Trial Outcomes & Findings for Evaluating Pharmacokinetic Interactions With Vaginal Ring Contraceptives and ART (NCT NCT01903031)
NCT ID: NCT01903031
Last Updated: 2018-06-06
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
84 participants
Primary outcome timeframe
Day 21
Results posted on
2018-06-06
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 milestones
| Measure |
NuvaRing and no ART
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
Overall Study
STARTED
|
27
|
28
|
29
|
|
Overall Study
COMPLETED
|
25
|
25
|
24
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
5
|
Reasons for withdrawal
| Measure |
NuvaRing and no ART
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
Overall Study
Not Able to Attend Clinic
|
1
|
1
|
0
|
|
Overall Study
Missed Day 21 Primary Endpoint Visit
|
1
|
0
|
0
|
|
Overall Study
Adverse Event
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
1
|
|
Overall Study
Protocol Violation
|
0
|
0
|
2
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
1
|
|
Overall Study
NuvaRing removed prior to Day 21 visit
|
0
|
0
|
1
|
Baseline Characteristics
Evaluating Pharmacokinetic Interactions With Vaginal Ring Contraceptives and ART
Baseline characteristics by cohort
| Measure |
NuvaRing and no ART
n=27 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
n=28 Participants
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
n=29 Participants
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
Total
n=84 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
32 years
n=5 Participants
|
36 years
n=7 Participants
|
36 years
n=5 Participants
|
35 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
84 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White Non-Hispanic
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black Non-Hispanic
|
12 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
44 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Hispanic (Regardless of Race)
|
11 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
29 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian, Pacific Islander
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Region of Enrollment
Puerto Rico
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
5 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
34 Participants
n=4 Participants
|
|
Region of Enrollment
Botswana
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Region of Enrollment
Brazil
|
3 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Region of Enrollment
South Africa
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Region of Enrollment
Kenya
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Region of Enrollment
Thailand
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Region of Enrollment
Peru
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Day 21Population: Participants who provided the Etonogestrel PK sample at day 21 were included in the analysis.
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).
Outcome measures
| Measure |
NuvaRing and no ART
n=25 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
n=25 Participants
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
n=24 Participants
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
Etonogestrel Concentrations at Study Day 21
|
1860.00 pg/mL
Interval 665.0 to 3590.0
|
429.00 pg/mL
Interval 125.0 to 1180.0
|
3290.00 pg/mL
Interval 730.0 to 6920.0
|
PRIMARY outcome
Timeframe: Day 21Population: Participants who provided the Ethinyl Estradiol PK sample at day 21 were included in the analysis.
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).
Outcome measures
| Measure |
NuvaRing and no ART
n=25 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
n=25 Participants
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
n=24 Participants
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
Ethinyl Estradiol Concentrations at Study Day 21
|
21.30 pg/mL
Interval 6.46 to 51.0
|
11.40 pg/mL
Interval 2.5 to 21.0
|
16.05 pg/mL
Interval 2.5 to 26.4
|
SECONDARY outcome
Timeframe: Study days 7 and 14Population: Participants who provided the Etonogestrel PK samples at day 7 and at day 14 were included in the analysis.
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).
Outcome measures
| Measure |
NuvaRing and no ART
n=25 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
n=25 Participants
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
n=24 Participants
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
Etonogestrel Concentrations Obtained on Study Days 7 and 14
Concentration at Day 7
|
1970.00 pg/mL
Interval 703.0 to 3220.0
|
427.00 pg/mL
Interval 125.0 to 916.0
|
3250.00 pg/mL
Interval 1330.0 to 4960.0
|
|
Etonogestrel Concentrations Obtained on Study Days 7 and 14
Concentration at Day 14
|
2070.00 pg/mL
Interval 648.0 to 3720.0
|
437.00 pg/mL
Interval 125.0 to 1090.0
|
3530.00 pg/mL
Interval 725.0 to 6100.0
|
SECONDARY outcome
Timeframe: Study days 7 and 14Population: Participants who provided the Ethinyl estradiol PK samples at day 7 and at day 14 were included in the analysis.
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).
Outcome measures
| Measure |
NuvaRing and no ART
n=25 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
n=25 Participants
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
n=24 Participants
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
Ethinyl Estradiol Concentrations Obtained on Study Days 7 and 14.
Concentration at Day 7
|
18.05 pg/mL
Interval 6.71 to 50.9
|
9.98 pg/mL
Interval 2.5 to 18.7
|
15.70 pg/mL
Interval 5.48 to 24.3
|
|
Ethinyl Estradiol Concentrations Obtained on Study Days 7 and 14.
Concentration at Day 14
|
19.70 pg/mL
Interval 6.51 to 47.9
|
10.50 pg/mL
Interval 2.5 to 18.6
|
16.55 pg/mL
Interval 6.76 to 26.9
|
SECONDARY outcome
Timeframe: 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).Population: The analysis population is the 24 A5316 participants enrolled in Arm B (NuvaRing with EFV arm plus 2 or more NRTIs) eligible for the secondary outcome of EFV PK parameters.
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).
Outcome measures
| Measure |
NuvaRing and no ART
n=24 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
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
AUC0-24h day 0
|
68949.1 h*ng/mL
Interval 27114.3 to 367995.4
|
—
|
—
|
|
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
AUC0-24h day 21
|
57795.9 h*ng/mL
Interval 26326.3 to 362821.3
|
—
|
—
|
SECONDARY outcome
Timeframe: 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).Population: The analysis population is the 24 A5316 participants enrolled in Arm B (NuvaRing with EFV arm plus 2 or more NRTIs) eligible for the secondary outcome of EFV PK parameters.
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.
Outcome measures
| Measure |
NuvaRing and no ART
n=24 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
EFV PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B
Cmin day 0
|
2121.5 ng/mL
Interval 903.7 to 13620.0
|
—
|
—
|
|
EFV PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B
Cmin day 21
|
1766.0 ng/mL
Interval 10.0 to 12930.0
|
—
|
—
|
SECONDARY outcome
Timeframe: 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).Population: The analysis population is the 24 A5316 participants enrolled in Arm B (NuvaRing with EFV arm plus 2 or more NRTIs) eligible for the secondary outcome of EFV PK parameters.
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.
Outcome measures
| Measure |
NuvaRing and no ART
n=24 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
EFV PK Parameter Maximum Plasma Concentration (Cmax) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B
Cmax day 0
|
4541.0 ng/mL
Interval 1347.0 to 18670.0
|
—
|
—
|
|
EFV PK Parameter Maximum Plasma Concentration (Cmax) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B
Cmax day 21
|
3786.0 ng/mL
Interval 2231.0 to 19110.0
|
—
|
—
|
SECONDARY outcome
Timeframe: 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).Population: The analysis population is the 24 A5316 participants enrolled in Arm B (NuvaRing with EFV arm plus 2 or more NRTIs) eligible for the secondary outcome of EFV PK parameters.
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
Outcome measures
| Measure |
NuvaRing and no ART
n=24 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
EFV PK Parameter Clearance (CLss/F) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B
CLss/F day 0
|
8.7 L/h
Interval 1.6 to 22.1
|
—
|
—
|
|
EFV PK Parameter Clearance (CLss/F) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B
CLss/F day 21
|
10.4 L/h
Interval 1.7 to 22.8
|
—
|
—
|
SECONDARY outcome
Timeframe: 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)Population: The analysis population is the 23 A5316 participants enrolled in Arm C (NuvaRing with ATV/r arm plus TDF and one or more NRTIs) eligible for the secondary outcome of ATV PK parameters.
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).
Outcome measures
| Measure |
NuvaRing and no ART
n=23 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
ATV PK Parameter AUC(0-24h) Calculated Based on Intensive Atazanavir (ATV) PK Samples Obtained From Individual Participants Enrolled in Arm C
AUC0-24h day 0
|
44313.7 h*ng/mL
Interval 8802.3 to 91766.5
|
—
|
—
|
|
ATV PK Parameter AUC(0-24h) Calculated Based on Intensive Atazanavir (ATV) PK Samples Obtained From Individual Participants Enrolled in Arm C
AUC0-24h day 21
|
36764.7 h*ng/mL
Interval 1346.9 to 108450.6
|
—
|
—
|
SECONDARY outcome
Timeframe: 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).Population: The analysis population is the 23 A5316 participants enrolled in Arm C (NuvaRing with ATV/r arm plus TDF and one or more NRTIs) eligible for the secondary outcome of ATV PK parameters.
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.
Outcome measures
| Measure |
NuvaRing and no ART
n=23 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
ATV PK Parameter Cmin Determined Based on ATV Levels From Individual Participants Enrolled in Arm C
Cmin day 0
|
796.7 ng/mL
Interval 10.0 to 2731.0
|
—
|
—
|
|
ATV PK Parameter Cmin Determined Based on ATV Levels From Individual Participants Enrolled in Arm C
Cmin day 21
|
599.4 ng/mL
Interval 10.0 to 3599.0
|
—
|
—
|
SECONDARY outcome
Timeframe: 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).Population: The analysis population is the 23 A5316 participants enrolled in Arm C (NuvaRing with ATV/r arm plus TDF and one or more NRTIs) eligible for the secondary outcome of ATV PK parameters.
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.
Outcome measures
| Measure |
NuvaRing and no ART
n=23 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
ATV PK Parameter Cmax Determined Based on ATV Levels From Individual Participants Enrolled in Arm C
Cmax day 0
|
4291.0 ng/mL
Interval 769.7 to 9440.0
|
—
|
—
|
|
ATV PK Parameter Cmax Determined Based on ATV Levels From Individual Participants Enrolled in Arm C
Cmax day 21
|
3583.0 ng/mL
Interval 83.6 to 6578.0
|
—
|
—
|
SECONDARY outcome
Timeframe: 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).Population: The analysis population is the 23 A5316 participants enrolled in Arm C (NuvaRing with ATV/r arm plus TDF and one or more NRTIs) eligible for the secondary outcome of ATV PK parameters.
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.
Outcome measures
| Measure |
NuvaRing and no ART
n=23 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
ATV PK Parameter Time to Cmax (Tmax) Determined Based on ATV Levels From Individual Participants Enrolled in Arm C
Tmax day 0
|
2.9 hour
Interval 0.9 to 4.0
|
—
|
—
|
|
ATV PK Parameter Time to Cmax (Tmax) Determined Based on ATV Levels From Individual Participants Enrolled in Arm C
Tmax day 21
|
3.0 hour
Interval 0.0 to 5.0
|
—
|
—
|
SECONDARY outcome
Timeframe: 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).Population: The analysis population is the 23 A5316 participants enrolled in Arm C (NuvaRing with ATV/r arm plus TDF and one or more NRTIs) eligible for the secondary outcome of ATV PK parameters.
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.
Outcome measures
| Measure |
NuvaRing and no ART
n=23 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
ATV PK Parameter CLss/F Determined Based on ATV Levels From Individual Participants Enrolled in Arm C
CLss/F day 0
|
6.8 L/h
Interval 3.3 to 34.1
|
—
|
—
|
|
ATV PK Parameter CLss/F Determined Based on ATV Levels From Individual Participants Enrolled in Arm C
CLss/F day 21
|
8.2 L/h
Interval 2.8 to 222.7
|
—
|
—
|
SECONDARY outcome
Timeframe: 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)Population: The analysis population is the 23 A5316 participants enrolled in Arm C (NuvaRing with ATV/r arm plus TDF and one or more NRTIs) eligible for the secondary outcome of RTV PK parameters.
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).
Outcome measures
| Measure |
NuvaRing and no ART
n=23 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
Ritonavir (RTV) PK Parameter AUC(0-24h) Calculated Based on Intensive RTV PK Samples Obtained From Individual Participants Enrolled in Arm C
AUC0-24h day 0
|
10740.0 h*ng/mL
Interval 3922.3 to 32632.7
|
—
|
—
|
|
Ritonavir (RTV) PK Parameter AUC(0-24h) Calculated Based on Intensive RTV PK Samples Obtained From Individual Participants Enrolled in Arm C
AUC0-24h day 21
|
7210.7 h*ng/mL
Interval 240.0 to 31728.7
|
—
|
—
|
SECONDARY outcome
Timeframe: 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)Population: The analysis population is the 23 A5316 participants enrolled in Arm C (NuvaRing with ATV/r arm plus TDF and one or more NRTIs) eligible for the secondary outcome of RTV PK parameters.
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.
Outcome measures
| Measure |
NuvaRing and no ART
n=23 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
RTV PK Parameter Cmin Determined Based on RTV Levels From Individual Participants Enrolled in Arm C
Cmin day 0
|
70.0 ng/mL
Interval 10.0 to 1042.0
|
—
|
—
|
|
RTV PK Parameter Cmin Determined Based on RTV Levels From Individual Participants Enrolled in Arm C
Cmin day 21
|
51.9 ng/mL
Interval 10.0 to 916.9
|
—
|
—
|
SECONDARY outcome
Timeframe: 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)Population: The analysis population is the 23 A5316 participants enrolled in Arm C (NuvaRing with ATV/r arm plus TDF and one or more NRTIs) eligible for the secondary outcome of RTV PK parameters.
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.
Outcome measures
| Measure |
NuvaRing and no ART
n=23 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
RTV PK Parameter Cmax Determined Based on RTV Levels From Individual Participants Enrolled in Arm C
Cmax day 0
|
1437.0 ng/mL
Interval 426.3 to 3078.0
|
—
|
—
|
|
RTV PK Parameter Cmax Determined Based on RTV Levels From Individual Participants Enrolled in Arm C
Cmax day 21
|
1063.0 ng/mL
Interval 10.0 to 2297.0
|
—
|
—
|
SECONDARY outcome
Timeframe: 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)Population: The analysis population is the 23 A5316 participants enrolled in Arm C (NuvaRing with ATV/r arm plus TDF and one or more NRTIs) eligible for the secondary outcome of RTV PK parameters.
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.
Outcome measures
| Measure |
NuvaRing and no ART
n=23 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
RTV PK Parameter Tmax Determined Based on RTV Levels From Individual Participants Enrolled in Arm C
Tmax day 0
|
3.0 hour
Interval 0.9 to 5.0
|
—
|
—
|
|
RTV PK Parameter Tmax Determined Based on RTV Levels From Individual Participants Enrolled in Arm C
Tmax day 21
|
3.0 hour
Interval 0.0 to 5.0
|
—
|
—
|
SECONDARY outcome
Timeframe: 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)Population: The analysis population is the 23 A5316 participants enrolled in Arm C (NuvaRing with ATV/r arm plus TDF and one or more NRTIs) eligible for the secondary outcome of RTV PK parameters.
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.
Outcome measures
| Measure |
NuvaRing and no ART
n=23 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
RTV PK Parameter CLss/F Determined Based on RTV Levels From Individual Participants Enrolled in Arm C
CLss/F day 0
|
9.3 hour
Interval 3.1 to 25.5
|
—
|
—
|
|
RTV PK Parameter CLss/F Determined Based on RTV Levels From Individual Participants Enrolled in Arm C
CLss/F day 21
|
13.9 hour
Interval 3.2 to 416.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Study day 0 and study day 21Population: All participants in whom NuvaRing was inserted and with HIV-1 RNA data available.
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.
Outcome measures
| Measure |
NuvaRing and no ART
n=27 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
n=28 Participants
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
n=28 Participants
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
Proportion of Participants With Plasma HIV-1 RNA Levels <40 Copies/mL
Proportion with HIV-1 RNA <40 copies/mL at day 0
|
0.22 proportion of participants
Interval 0.07 to 0.44
|
0.93 proportion of participants
Interval 0.76 to 0.99
|
0.89 proportion of participants
Interval 0.72 to 0.98
|
|
Proportion of Participants With Plasma HIV-1 RNA Levels <40 Copies/mL
Proportion with HIV-1 RNA <40 copies/mL at day 21
|
0.17 proportion of participants
Interval 0.05 to 0.37
|
0.85 proportion of participants
Interval 0.65 to 0.96
|
0.85 proportion of participants
Interval 0.66 to 0.96
|
SECONDARY outcome
Timeframe: From day 0 to day 28Population: All participants in whom NuvaRing was inserted
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.
Outcome measures
| Measure |
NuvaRing and no ART
n=27 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
n=28 Participants
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
n=28 Participants
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
Percentage of Participants With Signs and Symptoms of Grade 2 or Higher Deemed Possibly, Probably or Definitely Related to Study Treatment
|
7.4 Percent of Participants
|
3.6 Percent of Participants
|
3.6 Percent of Participants
|
SECONDARY outcome
Timeframe: Study days 0, 7, 14, 21 and 28Population: All participants included in the primary analyses who had progesterone data available. One participant on the EFV arm is excluded at day 14 visit because NuvaRing was out of the body for \>3 hours leading up to the visit.
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.
Outcome measures
| Measure |
NuvaRing and no ART
n=25 Participants
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
n=25 Participants
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
n=24 Participants
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
Proportion of Participants With Progesterone Levels Greater Than 5 ng/mL.
Proportion with progesterone >5 at day 0
|
0.08 proportion of participants
Interval 0.01 to 0.26
|
0.04 proportion of participants
Interval 0.0 to 0.2
|
0.25 proportion of participants
Interval 0.1 to 0.47
|
|
Proportion of Participants With Progesterone Levels Greater Than 5 ng/mL.
Proportion with progesterone >5 at day 7
|
0.08 proportion of participants
Interval 0.01 to 0.27
|
0.24 proportion of participants
Interval 0.09 to 0.45
|
0.08 proportion of participants
Interval 0.01 to 0.27
|
|
Proportion of Participants With Progesterone Levels Greater Than 5 ng/mL.
Proportion with progesterone >5 at day 14
|
0.00 proportion of participants
Interval 0.0 to 0.14
|
0.04 proportion of participants
Interval 0.0 to 0.21
|
0.00 proportion of participants
Interval 0.0 to 0.14
|
|
Proportion of Participants With Progesterone Levels Greater Than 5 ng/mL.
Proportion with progesterone >5 at day 21
|
0.00 proportion of participants
Interval 0.0 to 0.14
|
0.00 proportion of participants
Interval 0.0 to 0.14
|
0.00 proportion of participants
Interval 0.0 to 0.14
|
|
Proportion of Participants With Progesterone Levels Greater Than 5 ng/mL.
Proportion with progesterone >5 at day 28
|
0.00 proportion of participants
Interval 0.0 to 0.14
|
0.00 proportion of participants
Interval 0.0 to 0.14
|
0.00 proportion of participants
Interval 0.0 to 0.14
|
Adverse Events
NuvaRing and no ART
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
NuvaRing With EFV Plus ≥2 NRTIs
Serious events: 0 serious events
Other events: 20 other events
Deaths: 0 deaths
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
Serious events: 0 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
NuvaRing and no ART
n=27 participants at risk
Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
|
NuvaRing With EFV Plus ≥2 NRTIs
n=28 participants at risk
NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
|
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
n=28 participants at risk
NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
|
|---|---|---|---|
|
Infections and infestations
Vulvovaginal candidiasis
|
3.7%
1/27 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
7.1%
2/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
0.00%
0/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
|
Investigations
Blood bicarbonate decreased
|
0.00%
0/27 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
7.1%
2/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
0.00%
0/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/27 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
0.00%
0/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
10.7%
3/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
|
Investigations
Blood glucose increased
|
7.4%
2/27 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
0.00%
0/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
3.6%
1/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
|
Investigations
Blood sodium decreased
|
11.1%
3/27 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
10.7%
3/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
7.1%
2/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
|
Investigations
Menstruation normal
|
3.7%
1/27 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
17.9%
5/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
28.6%
8/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
|
Psychiatric disorders
Libido decreased
|
0.00%
0/27 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
0.00%
0/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
7.1%
2/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
3.7%
1/27 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
3.6%
1/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
7.1%
2/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
|
Reproductive system and breast disorders
Metrorrhagia
|
3.7%
1/27 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
7.1%
2/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
3.6%
1/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
|
Reproductive system and breast disorders
Vaginal discharge
|
14.8%
4/27 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
28.6%
8/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
14.3%
4/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.00%
0/27 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
14.3%
4/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
3.6%
1/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
|
Reproductive system and breast disorders
Vulvovaginal pruritus
|
7.4%
2/27 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
14.3%
4/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
3.6%
1/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
|
Infections and infestations
Bacterial vaginosis
|
3.7%
1/27 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
10.7%
3/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
3.6%
1/28 • From Day 0 to Day 28.
Protocol required reporting: diagnoses (identified by ACTG criteria for clinical events and other diseases); signs/symptoms of grade ≥3; selected signs/symptoms of grade ≤2 (gynecological and/or deemed related to the NuvaRing or study procedures); hematology, LFTs and chemistry findings of grade ≥2. The DAIDS AE Grading Table and Version 2.0 of the DAIDS EAE Manual were used. One participant on ATV/r arm was excluded from AE analyses because insertion of NuvaRing could not be confirmed.
|
Additional Information
ACTG Clinicaltrials.gov Coordinator
ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Phone: (301) 628-3313
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER