期刊
JOURNAL OF CLINICAL PHARMACOLOGY
卷 54, 期 2, 页码 121-132出版社
WILEY
DOI: 10.1002/jcph.167
关键词
infectious diseases (INF); pharmacokinetics and drug metabolism; pharmacodynamics (PDY); pharmacology (PHA); clinical research (CRE)
资金
- National Institute for Child Health and Human Development [P01 HD059454]
- President's Emergency Plan For AIDS Relief
- Office of the Global AIDS Coordinator
- Office of AIDS Research
- National Institute of Mental Health [K01 MH098902]
- CFAR, UCSF-GIVI Center for AIDS Research [P30 AI022763 NIH/NIAID]
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 20.2kg/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.
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