title: Pharmacokinetics of lopinavir/ritonavir and efavirenz in food insecure HIV-infected pregnant and breastfeeding women in Tororo, Uganda.
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/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.
authors.affiliation: Department of Clinical Pharmacy, Drug Research Unit, University of California, San Francisco, CA, USA.
authors.forename: Imke H
authors.initials: IH
authors.lastname: Bartelink
authors.forename: Rada M
authors.initials: RM
authors.lastname: Savic
authors.forename: Julia
authors.initials: J
authors.lastname: Mwesigwa
authors.forename: Jane
authors.initials: J
authors.lastname: Achan
authors.forename: Tamara
authors.initials: T
authors.lastname: Clark
authors.forename: Albert
authors.initials: A
authors.lastname: Plenty
authors.forename: Edwin
authors.initials: E
authors.lastname: Charlebois
authors.forename: Moses
authors.initials: M
authors.lastname: Kamya
authors.forename: Sera L
authors.initials: SL
authors.lastname: Young
authors.forename: Monica
authors.initials: M
authors.lastname: Gandhi
authors.forename: Diane
authors.initials: D
authors.lastname: Havlir
authors.forename: Deborah
authors.initials: D
authors.lastname: Cohan
authors.forename: Francesca
authors.initials: F
authors.lastname: Aweeka
mesh_terms: D000293:Adolescent; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000493:pharmacokinetics; D048588:Benzoxazines / Q000493:pharmacokinetics*; D001682:Biological Availability; D001942:Breast Feeding; D003521:Cyclopropanes; D059788:Dried Blood Spot Testing; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000378:metabolism* / Q000523:psychology; D006197:Hair / Q000378:metabolism; D006801:Humans; D061466:Lopinavir / Q000097:blood / Q000493:pharmacokinetics*; D044342:Malnutrition / Q000097:blood*; D055118:Medication Adherence / Q000523:psychology; D008875:Middle Aged; D009752:Nutritional Status; D049590:Postpartum Period / Q000097:blood; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D019438:Ritonavir / Q000097:blood / Q000493:pharmacokinetics*; D014454:Uganda; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D004338:Drug Combinations; D061466:Lopinavir; C098320:efavirenz; D019438:Ritonavir
keywords: clinical research (CRE); infectious diseases (INF); pharmacodynamics (PDY); pharmacokinetics and drug metabolism; pharmacology (PHA)
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