Clinical trial NCT01903031
Conditions: HIV-1 Infection
Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Start date: 2014-12-30; Completion date: 2016-10-10
Enrollment: 84 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study was done to look at a method of hormonal birth control, called the NuvaRing, and specific anti-HIV medications, called antiretrovirals (ARVs). Some studies of women who use a hormonal birth control method (specifically oral pills, patches, and injections) and take ARVs have shown that ARVs interact with the hormones released by the birth control medication. These interactions may cause the birth control to be less effective at preventing pregnancy. There is also concern that hormonal birth control can increase HIV spreading to others, but more studies are needed to determine if this is true. The investigators did not know whether the NuvaRing and ARVs interact when they are used together, so this study looked to see if certain ARVs (efavirenz and atazanavir/ritonavir) interact with the two hormones released by NuvaRing. This will help us to determine if NuvaRing is safe and effective for women with HIV infection who are taking ARVs. The study also included HIV-infected women who were not on ARVs but used the NuvaRing to show us what the hormone levels are like in a similar group of women not on ARVs.

Vaginal rings are also currently being studied to deliver anti-HIV medications that may prevent HIV acquisition, and to provide birth control over a longer period of time (more than 1 month). Since vaginal rings will become more commonly used to administer medications, the investigators wanted to better understand the potential for drug interactions with drugs given vaginally. This study will also help us understand the potential for drug interactions between ARVs given orally, and other drugs given through vaginal rings, like the NuvaRing. Additionally, this study will help us understand how hormones released from a vaginal ring affect the amount of HIV virus in the genital tract, the bacterial make-up (microbiome) of the female genital tract, and the immune system within the genital tract, all of which may affect the chances of spreading HIV.

Detailed description:
This was a 28 day study from study entry through the final clinic visit. Post-entry visits were scheduled at Days 7, 14, 21 and 28. The Nuvaring was put in place at study entry and removed on day 21. A single pharmacokinetic (PK) blood sample was collected for assay of etonogestrel (ENG) and ethinyl estradiol (EE) at entry (day 0, prior to NuvaRing placement), and on days 7, 14, and 21 after placement of the NuvaRing. For participants on the ARV arms, intensive, 8-hour PK sampling, for assay of efavirenz (EFV) and atazanavir/ritonavir (ATV/RTV) respectively, was performed at study entry (day 0, prior to NuvaRing placement) and 21 days later. ARV sampling was performed at pre-dose (hour 0), and 1, 3, 4, 5, and 8 hours post-dose. Safety was assessed at each study visit.

Arms: arm 1: Once NuvaRing is inserted into the vagina, the ring should remain in place (not be removed) continuously for 3 weeks (21 days). arm 2: Once NuvaRing is inserted into the vagina, the ring should remain in place (not be removed) continuously for 3 weeks (21 days). EFV is a non-nucleoside reverse transcriptase inhibitor taken at a dose of 600 mg once daily. arm 3: Once NuvaRing is inserted into the vagina, the ring should remain in place (not be removed) continuously for 3 weeks (21 days). ATV/r is a combination protease inhibitor taken at a dose of 300/100 mg once daily. Tenofovir disoproxil fumarate (TDF) is a nucleoside reverse transcriptase inhibitor (NRTI) taken at a dose of 300 mg daily.
Interventions: intervention 1: Nuvaring intervention 2: EFV intervention 3: ATV/r intervention 4: TDF intervention 5: NRTIs
Intervention descriptions: intervention 1: NuvaRing is made of ethylene vinylacetate copolymers (28% and 9% vinylacetate) and magnesium stearate, is latex free, and contains 11.7 mg etonogestrel and 2.7 mg ethinyl estradiol. NuvaRing has an outer diameter of 54 mm and a cross-sectional diameter of 4mm. Once NuvaRing is inserted into the vagina, the ring should remain in place (not be removed) continuously for 3 weeks (21 days). After being in place for the first 21 days of the study, the ring may be removed after the day 21 study visit evaluations have been completed. intervention 2: Participants received EFV 600 mg daily with two or more NRTIs intervention 3: Participants received ATV/r 300 mg/ 100 mg daily with tenofovir and one or more additional NRTIs intervention 4: Participants received 300 mg of tenofovir in Arm C intervention 5: Participants received two or more NRTIs in Arm B and one or more NRTIs in Arm C

Protocol documents: