Pharmacokinetics of lopinavir/ritonavir and efavirenz in food insecure HIV-infected pregnant and breastfeeding women in Tororo, Uganda

J Clin Pharmacol. 2014 Feb;54(2):121-32. doi: 10.1002/jcph.167. Epub 2013 Sep 21.


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.

Keywords: clinical research (CRE); infectious diseases (INF); pharmacodynamics (PDY); pharmacokinetics and drug metabolism; pharmacology (PHA).

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Alkynes
  • Anti-HIV Agents / pharmacokinetics
  • Benzoxazines / pharmacokinetics*
  • Biological Availability
  • Breast Feeding*
  • Cyclopropanes
  • Dried Blood Spot Testing
  • Drug Combinations
  • Drug Therapy, Combination
  • Female
  • HIV Infections / metabolism*
  • HIV Infections / psychology
  • Hair / metabolism
  • Humans
  • Lopinavir / blood
  • Lopinavir / pharmacokinetics*
  • Malnutrition / blood*
  • Medication Adherence / psychology
  • Middle Aged
  • Nutritional Status*
  • Postpartum Period / blood
  • Pregnancy
  • Pregnancy Complications, Infectious
  • Ritonavir / blood
  • Ritonavir / pharmacokinetics*
  • Uganda
  • Young Adult


  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Drug Combinations
  • Lopinavir
  • efavirenz
  • Ritonavir