Pharmacokinetics of lopinavir/ritonavir and efavirenz in food insecure HIV-infected pregnant and breastfeeding women in Tororo, Uganda
Bartelink, I.H.; Savic, R.M.; Mwesigwa, J.; Achan, J.; Clark, T.; Plenty, A.; Charlebois, E.; Kamya, M.; Young, S.L.; Gandhi, M.; Havlir, D.; Cohan, D.; Aweeka, F.
Journal of Clinical Pharmacology 54(2): 121-132
2014
ISSN/ISBN: 1552-4604 PMID: 24038035 DOI: 10.1002/jcph.167Document Number: 639941
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/m(2) . 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.
Document emailed within 0-6 h
