Premium
Pharmacokinetics of lopinavir/ritonavir and efavirenz in food insecure HIV‐infected pregnant and breastfeeding women in tororo, uganda
Author(s) -
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
Publication year - 2014
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.167
Subject(s) - efavirenz , lopinavir , medicine , ritonavir , pregnancy , underweight , lopinavir/ritonavir , nevirapine , pharmacokinetics , breastfeeding , obstetrics , bioavailability , physiology , postpartum period , malnutrition , viral load , human immunodeficiency virus (hiv) , pharmacology , pediatrics , antiretroviral therapy , immunology , obesity , biology , genetics , overweight
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.