Intermittent preventive treatment (IPT) of malaria in pregnancy with

mefloquine may reduce nevirapine levels among HIV-infected women

Linda Stoeger1, Anifa Valá2, Esperança Sevene2,3, Mercè Brunet4, Arsénio Nhacolo2, Eusébio Macete2, Clara Menéndez1,2, Raquel González 1,2

1 ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain · 2 Manhiça Health Research Center (CISM), Manhiça, Mozambique · 3 Eduardo Mondlane University, Maputo, Mozambique ·
4 Department of Toxicology and Pharmacology, Hospital Clínic of Barcelona, Barcelona, Spain

BACKGROUND METHODS
Study design and population
Malaria and HIV in pregnancy
• Observational study
• In sub-Saharan Africa, one million
• 249 pregnant women with HIV enrolled from 2010 to 2012 in the MiPPAD trial
pregnancies are complicated by
Mozambique (Figure 1).
malaria and HIV co-infections each
year. (1)
Analysis
• Intermittent preventive treatment in • Plasma concentrations of Nevirapine (NVP), Zidovudine (AZT) and
pregnant women (IPTp) with Lamivudine (3TC) measured by ultra-performance liquid chromatography–
sulphadoxine-pyrimethamine (SP) is tandem mass spectrometry (UPLC–MS/MS) with lower limits of
contraindicated in women with HIV on quantification of 2.5ng/mL.
cotrimoxazole prophylaxis. (2) • ARV drug levels compared between study arms (MQ vs Placebo) and
according to MTCT.
MiPPAD trial
• A randomized placebo-controlled
clinical trial assessed safety and
efficacy of Mefloquine (MQ) for IPTp
in pregnant women with HIV. While
effective in preventing malaria, MQ
was associated with HIV mother-to-
child transmission (MTCT). (3)
Study aim
• Sub-study in Kenya: MQ associated To assess potential pharmacologic
with reduced nevirapine levels in interactions between MQ and
plasma samples indicating potential antiretroviral (ARV) drugs in plasma
effects on nevirapine metabolism in samples of women and infants
mother and infant. (4) participating in the MiPPAD trial in
Mozambique.

RESULTS Figure 1. Study population

ARV levels by treatment arm a) b)

No significant differences of ARV concentrations were observed in maternal and
cord plasma between treatment arms.

ARV levels by MTCT

Lower NVP levels in cord plasma were marginally associated with MTCT (483.96
ng/mL [SD 670.72] vs 883.28 ng/mL [SD 1175.06], p = 0.049).

ARV by treatment arm in MTCT+ group

Within the group of children with HIV, a tendency of reduced NVP levels in the MQ
(344.64 ng/mL [SD 558.99]) vs placebo arm (926.4 ng/mL [SD 619.67]) was
observed in maternal plasma samples (p=0.054).

Overall Placebo MQ Figure 2. Nevirapine concentrations a) in cord blood according to HIV transmission; b) in
(n = 249) (n = 121) (n = 128) venous blood by treatment arm in HIV transmission group
n (%) or median (IQR) n (%) or median (IQR) n (%) or median (IQR)

Age 26 (22-30.5) 26 (22-30) 27 (22-31)

Mid-Upper Arm
Circumference, cm
26.25 (25-28) 27 (25-28) 26 (25-28) CONCLUSIONS
Body Mass Index, kg/m² 23.17 (21.63-25.55) 23.15 (21.66-25.63) 23.18 (21.62-25.55) Findings
While overall, there was no significant correlation between levels of NVP, 3TC and
HIV Viral Load, copies/mL 12555 (1730-53461) 12513.5 (1800-40373) 12807 (1730-56092) AZT and treatment arms, within the MTCT group, we found a tendency of reduced
NVP in maternal plasma in the MQ arm. Further analysis is needed in order to assess
CD4 Lymphocyte Count, 422 (283-594) 419 (290-593) 432.5 (283-594) possible pharmacologic interactions between NVP and MQ.
cells/µL Limitations: High proportion of samples with undetectable ARV concentrations.
ARV treatment (yes) 99 (39.76) 47 (38.84) 52 (40.63)
Previous Gestations Outlook
0 26 (10.48) 13 (10.74) 13 (10.24) Combined analysis of samples from study sites in Kenya and Mozambique.
1-3 168 (67.74) 89 (73.55) 79 (62.20) Further pharmacologic analyses needed in view of novel ARV and IPTp drugs.
4 or more 54 (21.77) 19 (15.70) 35 (27.56)

Table 1. Characteristics of participants at baseline

REFERENCES
(1) González R et al.. HIV and malaria interactions: where do we stand? Expert Rev Anti Infect Ther. 2012;10(2):153-65. (2) Desai M et al.. Prevention of malaria in pregnancy. Lancet Infect Dis [Internet]. 2018;18(4):e119–32. (3) González R et al.
Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial. PLOS Med. 2014;11(9):e1001735. (4) Haaland RE et
al. Short Communication: Reduced Nevirapine Concentrations Among HIV-Positive Women Receiving Mefloquine for Intermittent Preventive Treatment for Malaria Control During Pregnancy. AIDS Res Hum Retroviruses. 2018;34(11):912–5.