학술논문

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
Document Type
article
Source
Antimicrobial Agents and Chemotherapy. 59(4)
Subject
Medical Microbiology
Biomedical and Clinical Sciences
HIV/AIDS
Infectious Diseases
Clinical Research
Contraception/Reproduction
Sexually Transmitted Infections
Evaluation of treatments and therapeutic interventions
6.1 Pharmaceuticals
Infection
Good Health and Well Being
Adolescent
Contraceptives
Oral
Synthetic
Delayed-Action Preparations
Drug Interactions
Female
HIV Infections
HIV Protease Inhibitors
Humans
Lopinavir
Medroxyprogesterone Acetate
Middle Aged
Ovulation
Progesterone
Ritonavir
Young Adult
Microbiology
Pharmacology and Pharmaceutical Sciences
Medical microbiology
Pharmacology and pharmaceutical sciences
Language
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.).