Trial Outcomes & Findings for NNRTI vs PI Regimens for HIV Infected Women After They Have Taken Nevirapine to Prevent Mother-To-Child HIV Transmission (NCT NCT00089505)

Last Updated: 2018-10-12

Results Overview

5th and 10th Percentiles in weeks from randomization to virologic failure (VF) or death. VF is defined as a plasma HIV-1 RNA level that is 1 log10 below baseline 12 weeks after treatment is initiated or as a plasma HIV-1 RNA level that is \>=400 copies/mL at or after 24 weeks of treatment, regardless of whether randomized treatment was being taken at the time of VF.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

745 participants

Primary outcome timeframe

Through database cutoff for DSMB review (by October 6, 2008) with median follow-up 72 weeks and range from 0 to 144 weeks.

Results posted on

2018-10-12

Participant Flow

Study participants were recruited at 10 sites from 7 African countries: 3 from South Africa, 2 from Kenya, and 1 each in Botswana, Malawi, Uganda, Zambia and Zimbabwe, between November 2006 to July 2008. The Botswana site enrolled participants from two locations.

HIV-infected, treatment-naive women, at least 13 years of age with CD4+ count\<200 cells/mm\^3. Four participants were randomized but did not start treatment.

Participant milestones

Participant milestones
Measure	NVP/NVP For participants had single dose Nevirapine (SD NVP) exposure prior to study entry, Emtricitabine capsules(FTC) 200mg (1 capsule orally), Tenofovir disproxil fumerate (TDF) 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily in the morning for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive Lopinovir/Ritonovir (LPV/RTV)400/100mg (3 capsules orally) twice daily plus two more Nucleoside reverse transcriptase inhibitors (NRTIs). Following the review on 6 October 2008, the Data Safety Monitoring Board(DSMB) recommended release of the results from this arm.	NVP/LPV_r For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP 200mg (1 tablet orally) daily for 14 days before taking it twice daily. plus 2 more NRTIs. Following the review on 6 October 2008, the DSMB recommended release of the results from this arm.	NoNVP/NVP For participants had NO SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally), TDF 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive LPV/RTV 400/100mg (3 capsules orally) twice daily plus two more NRTIs.	NoNVP/LPV_r For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) once daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP daily 200mg (1 tablet orally) for 14 days before taking it twice daily plus 2 more NRTIs.
Overall Study STARTED	121	120	249	251
Overall Study COMPLETED	112	118	228	230
Overall Study NOT COMPLETED	9	2	21	21

Reasons for withdrawal

Reasons for withdrawal
Measure	NVP/NVP For participants had single dose Nevirapine (SD NVP) exposure prior to study entry, Emtricitabine capsules(FTC) 200mg (1 capsule orally), Tenofovir disproxil fumerate (TDF) 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily in the morning for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive Lopinovir/Ritonovir (LPV/RTV)400/100mg (3 capsules orally) twice daily plus two more Nucleoside reverse transcriptase inhibitors (NRTIs). Following the review on 6 October 2008, the Data Safety Monitoring Board(DSMB) recommended release of the results from this arm.	NVP/LPV_r For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP 200mg (1 tablet orally) daily for 14 days before taking it twice daily. plus 2 more NRTIs. Following the review on 6 October 2008, the DSMB recommended release of the results from this arm.	NoNVP/NVP For participants had NO SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally), TDF 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive LPV/RTV 400/100mg (3 capsules orally) twice daily plus two more NRTIs.	NoNVP/LPV_r For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) once daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP daily 200mg (1 tablet orally) for 14 days before taking it twice daily plus 2 more NRTIs.
Overall Study Death	4	1	5	8
Overall Study Withdrawal by Subject	3	0	6	6
Overall Study Lost to Follow-up	1	1	9	7
Overall Study Physician Decision	1	0	0	0
Overall Study Protocol Violation	0	0	1	0

Baseline Characteristics

NNRTI vs PI Regimens for HIV Infected Women After They Have Taken Nevirapine to Prevent Mother-To-Child HIV Transmission

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NVP/NVP n=121 Participants For participants had single dose Nevirapine (SD NVP) exposure prior to study entry, Emtricitabine capsules(FTC) 200mg (1 capsule orally), Tenofovir disproxil fumerate (TDF) 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily in the morning for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive Lopinovir/Ritonovir (LPV/RTV)400/100mg (3 capsules orally) twice daily plus two more Nucleoside reverse transcriptase inhibitors (NRTIs). Following the review on 6 October 2008, the Data Safety Monitoring Board(DSMB) recommended release of the results from this arm.	NVP/LPV_r n=120 Participants For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP 200mg (1 tablet orally) daily for 14 days before taking it twice daily. plus 2 more NRTIs. Following the review on 6 October 2008, the DSMB recommended release of the results from this arm.	NoNVP/NVP n=249 Participants For participants had NO SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally), TDF 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive LPV/RTV 400/100mg (3 capsules orally) twice daily plus two more NRTIs.	NoNVP/LPV_r n=251 Participants For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) once daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP daily 200mg (1 tablet orally) for 14 days before taking it twice daily plus 2 more NRTIs.	Total n=741 Participants Total of all reporting groups
Age, Continuous	30 years STANDARD_DEVIATION 5 • n=5 Participants	31 years STANDARD_DEVIATION 5 • n=7 Participants	35 years STANDARD_DEVIATION 7 • n=5 Participants	35 years STANDARD_DEVIATION 8 • n=4 Participants	33 years STANDARD_DEVIATION 7 • n=21 Participants
Age, Customized Between 13 and 19 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants	2 participants n=21 Participants
Age, Customized Between 20 and 29 years	56 participants n=5 Participants	49 participants n=7 Participants	63 participants n=5 Participants	64 participants n=4 Participants	232 participants n=21 Participants
Age, Customized Between 30 and 39 years	59 participants n=5 Participants	62 participants n=7 Participants	125 participants n=5 Participants	124 participants n=4 Participants	370 participants n=21 Participants
Age, Customized Between 40 and 49 years	5 participants n=5 Participants	9 participants n=7 Participants	54 participants n=5 Participants	49 participants n=4 Participants	117 participants n=21 Participants
Age, Customized >=50 years	1 participants n=5 Participants	0 participants n=7 Participants	7 participants n=5 Participants	12 participants n=4 Participants	20 participants n=21 Participants
Sex: Female, Male Female	121 Participants n=5 Participants	120 Participants n=7 Participants	249 Participants n=5 Participants	251 Participants n=4 Participants	741 Participants n=21 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	0 Participants n=21 Participants
Region of Enrollment Kenya	21 participants n=5 Participants	23 participants n=7 Participants	45 participants n=5 Participants	48 participants n=4 Participants	137 participants n=21 Participants
Region of Enrollment Zambia	12 participants n=5 Participants	12 participants n=7 Participants	19 participants n=5 Participants	21 participants n=4 Participants	64 participants n=21 Participants
Region of Enrollment Botswana	13 participants n=5 Participants	12 participants n=7 Participants	33 participants n=5 Participants	30 participants n=4 Participants	88 participants n=21 Participants
Region of Enrollment Uganda	8 participants n=5 Participants	9 participants n=7 Participants	22 participants n=5 Participants	21 participants n=4 Participants	60 participants n=21 Participants
Region of Enrollment Malawi	14 participants n=5 Participants	10 participants n=7 Participants	22 participants n=5 Participants	22 participants n=4 Participants	68 participants n=21 Participants
Region of Enrollment South Africa	35 participants n=5 Participants	36 participants n=7 Participants	69 participants n=5 Participants	67 participants n=4 Participants	207 participants n=21 Participants
Region of Enrollment Zimbabwe	18 participants n=5 Participants	18 participants n=7 Participants	39 participants n=5 Participants	42 participants n=4 Participants	117 participants n=21 Participants
CD4 count Categorical <50 cells/mm^3	14 participants n=5 Participants	11 participants n=7 Participants	32 participants n=5 Participants	36 participants n=4 Participants	93 participants n=21 Participants
CD4 count Categorical Between 50 to 99 cells/mm^3	18 participants n=5 Participants	23 participants n=7 Participants	63 participants n=5 Participants	53 participants n=4 Participants	157 participants n=21 Participants
CD4 count Categorical Between 100 to 149 cells/mm^3	35 participants n=5 Participants	38 participants n=7 Participants	65 participants n=5 Participants	78 participants n=4 Participants	216 participants n=21 Participants
CD4 count Categorical Between 150 to 199 cells/mm^3	37 participants n=5 Participants	32 participants n=7 Participants	58 participants n=5 Participants	57 participants n=4 Participants	184 participants n=21 Participants
CD4 count Categorical Between 200 to 249 cells/mm^3	15 participants n=5 Participants	12 participants n=7 Participants	18 participants n=5 Participants	19 participants n=4 Participants	64 participants n=21 Participants
CD4 count Categorical Between 250 to 299 cells/mm^3	1 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants	4 participants n=4 Participants	18 participants n=21 Participants
CD4 count Categorical Between 300 to 349 cells/mm^3	1 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	5 participants n=21 Participants
CD4 count Categorical >=350 cells/mm^3	0 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	4 participants n=21 Participants
CD4 count Continuous	136 cell/mm^3 STANDARD_DEVIATION 60 • n=5 Participants	135 cell/mm^3 STANDARD_DEVIATION 61 • n=7 Participants	126 cell/mm^3 STANDARD_DEVIATION 68 • n=5 Participants	125 cell/mm^3 STANDARD_DEVIATION 71 • n=4 Participants	129 cell/mm^3 STANDARD_DEVIATION 67 • n=21 Participants
Baseline HIV-1 RNA Categorial Between 400 and 999 copies/mL	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants	4 participants n=21 Participants
Baseline HIV-1 RNA Categorial Between 1000 and 9,999 copies/mL	5 participants n=5 Participants	8 participants n=7 Participants	18 participants n=5 Participants	11 participants n=4 Participants	42 participants n=21 Participants
Baseline HIV-1 RNA Categorial Between 10,000 and 99,999 copies/mL	44 participants n=5 Participants	33 participants n=7 Participants	81 participants n=5 Participants	88 participants n=4 Participants	246 participants n=21 Participants
Baseline HIV-1 RNA Categorial Between 100,000 and 749,999 copies/mL	61 participants n=5 Participants	63 participants n=7 Participants	123 participants n=5 Participants	128 participants n=4 Participants	375 participants n=21 Participants
Baseline HIV-1 RNA Categorial >=750,000 copies/mL	11 participants n=5 Participants	15 participants n=7 Participants	26 participants n=5 Participants	22 participants n=4 Participants	74 participants n=21 Participants
HIV-1 RNA Continuous	5.2 log 10 copies/mL n=5 Participants	5.1 log 10 copies/mL n=7 Participants	5.2 log 10 copies/mL n=5 Participants	5.2 log 10 copies/mL n=4 Participants	5.2 log 10 copies/mL n=21 Participants
WHO stage Clinical stage I	44 participants n=5 Participants	56 participants n=7 Participants	97 participants n=5 Participants	93 participants n=4 Participants	290 participants n=21 Participants
WHO stage Clinical stage II	42 participants n=5 Participants	38 participants n=7 Participants	72 participants n=5 Participants	67 participants n=4 Participants	219 participants n=21 Participants
WHO stage Clinical stage III	30 participants n=5 Participants	25 participants n=7 Participants	73 participants n=5 Participants	80 participants n=4 Participants	208 participants n=21 Participants
WHO stage Clinical stage IV	5 participants n=5 Participants	1 participants n=7 Participants	7 participants n=5 Participants	11 participants n=4 Participants	24 participants n=21 Participants

PRIMARY outcome

Timeframe: Through database cutoff for DSMB review (by October 6, 2008) with median follow-up 72 weeks and range from 0 to 144 weeks.

Population: Numbers presented use the intent-to-treat approach (i.e. ignoring changes from randomized treatment).

Outcome measures

Outcome measures
Measure	NVP/NVP n=121 Participants For participants had single dose Nevirapine (SD NVP) exposure prior to study entry, Emtricitabine capsules(FTC) 200mg (1 capsule orally), Tenofovir disproxil fumerate (TDF) 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily in the morning for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive Lopinovir/Ritonovir (LPV/RTV)400/100mg (3 capsules orally) twice daily plus two more Nucleoside reverse transcriptase inhibitors (NRTIs). Following the review on 6 October 2008, the Data Safety Monitoring Board(DSMB) recommended release of the results from this arm.	NVP/LPV_r n=120 Participants For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP 200mg (1 tablet orally) daily for 14 days before taking it twice daily. plus 2 more NRTIs. Following the review on 6 October 2008, the DSMB recommended release of the results from this arm.	NoNVP/NVP For participants had NO SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally), TDF 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive LPV/RTV 400/100mg (3 capsules orally) twice daily plus two more NRTIs.	NoNVP/LPV_r For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) once daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP daily 200mg (1 tablet orally) for 14 days before taking it twice daily plus 2 more NRTIs.
Time From Randomization to Virologic Failure or Death for Participants Who Had SD NVP Exposure Prior to Study Entry 5th percentile	12 weeks Interval 6.0 to 12.0	60 weeks Interval 12.0 to 84.0	—	—
Time From Randomization to Virologic Failure or Death for Participants Who Had SD NVP Exposure Prior to Study Entry 10th percentile	12 weeks Interval 12.0 to 24.0	84 weeks Interval 60.0 to Not estimable as the upper limit for survival function at all weeks is above 90%	—	—
Time From Randomization to Virologic Failure or Death for Participants Who Had SD NVP Exposure Prior to Study Entry 25th percentile	60 weeks Interval 24.0 to Not estimable as the upper limit for survival function at all weeks is above 75%	NA weeks Not estimable as the estimates for survival function at all weeks is above 75%	—	—

PRIMARY outcome

Timeframe: Throughout study with median follow-up 72 weeks and range from 0 to 180 weeks.

Population: The analysis was intent to treat per protocol.

Outcome measures

Outcome measures
Measure	NVP/NVP For participants had single dose Nevirapine (SD NVP) exposure prior to study entry, Emtricitabine capsules(FTC) 200mg (1 capsule orally), Tenofovir disproxil fumerate (TDF) 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily in the morning for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive Lopinovir/Ritonovir (LPV/RTV)400/100mg (3 capsules orally) twice daily plus two more Nucleoside reverse transcriptase inhibitors (NRTIs). Following the review on 6 October 2008, the Data Safety Monitoring Board(DSMB) recommended release of the results from this arm.	NVP/LPV_r For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP 200mg (1 tablet orally) daily for 14 days before taking it twice daily. plus 2 more NRTIs. Following the review on 6 October 2008, the DSMB recommended release of the results from this arm.	NoNVP/NVP n=249 Participants For participants had NO SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally), TDF 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive LPV/RTV 400/100mg (3 capsules orally) twice daily plus two more NRTIs.	NoNVP/LPV_r n=251 Participants For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) once daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP daily 200mg (1 tablet orally) for 14 days before taking it twice daily plus 2 more NRTIs.
Time From Randomization to Virologic Failure or Death for Participants Without SD NVP Exposure Prior to Study Entry 5th percentile	—	—	24 weeks Interval 12.0 to 24.0	12 weeks Interval 12.0 to 24.0
Time From Randomization to Virologic Failure or Death for Participants Without SD NVP Exposure Prior to Study Entry 10th percentile	—	—	36 weeks Interval 24.0 to 48.0	36 weeks Interval 12.0 to 60.0
Time From Randomization to Virologic Failure or Death for Participants Without SD NVP Exposure Prior to Study Entry 25th percentile	—	—	NA weeks Interval 120.0 to Not estimable as the estimate for survival function at all weeks is above 75%	132 weeks Interval 96.0 to Not estimable as the upper limit for survival function at all weeks is above 75%

SECONDARY outcome

Timeframe: Through database cutoff for DSMB review (by October 6, 2008) for NVP/NVP and NVP/LPV_r. Throughout study for NoNVP/NVP and NoNVP/LPV_r.

Population: Numbers presented use the intent-to-treat approach (i.e. ignoring changes from randomized treatment).

Virologic failure (VF) is defined as a plasma HIV-1 RNA level that is 1 log10 below baseline 12 weeks after treatment is initiated or as a plasma HIV-1 RNA level that is \>=400 copies/mL at or after 24 weeks of treatment, regardless of whether randomized treatment was being taken at the time of VF.

Outcome measures

Outcome measures
Measure	NVP/NVP n=121 Participants For participants had single dose Nevirapine (SD NVP) exposure prior to study entry, Emtricitabine capsules(FTC) 200mg (1 capsule orally), Tenofovir disproxil fumerate (TDF) 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily in the morning for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive Lopinovir/Ritonovir (LPV/RTV)400/100mg (3 capsules orally) twice daily plus two more Nucleoside reverse transcriptase inhibitors (NRTIs). Following the review on 6 October 2008, the Data Safety Monitoring Board(DSMB) recommended release of the results from this arm.	NVP/LPV_r n=120 Participants For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP 200mg (1 tablet orally) daily for 14 days before taking it twice daily. plus 2 more NRTIs. Following the review on 6 October 2008, the DSMB recommended release of the results from this arm.	NoNVP/NVP n=249 Participants For participants had NO SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally), TDF 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive LPV/RTV 400/100mg (3 capsules orally) twice daily plus two more NRTIs.	NoNVP/LPV_r n=251 Participants For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) once daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP daily 200mg (1 tablet orally) for 14 days before taking it twice daily plus 2 more NRTIs.
Number of Participants Who Experienced Virologic Failure or Died.	32 participants	10 participants	42 participants	50 participants

SECONDARY outcome

Timeframe: Through database cutoff for DSMB review (by October 6, 2008) for NVP/NVP and NVP/LPV_r arms. Throughout study for NoNVP/NVP and NoNVP/LPV_r arms.

Population: Numbers presented use the intent-to-treat approach (i.e. ignoring changes from randomized treatment).

Results report cumulative percent of participants reaching virologic failure (VF) or death by week 48 and week 96 calculated using the Kaplan-Meier method. VF is defined as a plasma HIV-1 RNA level that is 1 log10 below baseline 12 weeks after treatment is initiated or as a plasma HIV-1 RNA level that is \>=400 copies/mL at or after 24 weeks of treatment, regardless of whether randomized treatment was being taken at the time of VF.

Outcome measures

Outcome measures
Measure	NVP/NVP n=121 Participants For participants had single dose Nevirapine (SD NVP) exposure prior to study entry, Emtricitabine capsules(FTC) 200mg (1 capsule orally), Tenofovir disproxil fumerate (TDF) 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily in the morning for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive Lopinovir/Ritonovir (LPV/RTV)400/100mg (3 capsules orally) twice daily plus two more Nucleoside reverse transcriptase inhibitors (NRTIs). Following the review on 6 October 2008, the Data Safety Monitoring Board(DSMB) recommended release of the results from this arm.	NVP/LPV_r n=120 Participants For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP 200mg (1 tablet orally) daily for 14 days before taking it twice daily. plus 2 more NRTIs. Following the review on 6 October 2008, the DSMB recommended release of the results from this arm.	NoNVP/NVP n=249 Participants For participants had NO SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally), TDF 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive LPV/RTV 400/100mg (3 capsules orally) twice daily plus two more NRTIs.	NoNVP/LPV_r n=251 Participants For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) once daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP daily 200mg (1 tablet orally) for 14 days before taking it twice daily plus 2 more NRTIs.
Percent of Participants Who Experienced Virologic Failure or Died week 48 percent of virologic failure or death	23 Percent of participants Interval 16.0 to 31.0	4 Percent of participants Interval 1.0 to 8.0	14 Percent of participants Interval 10.0 to 19.0	14 Percent of participants Interval 9.0 to 18.0
Percent of Participants Who Experienced Virologic Failure or Died week 96 percent of virologic failure or death	31 Percent of participants Interval 21.0 to 40.0	12 Percent of participants Interval 5.0 to 20.0	17 Percent of participants Interval 12.0 to 21.0	20 Percent of participants Interval 14.0 to 25.0

SECONDARY outcome

Timeframe: Through database cutoff for DSMB review (by October 6, 2008) for NVP/NVP and NVP/LPV_r. Throughout study for NoNVP/NVP and NoNVP/LPV_r. Week 48 and 96.

Population: Changes were calculated using the intent-to-treat approach (i.e. ignoring changes from randomized treatment) but no imputation was done for missing values.

Change was calculated as the CD4 count at Week 48 (or at Week 96) minus the baseline CD4 count (last CD4 before/on treatment start date). For NVP/NVP and NVP/LPV\_r arms, data through DSMB review cutoff (October 6, 2008) were used to report the outcome. For NoNVP/NVP and NoNVP/LPV\_r arms, since the follow-up continued as planned, data through overall study were used.

Outcome measures

Outcome measures
Measure	NVP/NVP n=121 Participants For participants had single dose Nevirapine (SD NVP) exposure prior to study entry, Emtricitabine capsules(FTC) 200mg (1 capsule orally), Tenofovir disproxil fumerate (TDF) 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily in the morning for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive Lopinovir/Ritonovir (LPV/RTV)400/100mg (3 capsules orally) twice daily plus two more Nucleoside reverse transcriptase inhibitors (NRTIs). Following the review on 6 October 2008, the Data Safety Monitoring Board(DSMB) recommended release of the results from this arm.	NVP/LPV_r n=120 Participants For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP 200mg (1 tablet orally) daily for 14 days before taking it twice daily. plus 2 more NRTIs. Following the review on 6 October 2008, the DSMB recommended release of the results from this arm.	NoNVP/NVP n=249 Participants For participants had NO SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally), TDF 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive LPV/RTV 400/100mg (3 capsules orally) twice daily plus two more NRTIs.	NoNVP/LPV_r n=251 Participants For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) once daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP daily 200mg (1 tablet orally) for 14 days before taking it twice daily plus 2 more NRTIs.
CD4 Count Change From Randomization Week 48 CD4 count change from randomization	191 cells/mm^3 Interval 120.0 to 270.0	201 cells/mm^3 Interval 142.0 to 280.0	172 cells/mm^3 Interval 97.0 to 246.0	172 cells/mm^3 Interval 97.0 to 268.0
CD4 Count Change From Randomization Week 96 CD4 count change from randomization	291 cells/mm^3 Interval 189.0 to 366.0	278 cells/mm^3 Interval 180.0 to 360.0	223 cells/mm^3 Interval 142.0 to 339.0	256 cells/mm^3 Interval 149.0 to 379.0

SECONDARY outcome

Timeframe: Through database cutoff for DSMB review (by October 6, 2008) for NVP/NVP and NVP/LPV_r. Throughout study for NoNVP/NVP and NoNVP/LPV_r.

Population: Numbers presented use as-treated method.

The outcome is defined as treatment-related toxicity (as evaluated by sites), regardless of grade, that led to discontinuation of randomized regimen. For NVP/NVP and NVP/LPV\_r arms, data through DSMB review cutoff (October 6, 2008) were used to report the outcome. For NoNVP/NVP and NoNVP/LPV\_r arms, since the follow-up continued as planned, data through overall study were used.

Outcome measures

Outcome measures
Measure	NVP/NVP n=121 Participants For participants had single dose Nevirapine (SD NVP) exposure prior to study entry, Emtricitabine capsules(FTC) 200mg (1 capsule orally), Tenofovir disproxil fumerate (TDF) 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily in the morning for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive Lopinovir/Ritonovir (LPV/RTV)400/100mg (3 capsules orally) twice daily plus two more Nucleoside reverse transcriptase inhibitors (NRTIs). Following the review on 6 October 2008, the Data Safety Monitoring Board(DSMB) recommended release of the results from this arm.	NVP/LPV_r n=120 Participants For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP 200mg (1 tablet orally) daily for 14 days before taking it twice daily. plus 2 more NRTIs. Following the review on 6 October 2008, the DSMB recommended release of the results from this arm.	NoNVP/NVP n=249 Participants For participants had NO SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally), TDF 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive LPV/RTV 400/100mg (3 capsules orally) twice daily plus two more NRTIs.	NoNVP/LPV_r n=251 Participants For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) once daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP daily 200mg (1 tablet orally) for 14 days before taking it twice daily plus 2 more NRTIs.
Number of Participants Who Experienced Treatment-related Toxicity That Led to Discontinuation of Randomized Regimen.	15 participants Interval 0.06 to 0.17	0 participants	35 participants Interval 0.09 to 0.18	0 participants

SECONDARY outcome

Timeframe: Through database cutoff for DSMB review (by October 6, 2008) for NVP/NVP and NVP/LPV_r. Throughout study for NoNVP/NVP and NoNVP/LPV_r.

Population: Numbers presented use the intent-to-treat approach (i.e. ignoring changes from randomized treatment).

Worsening to WHO stage III/IV (among subjects who had WHO stage I/II at baseline) and death were the composite secondary endpoint. WHO Disease Staging System for HIV Infection and Disease in Adults and Adolescents is an approach for use in resource limited settings in studies of progression to symptomatic HIV disease. There are 4 stages of disease staging, 1 being the least severe and 4 being the most severe disease stage based on the HIV related symptoms and diagnoses. Please refer to the following web page for detailed staging criteria: http://www.who.int/docstore/hiv/scaling/anex1.html

Outcome measures

Outcome measures
Measure	NVP/NVP n=121 Participants For participants had single dose Nevirapine (SD NVP) exposure prior to study entry, Emtricitabine capsules(FTC) 200mg (1 capsule orally), Tenofovir disproxil fumerate (TDF) 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily in the morning for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive Lopinovir/Ritonovir (LPV/RTV)400/100mg (3 capsules orally) twice daily plus two more Nucleoside reverse transcriptase inhibitors (NRTIs). Following the review on 6 October 2008, the Data Safety Monitoring Board(DSMB) recommended release of the results from this arm.	NVP/LPV_r n=120 Participants For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP 200mg (1 tablet orally) daily for 14 days before taking it twice daily. plus 2 more NRTIs. Following the review on 6 October 2008, the DSMB recommended release of the results from this arm.	NoNVP/NVP n=249 Participants For participants had NO SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally), TDF 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive LPV/RTV 400/100mg (3 capsules orally) twice daily plus two more NRTIs.	NoNVP/LPV_r n=251 Participants For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) once daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP daily 200mg (1 tablet orally) for 14 days before taking it twice daily plus 2 more NRTIs.
Number of Participants Who Experienced HIV-related Disease Progression or Death	6 participants Interval 0.01 to 0.09	4 participants Interval 0.01 to 0.07	19 participants Interval 0.04 to 0.11	26 participants Interval 0.05 to 0.11

SECONDARY outcome

Timeframe: Through database cutoff for DSMB review (by October 6, 2008) for NVP/NVP arm. Throughout study for NoNVP/NVP arm.

Population: Numbers presented use the as-treated approach.

Any grade of rash or grade 2+ liver lab abnormality events that were claimed to be NVP associated (definitely, probably, or possibly) by site investigators were evaluated. Grade 2+ liver lab abnormality is defined as aspartate aminotransferase (AST)\>=2.6 x ULN or alanine aminotransferase (ALT)\>=2.6 x ULN.

Outcome measures

Outcome measures
Measure	NVP/NVP n=121 Participants For participants had single dose Nevirapine (SD NVP) exposure prior to study entry, Emtricitabine capsules(FTC) 200mg (1 capsule orally), Tenofovir disproxil fumerate (TDF) 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily in the morning for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive Lopinovir/Ritonovir (LPV/RTV)400/100mg (3 capsules orally) twice daily plus two more Nucleoside reverse transcriptase inhibitors (NRTIs). Following the review on 6 October 2008, the Data Safety Monitoring Board(DSMB) recommended release of the results from this arm.	NVP/LPV_r For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP 200mg (1 tablet orally) daily for 14 days before taking it twice daily. plus 2 more NRTIs. Following the review on 6 October 2008, the DSMB recommended release of the results from this arm.	NoNVP/NVP n=249 Participants For participants had NO SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally), TDF 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive LPV/RTV 400/100mg (3 capsules orally) twice daily plus two more NRTIs.	NoNVP/LPV_r For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) once daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP daily 200mg (1 tablet orally) for 14 days before taking it twice daily plus 2 more NRTIs.
Number of Participants Who Received NVP-containing Regimens at Randomization and Experienced NVP-associated Rash or Grade 2+ Liver Lab Abnormality	20 participants	—	51 participants	—

SECONDARY outcome

Timeframe: Through database cutoff for DSMB review (by October 6, 2008) for NVP/NVP and NVP/LPV_r arms. Throughout study for NoNVP/NVP and NoNVP/LPV_r arms.

Population: Numbers presented use as-treated approach.

Self-reported adherence at week 48 and 96 while participants remained on randomized regimen. Adherence interviews for each antiretroviral drug drug the participant is taking was performed by site personnel every 24 weeks. For NVP/NVP and NVP/LPV\_r arms, data through DSMB review cutoff (October 6, 2008) were used to report the outcome. For NoNVP/NVP and NoNVP/LPV\_r arms, since the follow-up continued as planned, data through overall study were used.

Outcome measures

Outcome measures
Measure	NVP/NVP n=121 Participants For participants had single dose Nevirapine (SD NVP) exposure prior to study entry, Emtricitabine capsules(FTC) 200mg (1 capsule orally), Tenofovir disproxil fumerate (TDF) 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily in the morning for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive Lopinovir/Ritonovir (LPV/RTV)400/100mg (3 capsules orally) twice daily plus two more Nucleoside reverse transcriptase inhibitors (NRTIs). Following the review on 6 October 2008, the Data Safety Monitoring Board(DSMB) recommended release of the results from this arm.	NVP/LPV_r n=120 Participants For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP 200mg (1 tablet orally) daily for 14 days before taking it twice daily. plus 2 more NRTIs. Following the review on 6 October 2008, the DSMB recommended release of the results from this arm.	NoNVP/NVP n=249 Participants For participants had NO SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally), TDF 300mg (1 tablet orally), and NVP 200mg (1 tablet orally) once daily for the first 14 days, then twice daily after 14 days. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive LPV/RTV 400/100mg (3 capsules orally) twice daily plus two more NRTIs.	NoNVP/LPV_r n=251 Participants For participants had SD NVP exposure prior to study entry, FTC 200mg (1 capsule orally) and TDF 300mg (1 tablet orally) once daily and LPV/RTV 400/100mg (3 capsules orally) twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP daily 200mg (1 tablet orally) for 14 days before taking it twice daily plus 2 more NRTIs.
Percent of Participants Who Reported to Never Missed Any of the Study Drug Regimen in the Past Month week 48 percent of full adherence in past month	89 percent of participants	88 percent of participants	90 percent of participants	86 percent of participants
Percent of Participants Who Reported to Never Missed Any of the Study Drug Regimen in the Past Month week 96 percent of full adherence in past month	94 percent of participants	95 percent of participants	93 percent of participants	87 percent of participants

Adverse Events

NVP/NVP

Serious events: 9 serious events

Other events: 110 other events

Deaths: 0 deaths

NVP/LPV_r

Serious events: 6 serious events

Other events: 105 other events

Deaths: 0 deaths

NoNVP/NVP

Serious events: 26 serious events

Other events: 225 other events

Deaths: 0 deaths

NoNVP/LPV_r

Serious events: 19 serious events

Other events: 227 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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 Trial 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