Depot medroxyprogesterone acetate in combination with a twice-daily lopinavir-ritonavir-based regimen in HIV-infected women showed effective contraception and a lack of clinically significant interactions, with good safety and tolerability: results of the ACTG 5283 study

Antimicrob Agents Chemother. 2015 Apr;59(4):2094-101. doi: 10.1128/AAC.04701-14. Epub 2015 Jan 26.

Abstract

We conducted an open-label, steady-state pharmacokinetic (PK) study of drug-drug interactions between depot medroxyprogesterone acetate (DMPA) and twice-daily lopinavir (LPV) plus low-dose ritonavir (RTV) (LPV/r) among 24 HIV-infected women and compared the results to those for HIV-infected women receiving DMPA while on no antiretroviral therapy or on nucleosides only (n = 14 subjects from the control arm of AIDS Clinical Trials Group [ACTG] study 5093). The objectives of the study were to address the effect of LPV/r on DMPA and to address the effect of DMPA on LPV/r therapy. PK parameters were estimated using noncompartmental analysis with between-group comparisons of medroxyprogesterone acetate (MPA) PKs and within-subject comparisons of LPV and RTV PKs before and 4 weeks after DMPA dosing. Plasma progesterone concentrations were measured every 2 weeks after DMPA dosing through week 12. Although the MPA area under the concentration-time curve and maximum concentration of drug in plasma were statistically significantly increased in the study women on LPV/r compared to those in the historical controls, these increases were not considered clinically significant. There were no changes in LPV or RTV exposure after DMPA. DMPA was well tolerated, and suppression of ovulation was maintained. (This study has been registered at ClinicalTrials.gov under registration no. NCT01296152.).

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Contraceptives, Oral, Synthetic / adverse effects*
  • Contraceptives, Oral, Synthetic / pharmacology*
  • Delayed-Action Preparations
  • Drug Interactions
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease Inhibitors / adverse effects*
  • HIV Protease Inhibitors / pharmacokinetics
  • HIV Protease Inhibitors / therapeutic use*
  • Humans
  • Lopinavir / adverse effects*
  • Lopinavir / pharmacokinetics
  • Lopinavir / therapeutic use*
  • Medroxyprogesterone Acetate / adverse effects*
  • Medroxyprogesterone Acetate / pharmacology*
  • Middle Aged
  • Ovulation / drug effects
  • Progesterone / blood
  • Ritonavir / adverse effects*
  • Ritonavir / pharmacokinetics
  • Ritonavir / therapeutic use*
  • Young Adult

Substances

  • Contraceptives, Oral, Synthetic
  • Delayed-Action Preparations
  • HIV Protease Inhibitors
  • Lopinavir
  • Progesterone
  • Medroxyprogesterone Acetate
  • Ritonavir

Associated data

  • ClinicalTrials.gov/NCT01296152

Grants and funding