Can Antimalarial-antiretroviral Interactions Increase Mother-to-Child HIV Transmission in Pregnancy?
BACKGROUND: In malaria-endemic Africa, women living with HIV receive daily treatment with an antibiotic, called cotrimoxazole, which helps to prevent malaria and other opportunistic diseases. However, malaria parasites are becoming resistant to cotrimoxazole. A new malaria treatment, called dihydroartemisinin-piperaquine (DP), is well tolerated, as add on therapy to cotrimoxazole, and has shown great promise for preventing malaria in pregnancy.
GAP: It is unclear if coadministration of DP and a newer antiretroviral treatment, dolutegravir-based antiretroviral therapy (ART), in pregnant women living with HIV, would not result in altered dolutegravir concentrations in the blood to an extent (<300mg/dL) that could increase risk of mother-to-child HIV transmission.
HYPOTHESIS: Coadministration of DP and dolutegravir-based ART leads to a reduction in dolutegravir blood concentrations, to an extent (<300 ng/mL) that could increase the risk of mother-to-child HIV transmission and pharmacokinetic modelling techniques can optimize dolutegravir-ART dosing in this sub-population.
METHODS: This is a cohort study of 17 pregnant women living with HIV in Malawi and on ART, acting as their own-controls in the two-treatment periods. Frequent blood samples will be collected over a course of 24 hours; while on dolutegravir-based ART alone, and when on combined dolutegravir-ART and DP treatments. The primary outcome will be a comparison of the average dolutegravir concentrations, when administered alone, and when coadministered with DP.
IMPACT: Findings from this study will contribute to the pool of evidence needed to inform malaria prevention in pregnant women living with HIV while optimising antiretroviral (dolutegravir) dosing to prevent in-utero vertical HIV transmission.