Short Communication: Reduced Nevirapine Concentrations Among HIV-Positive Women Receiving Mefloquine for Intermittent Preventive Treatment for Malaria Control During Pregnancy

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 high-performance 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.

Chemoprevention for malaria with monthly intermittent preventive treatment with dihydroartemisinin–piperaquine in pregnant women living with HIV on daily co-trimoxazole in Kenya and Malawi: a randomised, double-blind, placebo-controlled trial

“… 5 , 6 , 17 Furthermore, significant drug–drug interactions between mefloquine and nevirapine resulted in reduced nevirapine plasma concentrations, which might have contributed to the increased risk of mother-to-child transmission of HIV in the co-trimoxazole plus mefloquine group compared with co-trimoxazole alone. 7 …”

“… 4 , 5 However, IPTp with mefloquine was poorly tolerated 5 , 6 and was associated with increased viral load and mother-to-child transmission of HIV, 5 possibly reflecting a drug–drug interaction between mefloquine and nevirapine. 7 IPTp with dihydroartemisinin–piperaquine has only been assessed in a small trial of 200 pregnant women living with HIV receiving efavirenz-based cART in Uganda. 8 The study was inconclusive.…”

Drugs for Intermittent Preventive Treatment of Malaria in Pregnancy: Current Knowledge and Way Forward

“…Importantly, the same trial reported a two-fold increased risk of mother-to-child transmission (MTCT) of HIV among infants born to MQ recipients [29]. It has been hypothesized that this finding is due to a reduction in the concentration of nevirapine linked to the uptake of MQ [100].…”

Drug–Drug Interactions with Antiretroviral Drugs in Pregnant Women Living with HIV: Are They Different from Non-Pregnant Individuals?

“…Haaland et al examined ARV plasma concentrations in a group of pregnant women living with HIV co-treated with mefloquine, which showed a high rate of mother-to-child transmission [102]. A significant reduction in median nevirapine concentrations (approximately 25%) was observed in pregnant women receiving co-treatment with mefloquine, although the nevirapine concentrations remained above the previously reported target values to prevent HIV replication [102]. This reduction was not observed in pregnant women receiving nevirapine with placebo.…”