Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate versus Ethinylestradiol/Levonorgestrel
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Study Design
PK substudy in an open label extension of a Phase 3 randomized, blinded study in HIV-infected treatment-naïve women that evaluated safety and efficacy of EVG(150 mg) /COBI(150 mg)/FTC(200 mg)/TDF(300 mg) versus ritonavir(100 mg)-boosted ATV(300mg) +FTC(200 mg)/TDF(300 mg). In a subset of consenting subjects not on OCs (n=25) receiving EVG/COBI/FTC/TDF, an OC regimen was administered according to local practice and per investigator’s discretion (levonorgestrel/EE; n=20, norgestimate/EE; n=1, drospirenone/EE; n=4) for 7 days and intensive PK sampling was performed. PK parameters of OCs (norgestrel and EE) were compared to historical data. Safety was assessed throughout the studies.
Study Results
coadministration of OCs with EVG/COBI/FTC/TDF in HIV-infected women resulted in norgestrel AUC and Cmax that were 2-fold and 1.6-fold higher, respectively, compared to historical data of levonorgestrel/EE administered alone, while EE exposures were consistent with those reported when levonorgestrel/EE was administered alone. All subjects completed the substudy and all treatments were generally well tolerated.
Study Conclusions
The authors concluded that the increase in progestin (norgestrel) levels was consistent with known CYP3A inhibition by cobicistat. Further, the decrease in EE exposure has been seen in previous drug interaction studies utilizing OCs with darunavir+ritonavir. The findings in this study were expected and such align with the prescribing recommendations for combining these agents.
References
Majeed S, West S, Jiang S, Andrews J, Sinha S, Ling K. Confirmation of the drug-drug interaction (ddi) potential between cobicistat-boosted antiretroviral regimens and hormonal contraceptives. International Workshop On Clinical Pharmacology Of Antiviral Therapy. Chicago, IL, USA. 18; June 2017.
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