Contraceptive Efficacy of Oral and Transdermal Hormones When Co-Administered With Protease Inhibitors in HIV-1-Infected Women: Pharmacokinetic Results of ACTG Trial A5188

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 AUC02168 h was 45% lower at 6010.36 pg.h.mL(-1) in those on LPV/r versus 10911.42 pg.h.mL(-1) in those on no HAART (P = 0.064). Pill EE median AUC(0-48) hours was similarly 55% lower at 344.67 pg.h.mL(-1) in those on LPV/r versus 765.38 pg.h.mL(-1) in those on no HAART (P = 0.003). Patch NGMN AUC(0-168) (h) however, was 138.39 ng.h.mL(-1), 83% higher in the LPV/r group compared with the control AUC of 75.63 ng.h.mL(-1) (P = 0.036). After 3 weeks on the patch, LPVAUC(0-8) (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.