Abstract:
Clinical trials demonstrated intermittent preventive treatment in pregnancy with
mefloquine (MQ) reduced malaria rates among pregnant women, yet an unexpected
higher risk of mother-to-child transmission (MTCT) of HIV among HIV-positive women
receiving MQ has also been observed. To determine if interactions between antiretroviral
drugs (ARVs) and MQ could contribute to the increased MTCT observed in women
receiving MQ, we performed a retrospective cross-sectional analysis of ARV plasma
concentrations in peripheral blood (maternal plasma) and cord blood (cord plasma)
collected at delivery from 186 mothers participating in a randomized clinical trial of MQ
(n = 102) compared with placebo (n = 84) in Kenya. Plasma zidovudine (AZT),
lamivudine (3TC), and nevirapine (NVP) concentrations were measured by highperformance liquid chromatography-tandem mass spectrometry. Although only 4%
(7/186) reported not using these ARVs, AZT, 3TC, and NVP were all below the limit of
detection in 44% of maternal plasma and 42% of cord plasma samples, and proportions
were similar between the two study arms. Median concentrations of AZT and 3TC were
not significantly lower in the MQ arm compared with the placebo arm for maternal
plasma and cord plasma (p > .05). However, median NVP concentrations were
significantly lower in the MQ study arm compared with the placebo study arm in both
maternal plasma (1,597 ng/mL vs. 2,353 ng/mL, Mann-Whitney Rank Sum, p = .023)
and cord plasma (2,038 ng/mL vs. 2,434 ng/mL, p = .048). Reduced NVP concentrations
in maternal and cord plasma of women receiving MQ suggest MQ may affect NVP
metabolism for both mother and infant. These results highlight the need to evaluate
potential drug-drug interactions between candidate antimalarials and ARVs for use in
pregnant women.