title: 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.
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.).
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, New York, USA amneris_luque@urmc.rochester.edu.
authors.forename: Amneris E
authors.initials: AE
authors.lastname: Luque
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Cohn
authors.affiliation: Statistical and Data Analysis Center, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Jeong-Gun
authors.initials: JG
authors.lastname: Park
authors.affiliation: Statistical and Data Analysis Center, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Yoninah
authors.initials: Y
authors.lastname: Cramer
authors.affiliation: University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Weinberg
authors.affiliation: Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Livingston
authors.affiliation: Division of AIDS, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Karin L
authors.initials: KL
authors.lastname: Klingman
authors.affiliation: University of California, San Francisco, California, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Aweeka
authors.affiliation: Office of the Global AIDS Coordinator, U.S. Department of State, Washington, DC, USA.
authors.forename: D Heather
authors.initials: DH
authors.lastname: Watts
mesh_terms: D000293:Adolescent; D003280:Contraceptives, Oral, Synthetic / Q000009:adverse effects* / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D061466:Lopinavir / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects* / Q000494:pharmacology*; D008875:Middle Aged; D010060:Ovulation / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D019438:Ritonavir / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D003280:Contraceptives, Oral, Synthetic; D003692:Delayed-Action Preparations; D017320:HIV Protease Inhibitors; D061466:Lopinavir; D011374:Progesterone; D017258:Medroxyprogesterone Acetate; D019438:Ritonavir