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- Title
Pharmacokinetics of lopinavir/ritonavir and efavirenz in food insecure HIV-infected pregnant and breastfeeding women in tororo, uganda.
- Authors
Bartelink, Imke H.; Savic, Rada M.; Mwesigwa, Julia; Achan, Jane; Clark, Tamara; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Young, Sera L.; Gandhi, Monica; Havlir, Diane; Cohan, Deborah; Aweeka, Francesca
- Abstract
Pregnancy and food insecurity may impact antiretroviral (ART) pharmacokinetics (PK), adherence and response. We sought to quantify and characterize the PK of lopinavir/ritonavir (LPV/r) and efavirenz (EFV) by pregnancy and nutritional status among HIV-infected women in Tororo, Uganda. In 2011, 62/225 ante-partum/post-partum single dried blood spot samples DBS and 43 post-partum hair samples for LPV/r were derived from 116 women, 51/194 ante-/post-partum DBS and 53 post-partum hair samples for EFV from 105 women. Eighty percent of Ugandan participants were severely food insecure, 26% lost weight ante-partum, and median BMI post-partum was only 20.2 kg/m2. Rich PK-data of normally nourished (pregnant) women and healthy Ugandans established prior information. Overall, drug exposure was reduced (LPV −33%, EFV −15%, ritonavir −17%) compared to well-nourished controls ( P < 0.001), attributable to decreased bioavailability. Pregnancy increased LPV/r clearance 68% ( P < 0.001), whereas EFV clearance remained unchanged. Hair concentrations correlated with plasma-exposure ( P < 0.001), explaining 29% PK-variability. In conclusion, pregnancy and food insecurity were associated with lower ART exposures in this cohort of predominantly underweight women, compared to well-nourished women. Much variability in plasma-exposure was quantified using hair concentrations. Addressing malnutrition as well as ART-PK in this setting should be a priority.
- Subjects
UGANDA; BREASTFEEDING; HIV infections; PREGNANCY; RESEARCH funding; WEIGHT loss; BODY mass index; FOOD security; LOPINAVIR-ritonavir; DESCRIPTIVE statistics; EFAVIRENZ
- Publication
Journal of Clinical Pharmacology, 2014, Vol 54, Issue 2, p121
- ISSN
0091-2700
- Publication type
Article
- DOI
10.1002/jcph.167