CompletedNCT01903031Updated Jun 6, 2018Results posted

Evaluating Pharmacokinetic Interactions With Vaginal Ring Contraceptives and ART

A Phase 2 interventional study of Nuvaring and EFV in HIV-1 Infection, sponsored by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections. Completed at 21 sites in 8 countries. Open to female participants aged 16 Years and older. Per ClinicalTrials.gov, last updated 2018-06-06.

Sponsored by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 84
Allocation: Non-randomized
Ages: 16 Years and older
Sex: Female

Study 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.

Read the 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.

Conditions studied

HIV-1 Infection

In context

Lead sponsor

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections is the lead sponsor of 70 studies on the registry; 3 are open to participants now.

Of its 7 completed or terminated interventional studies of FDA-regulated products, 6 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 16 Years and older
Sexes eligible: Female
Accepts healthy volunteers: No

Inclusion criteria

Documented HIV-1 infection.
Participants must have been receiving either 1) EFV 600 mg daily with 2 or more NRTIs, 2) ATV/r 300 mg/ 100 mg daily with TDF 300 mg and 1 or more additional NRTIs, or 3) no ART. ART regimens should have been stable for 30 days prior to study entry with no plans to change therapy during the first 28 days of this study. Participants receiving no ART should have had no plans to initiate ART during the first 28 days of the study.

NOTE: Participants must have had access to their ART regimens through their primary care providers. ART medications were not supplied by this study.

For participants on ART, documentation of plasma HIV-1 RNA ≤400 copies/mL was obtained within 60 days prior to study entry.
For participants not on ART, CD4+ cell count must have been ≥350 cells/mm\^3, obtained within 60 days prior to study entry.
Laboratory values within 60 days prior to study entry:
- Platelet count ≥50,000 platelets/mm\^3
- Hemoglobin ≥8.0 g/dL
- Aspartate transaminase (SGOT) and alanine aminotransferase (SGPT) \<5 x upper limit of normal (ULN)
- Creatinine ≤1.5 x ULN
- Total bilirubin ≤2.0 x ULN
Last menstrual period ≤6 months prior to study entry. If last menstrual period >6 months prior to study entry without another cause for amenorrhea, such as recent pregnancy, serum follicle-stimulating hormone (FSH) must have been checked and be ≤40 mIU/mL to be eligible for enrollment.
Premenopausal females with at least one functioning ovary.
Documentation of Pap smear within 1 year prior to study entry.
Negative serum or urine-HCG pregnancy test with a sensitivity of ≤25 mIU/mL within 60 days prior to study entry and within 24 hours prior to study entry
All participants must have agreed not to participate in a conception process (eg, active attempt to become pregnant or in vitro fertilization) for the duration of the study. Because it was unknown if ARVs adversely affect the efficacy of NuvaRing as a contraceptive method, participants of reproductive potential, who were participating in sexual activities that could lead to pregnancy, must have agreed to use an additional reliable form of contraception while in the study. Acceptable additional methods of contraception included:
- Condoms (male or female)
- Non-hormonal intrauterine device (IUD)

Other hormonal forms of contraception were not allowed during the study period.

Condoms should have been used to prevent transmission of HIV and sexually transmitted diseases between sexual partners.

NOTE: Participants with bilateral tubal ligation or non-hormonal IUD were eligible to be enrolled.

Exclusion criteria

Exclusion Criteria:

Received depot medroxyprogesterone acetate (DMPA) within 4 months prior to study entry.
Received other hormonal therapies (eg, oral contraceptive agents, hormone- containing vaginal ring, contraceptive patch, hormone replacement therapy, anabolic therapies, including nandrolone decanoate or megestrol acetate) within 30 days prior to study entry.
Breastfeeding.
Less than 6 weeks postpartum at study entry.
Use of any prohibited medications within 30 days prior to study entry.
Initiated, discontinued, or changed doses of drugs that are CYP substrates or known to have drug interactions with ethinyl estradiol or etonogestrel within 30 days prior to study entry.
Bilateral oophorectomy.
For women older than 35 years of age, smoking 15 or more cigarettes per day.
History of invasive cancer of the reproductive tract; known or suspected malignancy of the breast, or known increased risk for breast cancer; undiagnosed abnormal vaginal bleeding; liver tumors; or serious ocular disorders at any time prior to study entry.
Chronic immunosuppressive conditions other than HIV.
Use of systemic or inhaled corticosteroids such as for acute therapy for Pneumocystis pneumonia (PCP) or asthma exacerbation and prednisone ≥10 mg (or equivalent) for any reason other than a stable or tapering dose.
History of deep venous thrombosis or pulmonary embolism.
History of cerebral vascular or coronary artery disease.
Severe uncontrolled hypertension within 60 days prior to study entry.
Diabetes with vascular involvement.
Clinically active cervical or vaginal infection at study entry. NOTE: Gonorrhea, chlamydia, and trichomonas testing was performed during screening using techniques available at the local sites and documented in source documentation and case report forms (CRFs). Testing for bacterial vaginosis, performed using techniques available at the local sites, was only necessary if the participant was symptomatic and the provider felt treatment might be necessary. Women with genital herpes lesions waited to be screened until the herpetic lesions had healed.
Acute infections or other opportunistic diseases requiring medication within 14 days prior to study entry.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 84 participants (actual)

Study arms

Experimental
NuvaRing and no ART (Arm A)
Once NuvaRing is inserted into the vagina, the ring should remain in place (not be removed) continuously for 3 weeks (21 days).
Device: Nuvaring
Experimental
NuvaRing with EFV plus ≥2 NRTIs (Arm B)
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.
Device: Nuvaring · Drug: EFV · Drug: NRTIs
Experimental
NuvaRing with ATV/r plus TDF + ≥1 NRTIs (Arm C)
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.
Device: Nuvaring · Drug: ATV/r · Drug: TDF · Drug: NRTIs

Interventions

DeviceNuvaring
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.
Also known as: Etonogestrel/ethinyl estradiol vaginal ring
DrugEFV
Participants received EFV 600 mg daily with two or more NRTIs
Also known as: Efavirenz
DrugATV/r
Participants received ATV/r 300 mg/ 100 mg daily with tenofovir and one or more additional NRTIs
Also known as: Atazanavir/Ritonavir
DrugTDF
Participants received 300 mg of tenofovir in Arm C
Also known as: Tenofovir Disoproxil Fumarate
DrugNRTIs
Participants received two or more NRTIs in Arm B and one or more NRTIs in Arm C
Also known as: Nucleoside Reverse Transcriptase Inhibitor

What researchers measure

Primary outcomes

Etonogestrel Concentrations at Study Day 21
This evaluates the effect of EFV and ATV/r on etonogestrel by measuring etonogestrel concentrations on all three study arms 21 days after NuvaRing administration. The pharmacokinetic (PK) blood sample for measurement of etonogestrel on study day 21 was taken before the NuvaRing was removed. The assay lower limit of quantification for etonogestrel was 250 pg/mL; values \< 250 were assigned a value of half the lower limit (ie, 125 pg/mL).
Time frame: Day 21
Ethinyl Estradiol Concentrations at Study Day 21
This evaluates the effect of EFV and ATV/r on ethinyl estradiol by measuring ethinyl estradiol concentrations on all three study arms 21 days after NuvaRing administration. The PK blood sample for measurement of ethinyl estradiol on study day 21 was taken before the NuvaRing was removed. The assay lower limit of quantification for ethinyl estradiol was 5 pg/mL ; values \< 5 were assigned a value of half the lower limit (ie, 2.5 pg/mL).
Time frame: Day 21

Secondary outcomes

Etonogestrel Concentrations Obtained on Study Days 7 and 14
This evaluates the effect of EFV and ATV/r on etonogestrel by measuring etonogestrel concentrations on all three study arms 7 and 14 days after NuvaRing administration. The assay lower limit of quantification for etonogestrel was 250 pg/mL; values \< 250 were assigned a value of half the lower limit (ie, 125 pg/mL).
Time frame: Study days 7 and 14
Ethinyl Estradiol Concentrations Obtained on Study Days 7 and 14.
This evaluates the effect of EFV and ATV/r on ethinyl estradiol by measuring ethinyl estradiol concentrations on all three study arms 7 and 14 days after NuvaRing administration. The assay lower limit of quantification for ethinyl estradiol was 5 pg/mL; values \< 5 were assigned a value of half the lower limit (ie, 2.5 pg/mL).
Time frame: Study days 7 and 14
EFV PK Parameter Area Under the Concentration-Time Curve (AUC0-24hours) Calculated Based on Intensive EFV PK Samples Obtained From Individual Participants Enrolled in Arm B
This evaluates the effect of NuvaRing on the PK parameter AUC(0-24h) of EFV before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. AUC(0-24h) defines area under the concentration-time curve over the period of 24 hours (pre-dose concentration was used to impute concentration at 24h).
Time frame: Intensive EFV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement).
EFV PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B
This evaluates the effect of NuvaRing on the EFV PK parameter Cmin obtained from both sampling periods, before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. Cmin defines minimum concentration observed within the first 8 hours of the 24 hour dosing interval.
Time frame: Intensive EFV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement).
EFV PK Parameter Maximum Plasma Concentration (Cmax) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B
This evaluates the effect of NuvaRing on the EFV PK parameter Cmax obtained from both sampling periods, before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. Cmax defines maximum concentration observed within the first 8 hours of the 24 hour dosing interval.
Time frame: Intensive EFV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement).
EFV PK Parameter Clearance (CLss/F) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B
This evaluates the effect of NuvaRing on the EFV PK parameter CLss/F obtained from both sampling periods, before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. CLss/F defines apparent oral clearance
Time frame: Intensive EFV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement).
ATV PK Parameter AUC(0-24h) Calculated Based on Intensive Atazanavir (ATV) PK Samples Obtained From Individual Participants Enrolled in Arm C
This evaluates the effect of NuvaRing on the PK parameter AUC(0-24h) of ATV before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. AUC(0-24h) defines area under the concentration-time curve over the period of 24 hours (pre-dose concentration was used to impute concentration at 24h).
Time frame: Intensive ATV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement)
ATV PK Parameter Cmin Determined Based on ATV Levels From Individual Participants Enrolled in Arm C
This evaluates the effect of NuvaRing on the ATV PK parameter Cmin obtained from both sampling periods, before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. Cmin defines minimum concentration observed within the first 8 hours of the 24 hour dosing interval.
Time frame: Intensive ATV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement).
ATV PK Parameter Cmax Determined Based on ATV Levels From Individual Participants Enrolled in Arm C
This evaluates the effect of NuvaRing on the ATV PK parameter Cmax obtained from both sampling periods, before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. Cmax defines maximum concentration observed within the first 8 hours of the 24 hour dosing interval.
Time frame: Intensive ATV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement).
ATV PK Parameter Time to Cmax (Tmax) Determined Based on ATV Levels From Individual Participants Enrolled in Arm C
This evaluates the effect of NuvaRing on the ATV PK parameter Tmax obtained from both sampling periods, before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. Tmax defines time to maximum concentration since dose is initiated.
Time frame: Intensive ATV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement).
ATV PK Parameter CLss/F Determined Based on ATV Levels From Individual Participants Enrolled in Arm C
This evaluates the effect of NuvaRing on the ATV PK parameter CLss/F obtained from both sampling periods, before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. CLss/f defines apparent oral clearance.
Time frame: Intensive ATV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement).
Ritonavir (RTV) PK Parameter AUC(0-24h) Calculated Based on Intensive RTV PK Samples Obtained From Individual Participants Enrolled in Arm C
This evaluates the effect of NuvaRing on the PK parameter AUC(0-24h) of RTV before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. AUC(0-24h) defines area under the concentration-time curve over the period of 24 hours (pre-dose concentration was used to impute concentration at 24h).
Time frame: Intensive RTV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement)
RTV PK Parameter Cmin Determined Based on RTV Levels From Individual Participants Enrolled in Arm C
This evaluates the effect of NuvaRing on the PK parameter Cmin of RTV before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. Cmin defines minimum concentration observed within the first 8 hours of the 24 hour dosing interval.
Time frame: Intensive RTV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement)
RTV PK Parameter Cmax Determined Based on RTV Levels From Individual Participants Enrolled in Arm C
This evaluates the effect of NuvaRing on the PK parameter Cmax of RTV before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. Cmax defines maximum concentration observed within the first 8 hours of the 24 hour dosing interval.
Time frame: Intensive RTV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement)
RTV PK Parameter Tmax Determined Based on RTV Levels From Individual Participants Enrolled in Arm C
This evaluates the effect of NuvaRing on the PK parameter Tmax of RTV before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. Tmax defines time to maximum concentration since dose is initiated.
Time frame: Intensive RTV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement)
RTV PK Parameter CLss/F Determined Based on RTV Levels From Individual Participants Enrolled in Arm C
This evaluates the effect of NuvaRing on the PK parameter CLss/F of RTV before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. CLss/F defines apparent oral clearance.
Time frame: Intensive RTV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement)
Proportion of Participants With Plasma HIV-1 RNA Levels <40 Copies/mL
This evaluates the short-term impact of Nuvaring on virologic suppression in participants who have been administered Nuvaring alone or together with EFV or ATV/r by measuring proportion of participants with plasma HIV-1 RNA levels \<40 copies/mL at study day 0 (before vaginal ring placement) and study day 21 (three weeks after vaginal ring placement). An FDA-approved HIV-1 RNA assay was required.
Time frame: Study day 0 and study day 21
Percentage of Participants With Signs and Symptoms of Grade 2 or Higher Deemed Possibly, Probably or Definitely Related to Study Treatment
This evaluates toxicity and safety of NuvaRing alone, NuvaRing with EFV, and NuvaRing with ATV/r. Signs/symptoms were graded using the DAIDS AE Grading Table was used. Participants with sign(s)/symptom(s) of grade 2 (moderate), 3 (severe), 4 (potentially life-threatening) or 5 (death) are included in the percentage. Relationship to study treatment was determined by the study co-chairs and DAIDS clinical representative.
Time frame: From day 0 to day 28
Proportion of Participants With Progesterone Levels Greater Than 5 ng/mL.
This evaluates alterations in progesterone levels due to the potential PK interaction between NuvaRing and the ARVs EFV and ATV/r by examining progesterone levels at study days 0 (before vaginal ring placement), 7, 14, and 21 (before vaginal ring removal), and study day 28, without regard to menstrual cycle status at study entry.
Time frame: Study days 0, 7, 14, 21 and 28

Results

Posted Jan 4, 2018

Participant flow

The first participant enrolled in December 2014 and final participant enrolled in September 2016. Enrollment took place at 21 US and non-US clinical research sites.

Participant flow — Overall Study
Milestone	NuvaRing and no ART	NuvaRing With EFV Plus ≥2 NRTIs	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
Started	27	28	29
Completed	25	25	24
Not completed	2	3	5
Withdrew: Not able to attend clinic	1	1	0
Withdrew: Missed day 21 primary endpoint visit	1	0	0
Withdrew: Adverse event	0	1	0
Withdrew: Withdrawal by subject	0	1	1
Withdrew: Protocol violation	0	0	2
Withdrew: Lost to follow-up	0	0	1
Withdrew: Nuvaring removed prior to day 21 visit	0	0	1

Outcome measures

PrimaryEtonogestrel Concentrations at Study Day 21

This evaluates the effect of EFV and ATV/r on etonogestrel by measuring etonogestrel concentrations on all three study arms 21 days after NuvaRing administration. The pharmacokinetic (PK) blood sample for measurement of etonogestrel on study day 21 was taken before the NuvaRing was removed. The assay lower limit of quantification for etonogestrel was 250 pg/mL; values \< 250 were assigned a value of half the lower limit (ie, 125 pg/mL).

Time frame:: Day 21
Reported as:: Median · pg/mL

Etonogestrel Concentrations at Study Day 21
pg/mL	NuvaRing and no ART	NuvaRing With EFV Plus ≥2 NRTIs	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
Etonogestrel Concentrations at Study Day 21	1860.00 (665.00 to 3590.00)	429.00 (125.00 to 1180.00)	3290.00 (730.00 to 6920.00)

Statistical analysis

NuvaRing and no ART vs NuvaRing With EFV Plus ≥2 NRTIs · Wilcoxon (Mann-Whitney) · p = <0.001 (No adjustments for multiple comparisons were made. Statistical significance was declared if p\<0.05.)
NuvaRing and no ART vs NuvaRing With ATV/r Plus TDF and ≥1 NRTIs · Wilcoxon (Mann-Whitney) · p = <0.001 (No adjustments for multiple comparisons were made. Statistical significance was declared if p\<0.05.)

PrimaryEthinyl Estradiol Concentrations at Study Day 21

This evaluates the effect of EFV and ATV/r on ethinyl estradiol by measuring ethinyl estradiol concentrations on all three study arms 21 days after NuvaRing administration. The PK blood sample for measurement of ethinyl estradiol on study day 21 was taken before the NuvaRing was removed. The assay lower limit of quantification for ethinyl estradiol was 5 pg/mL ; values \< 5 were assigned a value of half the lower limit (ie, 2.5 pg/mL).

Time frame:: Day 21
Reported as:: Median · pg/mL

Ethinyl Estradiol Concentrations at Study Day 21
pg/mL	NuvaRing and no ART	NuvaRing With EFV Plus ≥2 NRTIs	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
Ethinyl Estradiol Concentrations at Study Day 21	21.30 (6.46 to 51.00)	11.40 (2.50 to 21.00)	16.05 (2.50 to 26.40)

Statistical analysis

NuvaRing and no ART vs NuvaRing With EFV Plus ≥2 NRTIs · Wilcoxon (Mann-Whitney) · p = <0.001 (No adjustments for multiple comparisons were made. Statistical significance was declared if p\<0.05.)
NuvaRing and no ART vs NuvaRing With ATV/r Plus TDF and ≥1 NRTIs · Wilcoxon (Mann-Whitney) · p = 0.004 (No adjustments for multiple comparisons were made. Statistical significance was declared if p\<0.05.)

SecondaryEtonogestrel Concentrations Obtained on Study Days 7 and 14

This evaluates the effect of EFV and ATV/r on etonogestrel by measuring etonogestrel concentrations on all three study arms 7 and 14 days after NuvaRing administration. The assay lower limit of quantification for etonogestrel was 250 pg/mL; values \< 250 were assigned a value of half the lower limit (ie, 125 pg/mL).

Time frame:: Study days 7 and 14
Reported as:: Median · pg/mL

Etonogestrel Concentrations Obtained on Study Days 7 and 14
pg/mL	NuvaRing and no ART	NuvaRing With EFV Plus ≥2 NRTIs	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
Concentration at Day 7	1970.00 (703.00 to 3220.00)	427.00 (125.00 to 916.00)	3250.00 (1330.00 to 4960.00)
Concentration at Day 14	2070.00 (648.00 to 3720.00)	437.00 (125.00 to 1090.00)	3530.00 (725.00 to 6100.00)

SecondaryEthinyl Estradiol Concentrations Obtained on Study Days 7 and 14.

This evaluates the effect of EFV and ATV/r on ethinyl estradiol by measuring ethinyl estradiol concentrations on all three study arms 7 and 14 days after NuvaRing administration. The assay lower limit of quantification for ethinyl estradiol was 5 pg/mL; values \< 5 were assigned a value of half the lower limit (ie, 2.5 pg/mL).

Time frame:: Study days 7 and 14
Reported as:: Median · pg/mL

Ethinyl Estradiol Concentrations Obtained on Study Days 7 and 14.
pg/mL	NuvaRing and no ART	NuvaRing With EFV Plus ≥2 NRTIs	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
Concentration at Day 7	18.05 (6.71 to 50.90)	9.98 (2.50 to 18.70)	15.70 (5.48 to 24.30)
Concentration at Day 14	19.70 (6.51 to 47.90)	10.50 (2.50 to 18.60)	16.55 (6.76 to 26.90)

SecondaryEFV PK Parameter Area Under the Concentration-Time Curve (AUC0-24hours) Calculated Based on Intensive EFV PK Samples Obtained From Individual Participants Enrolled in Arm B

This evaluates the effect of NuvaRing on the PK parameter AUC(0-24h) of EFV before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. AUC(0-24h) defines area under the concentration-time curve over the period of 24 hours (pre-dose concentration was used to impute concentration at 24h).

Time frame:: Intensive EFV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement).
Reported as:: Median · h*ng/mL

EFV PK Parameter Area Under the Concentration-Time Curve (AUC0-24hours) Calculated Based on Intensive EFV PK Samples Obtained From Individual Participants Enrolled in Arm B
h*ng/mL	NuvaRing With EFV Plus ≥2 NRTIs
AUC0-24h day 0	68949.1 (27114.3 to 367995.4)
AUC0-24h day 21	57795.9 (26326.3 to 362821.3)

SecondaryEFV PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B

This evaluates the effect of NuvaRing on the EFV PK parameter Cmin obtained from both sampling periods, before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. Cmin defines minimum concentration observed within the first 8 hours of the 24 hour dosing interval.

Time frame:: Intensive EFV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement).
Reported as:: Median · ng/mL

EFV PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B
ng/mL	NuvaRing With EFV Plus ≥2 NRTIs
Cmin day 0	2121.5 (903.7 to 13620.0)
Cmin day 21	1766.0 (10.0 to 12930.0)

SecondaryEFV PK Parameter Maximum Plasma Concentration (Cmax) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B

This evaluates the effect of NuvaRing on the EFV PK parameter Cmax obtained from both sampling periods, before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. Cmax defines maximum concentration observed within the first 8 hours of the 24 hour dosing interval.

Time frame:: Intensive EFV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement).
Reported as:: Median · ng/mL

EFV PK Parameter Maximum Plasma Concentration (Cmax) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B
ng/mL	NuvaRing With EFV Plus ≥2 NRTIs
Cmax day 0	4541.0 (1347.0 to 18670.0)
Cmax day 21	3786.0 (2231.0 to 19110.0)

SecondaryEFV PK Parameter Clearance (CLss/F) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B

This evaluates the effect of NuvaRing on the EFV PK parameter CLss/F obtained from both sampling periods, before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. CLss/F defines apparent oral clearance

Time frame:: Intensive EFV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement).
Reported as:: Median · L/h

EFV PK Parameter Clearance (CLss/F) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B
L/h	NuvaRing With EFV Plus ≥2 NRTIs
CLss/F day 0	8.7 (1.6 to 22.1)
CLss/F day 21	10.4 (1.7 to 22.8)

SecondaryATV PK Parameter AUC(0-24h) Calculated Based on Intensive Atazanavir (ATV) PK Samples Obtained From Individual Participants Enrolled in Arm C

This evaluates the effect of NuvaRing on the PK parameter AUC(0-24h) of ATV before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. AUC(0-24h) defines area under the concentration-time curve over the period of 24 hours (pre-dose concentration was used to impute concentration at 24h).

Time frame:: Intensive ATV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement)
Reported as:: Median · h*ng/mL

ATV PK Parameter AUC(0-24h) Calculated Based on Intensive Atazanavir (ATV) PK Samples Obtained From Individual Participants Enrolled in Arm C
h*ng/mL	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
AUC0-24h day 0	44313.7 (8802.3 to 91766.5)
AUC0-24h day 21	36764.7 (1346.9 to 108450.6)

SecondaryATV PK Parameter Cmin Determined Based on ATV Levels From Individual Participants Enrolled in Arm C

This evaluates the effect of NuvaRing on the ATV PK parameter Cmin obtained from both sampling periods, before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. Cmin defines minimum concentration observed within the first 8 hours of the 24 hour dosing interval.

Time frame:: Intensive ATV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement).
Reported as:: Median · ng/mL

ATV PK Parameter Cmin Determined Based on ATV Levels From Individual Participants Enrolled in Arm C
ng/mL	NuvaRing With ATV/r Plus TDF ≥1 NRTIs
Cmin day 0	796.7 (10.0 to 2731.0)
Cmin day 21	599.4 (10.0 to 3599.0)

SecondaryATV PK Parameter Cmax Determined Based on ATV Levels From Individual Participants Enrolled in Arm C

This evaluates the effect of NuvaRing on the ATV PK parameter Cmax obtained from both sampling periods, before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. Cmax defines maximum concentration observed within the first 8 hours of the 24 hour dosing interval.

Time frame:: Intensive ATV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement).
Reported as:: Median · ng/mL

ATV PK Parameter Cmax Determined Based on ATV Levels From Individual Participants Enrolled in Arm C
ng/mL	NuvaRing With ATV/r Plus TDF ≥1 NRTIs
Cmax day 0	4291.0 (769.7 to 9440.0)
Cmax day 21	3583.0 (83.6 to 6578.0)

SecondaryATV PK Parameter Time to Cmax (Tmax) Determined Based on ATV Levels From Individual Participants Enrolled in Arm C

This evaluates the effect of NuvaRing on the ATV PK parameter Tmax obtained from both sampling periods, before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. Tmax defines time to maximum concentration since dose is initiated.

Time frame:: Intensive ATV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement).
Reported as:: Median · hour

ATV PK Parameter Time to Cmax (Tmax) Determined Based on ATV Levels From Individual Participants Enrolled in Arm C
hour	NuvaRing With ATV/r Plus TDF ≥1 NRTIs
Tmax day 0	2.9 (0.9 to 4.0)
Tmax day 21	3.0 (0.0 to 5.0)

SecondaryATV PK Parameter CLss/F Determined Based on ATV Levels From Individual Participants Enrolled in Arm C

This evaluates the effect of NuvaRing on the ATV PK parameter CLss/F obtained from both sampling periods, before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. CLss/f defines apparent oral clearance.

Time frame:: Intensive ATV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement).
Reported as:: Median · L/h

ATV PK Parameter CLss/F Determined Based on ATV Levels From Individual Participants Enrolled in Arm C
L/h	NuvaRing With ATV/r Plus TDF ≥1 NRTIs
CLss/F day 0	6.8 (3.3 to 34.1)
CLss/F day 21	8.2 (2.8 to 222.7)

SecondaryRitonavir (RTV) PK Parameter AUC(0-24h) Calculated Based on Intensive RTV PK Samples Obtained From Individual Participants Enrolled in Arm C

This evaluates the effect of NuvaRing on the PK parameter AUC(0-24h) of RTV before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. AUC(0-24h) defines area under the concentration-time curve over the period of 24 hours (pre-dose concentration was used to impute concentration at 24h).

Time frame:: Intensive RTV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement)
Reported as:: Median · h*ng/mL

Ritonavir (RTV) PK Parameter AUC(0-24h) Calculated Based on Intensive RTV PK Samples Obtained From Individual Participants Enrolled in Arm C
h*ng/mL	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
AUC0-24h day 0	10740.0 (3922.3 to 32632.7)
AUC0-24h day 21	7210.7 (240.0 to 31728.7)

SecondaryRTV PK Parameter Cmin Determined Based on RTV Levels From Individual Participants Enrolled in Arm C

This evaluates the effect of NuvaRing on the PK parameter Cmin of RTV before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. Cmin defines minimum concentration observed within the first 8 hours of the 24 hour dosing interval.

Time frame:: Intensive RTV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement)
Reported as:: Median · ng/mL

RTV PK Parameter Cmin Determined Based on RTV Levels From Individual Participants Enrolled in Arm C
ng/mL	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
Cmin day 0	70.0 (10.0 to 1042.0)
Cmin day 21	51.9 (10.0 to 916.9)

SecondaryRTV PK Parameter Cmax Determined Based on RTV Levels From Individual Participants Enrolled in Arm C

This evaluates the effect of NuvaRing on the PK parameter Cmax of RTV before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. Cmax defines maximum concentration observed within the first 8 hours of the 24 hour dosing interval.

Time frame:: Intensive RTV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement)
Reported as:: Median · ng/mL

RTV PK Parameter Cmax Determined Based on RTV Levels From Individual Participants Enrolled in Arm C
ng/mL	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
Cmax day 0	1437.0 (426.3 to 3078.0)
Cmax day 21	1063.0 (10.0 to 2297.0)

SecondaryRTV PK Parameter Tmax Determined Based on RTV Levels From Individual Participants Enrolled in Arm C

This evaluates the effect of NuvaRing on the PK parameter Tmax of RTV before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. Tmax defines time to maximum concentration since dose is initiated.

Time frame:: Intensive RTV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement)
Reported as:: Median · hour

RTV PK Parameter Tmax Determined Based on RTV Levels From Individual Participants Enrolled in Arm C
hour	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
Tmax day 0	3.0 (0.9 to 5.0)
Tmax day 21	3.0 (0.0 to 5.0)

SecondaryRTV PK Parameter CLss/F Determined Based on RTV Levels From Individual Participants Enrolled in Arm C

This evaluates the effect of NuvaRing on the PK parameter CLss/F of RTV before NuvaRing placement (at study day 0) and three weeks later (on study day 21), prior to NuvaRing removal. CLss/F defines apparent oral clearance.

Time frame:: Intensive RTV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement)
Reported as:: Median · hour

RTV PK Parameter CLss/F Determined Based on RTV Levels From Individual Participants Enrolled in Arm C
hour	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
CLss/F day 0	9.3 (3.1 to 25.5)
CLss/F day 21	13.9 (3.2 to 416.7)

SecondaryProportion of Participants With Plasma HIV-1 RNA Levels <40 Copies/mL

This evaluates the short-term impact of Nuvaring on virologic suppression in participants who have been administered Nuvaring alone or together with EFV or ATV/r by measuring proportion of participants with plasma HIV-1 RNA levels \<40 copies/mL at study day 0 (before vaginal ring placement) and study day 21 (three weeks after vaginal ring placement). An FDA-approved HIV-1 RNA assay was required.

Time frame:: Study day 0 and study day 21
Reported as:: Number · proportion of participants

Proportion of Participants With Plasma HIV-1 RNA Levels <40 Copies/mL
proportion of participants	NuvaRing and no ART	NuvaRing With EFV Plus ≥2 NRTIs	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
Proportion with HIV-1 RNA <40 copies/mL at day 0	0.22 (0.07 to 0.44)	0.93 (0.76 to 0.99)	0.89 (0.72 to 0.98)
Proportion with HIV-1 RNA <40 copies/mL at day 21	0.17 (0.05 to 0.37)	0.85 (0.65 to 0.96)	0.85 (0.66 to 0.96)

SecondaryPercentage of Participants With Signs and Symptoms of Grade 2 or Higher Deemed Possibly, Probably or Definitely Related to Study Treatment

This evaluates toxicity and safety of NuvaRing alone, NuvaRing with EFV, and NuvaRing with ATV/r. Signs/symptoms were graded using the DAIDS AE Grading Table was used. Participants with sign(s)/symptom(s) of grade 2 (moderate), 3 (severe), 4 (potentially life-threatening) or 5 (death) are included in the percentage. Relationship to study treatment was determined by the study co-chairs and DAIDS clinical representative.

Time frame:: From day 0 to day 28
Reported as:: Number · Percent of Participants

Percentage of Participants With Signs and Symptoms of Grade 2 or Higher Deemed Possibly, Probably or Definitely Related to Study Treatment
Percent of Participants	NuvaRing and no ART	NuvaRing With EFV Plus ≥2 NRTIs	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
Percentage of Participants With Signs and Symptoms of Grade 2 or Higher Deemed Possibly, Probably or Definitely Related to Study Treatment	7.4	3.6	3.6

SecondaryProportion of Participants With Progesterone Levels Greater Than 5 ng/mL.

This evaluates alterations in progesterone levels due to the potential PK interaction between NuvaRing and the ARVs EFV and ATV/r by examining progesterone levels at study days 0 (before vaginal ring placement), 7, 14, and 21 (before vaginal ring removal), and study day 28, without regard to menstrual cycle status at study entry.

Time frame:: Study days 0, 7, 14, 21 and 28
Reported as:: Number · proportion of participants

Proportion of Participants With Progesterone Levels Greater Than 5 ng/mL.
proportion of participants	NuvaRing and no ART	NuvaRing With EFV Plus ≥2 NRTIs	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
Proportion with progesterone >5 at day 0	0.08 (0.01 to 0.26)	0.04 (0.00 to 0.20)	0.25 (0.10 to 0.47)
Proportion with progesterone >5 at day 7	0.08 (0.01 to 0.27)	0.24 (0.09 to 0.45)	0.08 (0.01 to 0.27)
Proportion with progesterone >5 at day 14	0.00 (0.00 to 0.14)	0.04 (0.00 to 0.21)	0.00 (0.00 to 0.14)
Proportion with progesterone >5 at day 21	0.00 (0.00 to 0.14)	0.00 (0.00 to 0.14)	0.00 (0.00 to 0.14)
Proportion with progesterone >5 at day 28	0.00 (0.00 to 0.14)	0.00 (0.00 to 0.14)	0.00 (0.00 to 0.14)

Adverse events

Collected over From Day 0 to Day 28.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
NuvaRing and no ART	0/27 (0%)	0/27 (0%)	10/27 (37%)
NuvaRing With EFV Plus ≥2 NRTIs	0/28 (0%)	0/28 (0%)	20/28 (71.4%)
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs	0/28 (0%)	0/28 (0%)	18/28 (64.3%)

Most frequent other events

Showing 10 of 13

Most frequent other events
Event	NuvaRing and no ART	NuvaRing With EFV Plus ≥2 NRTIs	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
Menstruation normalInvestigations	1/27	5/28	8/28
Vaginal dischargeReproductive system and breast disorders	4/27	8/28	4/28
Vaginal haemorrhageReproductive system and breast disorders	0/27	4/28	1/28
Vulvovaginal pruritusReproductive system and breast disorders	2/27	4/28	1/28
Blood sodium decreasedInvestigations	3/27	3/28	2/28
Bacterial vaginosisInfections and infestations	1/27	3/28	1/28
Blood bilirubin increasedInvestigations	0/27	0/28	3/28
Blood glucose increasedInvestigations	2/27	0/28	1/28
Vulvovaginal candidiasisInfections and infestations	1/27	2/28	0/28
Blood bicarbonate decreasedInvestigations	0/27	2/28	0/28

Baseline characteristics

All participants enrolled.

Age, Continuous
Age, Continuous(years)	NuvaRing and no ART	NuvaRing With EFV Plus ≥2 NRTIs	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs	Total
Median	32 (22 to 48)	36 (17 to 55)	36 (22 to 50)	35 (17 to 55)

Sex: Female, Male
Sex: Female, Male(Participants)	NuvaRing and no ART	NuvaRing With EFV Plus ≥2 NRTIs	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs	Total
Female	27	28	29	84
Male	0	0	0	0

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	NuvaRing and no ART	NuvaRing With EFV Plus ≥2 NRTIs	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs	Total
White Non-Hispanic	1	1	1	3
Black Non-Hispanic	12	18	14	44
Hispanic (Regardless of Race)	11	9	9	29
Asian, Pacific Islander	3	0	5	8

Region of Enrollment
Region of Enrollment(Participants)	NuvaRing and no ART	NuvaRing With EFV Plus ≥2 NRTIs	NuvaRing With ATV/r Plus TDF and ≥1 NRTIs	Total
Puerto Rico	1	0	2	3
United States	5	14	15	34
Botswana	4	1	0	5
Brazil	3	6	5	14
South Africa	2	0	0	2
Kenya	3	3	2	8
Thailand	3	0	5	8
Peru	6	4	0	10

Study locations

21 sites

31788 Alabama CRS
Birmingham, Alabama 35294, United States
University of Southern California LA (5048)
Los Angeles, California 90033, United States
David Geffen School of Medicine at UCLA NICHD CRS (5112)
Los Angeles, California 90095-1752, United States
University of Colorado Denver NICHD CRS (5052)
Aurora, Colorado 80045, United States
University of Florida Jacksonville (5051)
Jacksonville, Florida 32209, United States
Rush University Cook County Hospital Chicago NICHD CRS (5083)
Chicago, Illinois 60612, United States
31786 New Jersey Medical School Clinical Research Center CRS
Newark, New Jersey 07103, United States
Jacobi Medical Center Bronx
Bronx, New York 10461, United States
Columbia Physicians and Surgeons CRS (30329)
New York, New York 10032, United States
The Miriam Hosp. ACTG CRS (2951)
Providence, Rhode Island 02906, United States
Gaborone Prevention/Treatment Trials CRS (12701)
Gaborone, Botswana
Instituto de Pesquisa Clinica Evandro Chagas (12101)
Rio de Janeiro, 21045, Brazil
Kenya Medical Research Institute/Center for Disease Control (KEMRI/CDC) CRS (31460)
Kisumu, 40100, Kenya
Investigaciones Medicas en Salud (INMENSA) (11302)
San Isidro, Lima, Peru
Asociacion Civil Impacta Salud y Educacion - Miraf CRS (11301)
Lima, 18 PE, Peru
Puerto Rico-AIDS CRS (5401)
San Juan, 00935, Puerto Rico
University of Puerto Rico Pediatric HIV/AIDS Research Program CRS (6601)
San Juan, 00935, Puerto Rico
San Juan Hospital PR NICHD CRS (5031)
San Juan, 00936, Puerto Rico
Shandukani Research CRS (8051)
Johannesburg, Gauteng 2038, South Africa
31802 Thai Red Cross AIDS Research Center Treatment (TRC-ARC Treatment) CRS
Bangkok, Patumwan 10330, Thailand
31784 Chiang Mai University HIV Treatment CRS
Chiang Mai, 50200, Thailand

References and documents

Publications

Scarsi KK, Cramer YS, Rosenkranz SL, Aweeka F, Berzins B, Coombs RW, Coughlin K, Moran LE, Zorrilla CD, Akelo V, Aziz M, Friedman RK, Gingrich D, Swaminathan S, Godfrey C, Cohn SE; AIDS Clinical Trials Group A5316 Study Team. Antiretroviral therapy and vaginally administered contraceptive hormones: a three-arm, pharmacokinetic study. Lancet HIV. 2019 Sep;6(9):e601-e612. doi: 10.1016/S2352-3018(19)30155-9. PubMed 31498109 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 6, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01903031
Lead sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Responsible party: Sponsor
First posted: Jul 19, 2013
Start date: Dec 30, 2014
Primary completion: Oct 3, 2016
Completion: Oct 10, 2016
Results posted: Jan 4, 2018
Last update: Jun 6, 2018

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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