TY - JOUR
T1 - Pharmacokinetics of lopinavir/ritonavir and efavirenz in food insecure HIV-infected pregnant and breastfeeding women in Tororo, Uganda
AU - Bartelink, Imke H.
AU - Savic, Rada M.
AU - Mwesigwa, Julia
AU - Achan, Jane
AU - Clark, Tamara
AU - Plenty, Albert
AU - Charlebois, Edwin
AU - Kamya, Moses
AU - Young, Sera L.
AU - Gandhi, Monica
AU - Havlir, Diane
AU - Cohan, Deborah
AU - Aweeka, Francesca
PY - 2014/2
Y1 - 2014/2
N2 - Pregnancy and food insecurity may impact antiretroviral (ART) pharmacokinetics (PK), adherence and response.Wesought 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.
AB - Pregnancy and food insecurity may impact antiretroviral (ART) pharmacokinetics (PK), adherence and response.Wesought 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.
KW - Clinical research (CRE)
KW - Infectious diseases (INF)
KW - Pharmacodynamics (PDY)
KW - Pharmacokinetics and drug metabolism
KW - Pharmacology (PHA)
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U2 - 10.1002/jcph.167
DO - 10.1002/jcph.167
M3 - Article
C2 - 24038035
AN - SCOPUS:84895758293
SN - 0091-2700
VL - 54
SP - 121
EP - 132
JO - Journal of Clinical Pharmacology
JF - Journal of Clinical Pharmacology
IS - 2
ER -
