinic
Provider
Patient
Viral
Drivers of ARV Resistance
• Largely man-made
• Programmatic
• Patient level
Programmatic Causes
• Erratic supply of antimicrobial agents
• Supply of poor quality antimicrobial agents
• Inadequate monitoring of treatment
• Drug-drug interactions and adverse drug events
• Genetic predisposition
Implications of ART Failure: Costs
Facility type Cost ($)
Primary 116,097
Secondary 300,162
Tertiary 613,558
Quarternary 1,384,125
Source: Prevention of Mother-to-Child Transmission (PMTCT) and And
antiretroviral Treatment (ART) Services Cost evaluation in Zimbabwe report,
2018
Sources of high costs
• New medicines
• Train and re-train health care workers
• Supply chain management
• Prevention of new infections
Prevention and control of ART Failure
• Everyone has a responsibility
• Patient (well described by my colleagues)
• Programmatic (provider)
• Viral
• Non-health sector responsibilities Structural
Program
• Finance
Clinic
• Social Welfare Provider
• Local Government Patient
Viral
Acknowledgements
• Newlands clinic (Dr Chimbetete)
• Dr Choto – MOH
• Dr TD Chawana
• Prof HA Mujuru
Resources
1. Rufu A, Chitimbire VTS, Nzou C, et al. Implementation of the 'Test and Treat'
policy for newly diagnosed people living with HIV in Zimbabwe in 2017. Public
Health Action. 2018;8(3):145–150. doi:10.5588/pha.18.0030
2. Chawana, Tariro & A, Reid & T, Bwakura & Gavi, Samuel & C.F.B, Nhachi.
(2014). Factors Influencing Treatment failure in HIV Positive Adult Patients on
First Line Antiretroviral Therapy. The Central African Journal of Medicine. 60.
3. Chawana, T. D., Katzenstein, D., Nathoo, K., Ngara, B., & Nhachi, C. F. B. (2017).
Evaluating an enhanced adherence intervention among HIV positive adolescents
failing atazanavir/ritonavir-based second line antiretroviral treatment at a public
health clinic. Journal of AIDS and HIV Research, 9(1), 17-30.
4. WHO HIV Drug resistance report 2017
Questions ?