Contraceptive efficacy of oral and transdermal hormones when co-administered with protease inhibitors in HIV-1-infected women: pharmacokinetic results of ACTG trial A5188.

TitleContraceptive efficacy of oral and transdermal hormones when co-administered with protease inhibitors in HIV-1-infected women: pharmacokinetic results of ACTG trial A5188.
Publication TypeJournal Article
Year of Publication2010
AuthorsVogler MA, Patterson K, Kamemoto L, Park J-G, Watts H, Aweeka F, Klingman KL, Cohn SE
JournalJ Acquir Immune Defic Syndr
Volume55
Issue4
Pagination473-82
Date Published2010 Dec
ISSN1944-7884
KeywordsAdolescent, Adult, Contraceptives, Oral, Combined, Drug Interactions, Estrogens, Ethinyl Estradiol, Female, HIV Infections, HIV Protease Inhibitors, HIV-1, Humans, Lopinavir, Middle Aged, Norgestrel, Oximes, Pyrimidinones, Ritonavir, Transdermal Patch, United States
Abstract

BACKGROUND: Pharmacokinetic (PK) interactions between lopinavir/ritonavir (LPV/r) and transdermally delivered ethinyl estradiol (EE) and norelgestromin (NGMN) are unknown.

METHODS: Using a standard noncompartmental PK analysis, we compared EE area under the time-concentration curve (AUC) and NGMN AUC during transdermal contraceptive patch administration in HIV-1-infected women on stable LPV/r to a control group of women not on highly active antiretroviral therapy (HAART). In addition, EE AUC after a single dose of a combination oral contraceptive pill including EE and norethindrone was measured before patch placement and was compared with patch EE AUC in both groups. Contraceptive effects on LPV/r PKs were estimated by measuring LPV/r AUC at baseline and during week 3 of patch administration.

RESULTS: Eight women on LPV/r, and 24 women in the control group were enrolled. Patch EE median AUC0-168 h was 45% lower at 6010.36 pg·h·mL in those on LPV/r versus 10911.42 pg·h·mL in those on no HAART (P = 0.064). Pill EE median AUC0-48 hours was similarly 55% lower at 344.67 pg·h·mL in those on LPV/r versus 765.38 pg·h·mL in those on no HAART (P = 0.003). Patch NGMN AUC0-168 h however, was 138.39 ng·h·mL, 83% higher in the LPV/r group compared with the control AUC of 75.63 ng·h·mL (P = 0.036). After 3 weeks on the patch, LPV AUC0-8 h decreased by 19%, (P = 0.156).

CONCLUSIONS: Although PKs of contraceptive EE and NGMN are significantly altered with LPV/r, the contraceptive efficacy of the patch is likely to be maintained. Larger studies are indicated to fully assess contraceptive efficacy versus risks of the transdermal contraceptive patch when co-administered with protease inhibitors.

DOI10.1097/QAI.0b013e3181eb5ff5
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID20842042
PubMed Central IDPMC4197050
Grant List1 U01 AI 069494-01 / AI / NIAID NIH HHS / United States
AI-69419 / AI / NIAID NIH HHS / United States
AI025859 / AI / NIAID NIH HHS / United States
AI054907 / AI / NIAID NIH HHS / United States
AI069428 / AI / NIAID NIH HHS / United States
AI46370 / AI / NIAID NIH HHS / United States
AI69415 / AI / NIAID NIH HHS / United States
M01 RR000043 / RR / NCRR NIH HHS / United States
M01 RR000043-47 / RR / NCRR NIH HHS / United States
M0IRR00043 / / PHS HHS / United States
N01 HD033345 / HD / NICHD NIH HHS / United States
N01-HD-8-0001 / HD / NICHD NIH HHS / United States
N01HD33345 / HD / NICHD NIH HHS / United States
P30 AI054907 / AI / NIAID NIH HHS / United States
P30 AI054907-01 / AI / NIAID NIH HHS / United States
RR024996 / RR / NCRR NIH HHS / United States
RR025780 / RR / NCRR NIH HHS / United States
U01 AI025859-16 / AI / NIAID NIH HHS / United States
U01 AI046370-01 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI068636-01 / AI / NIAID NIH HHS / United States
U01 AI069415-06 / AI / NIAID NIH HHS / United States
U01 AI069419 / AI / NIAID NIH HHS / United States
U01 AI069419-01 / AI / NIAID NIH HHS / United States
U01 AI069428 / AI / NIAID NIH HHS / United States
U01 AI069428-06 / AI / NIAID NIH HHS / United States
U01 AI069494 / AI / NIAID NIH HHS / United States
U01 AI069494-01 / AI / NIAID NIH HHS / United States
UL1 RR024996 / RR / NCRR NIH HHS / United States
UL1 RR024996-01 / RR / NCRR NIH HHS / United States
UL1 RR025780 / RR / NCRR NIH HHS / United States
UL1 RR025780-01 / RR / NCRR NIH HHS / United States