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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00089505
First received: August 5, 2004
Last updated: May 10, 2011
Last verified: May 2011
Results First Received: August 30, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: Emtricitabine
Drug: Emtricitabine/Tenofovir disoproxil fumarate
Drug: Lopinavir/Ritonavir
Drug: Nevirapine
Drug: Tenofovir disoproxil fumarate

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
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.

Participant Flow:   Overall Study
    NVP/NVP     NVP/LPV_r     NoNVP/NVP     NoNVP/LPV_r  
STARTED     121 [1]   120     249 [1]   251  
COMPLETED     112 [2]   118 [3]   228     230  
NOT COMPLETED     9     2     21     21  
Death                 4                 1                 5                 8  
Withdrawal by Subject                 3                 0                 6                 6  
Lost to Follow-up                 1                 1                 9                 7  
Physician Decision                 1                 0                 0                 0  
Protocol Violation                 0                 0                 1                 0  
[1] 2 women never started treatment and per protocol, were not followed and not included in analysis.
[2] The results for NVP/NVP were through database cutoff for DSMB review (by 6 October 2008).
[3] The results for NVP/LPV_r were through database cutoff for DSMB review (by 6 October 2008).



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.
Total Total of all reporting groups

Baseline Measures
    NVP/NVP     NVP/LPV_r     NoNVP/NVP     NoNVP/LPV_r     Total  
Number of Participants  
[units: participants]
  121     120     249     251     741  
Age  
[units: years]
Mean ± Standard Deviation
  30  ± 5     31  ± 5     35  ± 7     35  ± 8     33  ± 7  
Age, Customized  
[units: participants]
         
Between 13 and 19 years     0     0     0     2     2  
Between 20 and 29 years     56     49     63     64     232  
Between 30 and 39 years     59     62     125     124     370  
Between 40 and 49 years     5     9     54     49     117  
>=50 years     1     0     7     12     20  
Gender  
[units: participants]
         
Female     121     120     249     251     741  
Male     0     0     0     0     0  
Region of Enrollment  
[units: participants]
         
Kenya     21     23     45     48     137  
Zambia     12     12     19     21     64  
Botswana     13     12     33     30     88  
Uganda     8     9     22     21     60  
Malawi     14     10     22     22     68  
South Africa     35     36     69     67     207  
Zimbabwe     18     18     39     42     117  
CD4 count Categorical  
[units: participants]
         
<50 cells/mm^3     14     11     32     36     93  
Between 50 to 99 cells/mm^3     18     23     63     53     157  
Between 100 to 149 cells/mm^3     35     38     65     78     216  
Between 150 to 199 cells/mm^3     37     32     58     57     184  
Between 200 to 249 cells/mm^3     15     12     18     19     64  
Between 250 to 299 cells/mm^3     1     4     9     4     18  
Between 300 to 349 cells/mm^3     1     0     2     2     5  
>=350 cells/mm^3     0     0     2     2     4  
CD4 count Continuous  
[units: cell/mm^3]
Mean ± Standard Deviation
  136  ± 60     135  ± 61     126  ± 68     125  ± 71     129  ± 67  
Baseline HIV-1 RNA Categorial  
[units: participants]
         
Between 400 and 999 copies/mL     0     1     1     2     4  
Between 1000 and 9,999 copies/mL     5     8     18     11     42  
Between 10,000 and 99,999 copies/mL     44     33     81     88     246  
Between 100,000 and 749,999 copies/mL     61     63     123     128     375  
>=750,000 copies/mL     11     15     26     22     74  
HIV-1 RNA Continuous  
[units: log 10 copies/mL]
Median ( Inter-Quartile Range )
  5.2  
  ( 4.3 to 5.8 )  
  5.1  
  ( 4.2 to 5.9 )  
  5.2  
  ( 4.2 to 5.9 )  
  5.2  
  ( 4.3 to 5.8 )  
  5.2  
  ( 4.7 to 5.5 )  
WHO stage [1]
[units: participants]
         
Clinical stage I     44     56     97     93     290  
Clinical stage II     42     38     72     67     219  
Clinical stage III     30     25     73     80     208  
Clinical stage IV     5     1     7     11     24  
[1] World Health Organization (WHO) produced WHO Disease Staging System for HIV Infection and Disease in Adults and Adolescents. It 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
  Hide All Outcome Measures

1.  Primary:   Time From Randomization to Virologic Failure or Death for Participants Who Had SD NVP Exposure Prior to Study Entry   [ Time Frame: Through database cutoff for DSMB review (by October 6, 2008) with median follow-up 72 weeks and range from 0 to 144 weeks. ]

Measure Type Primary
Measure Title Time From Randomization to Virologic Failure or Death for Participants Who Had SD NVP Exposure Prior to Study Entry
Measure Description 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.
Time Frame Through database cutoff for DSMB review (by October 6, 2008) with median follow-up 72 weeks and range from 0 to 144 weeks.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Numbers presented use the intent-to-treat approach (i.e. ignoring changes from randomized treatment).

Reporting Groups
  Description
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.

Measured Values
    NVP/NVP     NVP/LPV_r     NoNVP/NVP     NoNVP/LPV_r  
Number of Participants Analyzed  
[units: participants]
  121     120     0     0  
Time From Randomization to Virologic Failure or Death for Participants Who Had SD NVP Exposure Prior to Study Entry  
[units: weeks]
Number ( 95% Confidence Interval )
       
5th percentile     12  
  ( 6 to 12 )  
  60  
  ( 12 to 84 )  
   
   
   
   
10th percentile     12  
  ( 12 to 24 )  
  84  
  ( 60 to NA ) [1]
   
   
   
   
25th percentile     60  
  ( 24 to NA ) [2]
  NA  
  ( NA to NA ) [3]
   
   
   
   
[1] Not estimable as the upper limit for survival function at all weeks is above 90%
[2] Not estimable as the upper limit for survival function at all weeks is above 75%
[3] Not estimable as the estimates for survival function at all weeks is above 75%


Statistical Analysis 1 for Time From Randomization to Virologic Failure or Death for Participants Who Had SD NVP Exposure Prior to Study Entry
Groups [1] NVP/NVP vs. NVP/LPV_r
Method [2] Regression, Cox
P Value [3] <0.001
Hazard Ratio (HR) [4] 3.69
95% Confidence Interval ( 1.79 to 7.61 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  The model was stratified by screening CD4 strata (<50 vs. >=50 cells/mm^3).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value was not adjusted for multiple interim analyses, but any adjustment would be negligible because Peto-Haybittle spending function was used as a basis for calculating the repeated confidence intervals used in interim monitoring.
[4] Other relevant estimation information:
  The HR is for NVP/NVP vs. NVP/LPV_r.



2.  Primary:   Time From Randomization to Virologic Failure or Death for Participants Without SD NVP Exposure Prior to Study Entry   [ Time Frame: Throughout study with median follow-up 72 weeks and range from 0 to 180 weeks. ]

Measure Type Primary
Measure Title Time From Randomization to Virologic Failure or Death for Participants Without SD NVP Exposure Prior to Study Entry
Measure Description 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.
Time Frame Throughout study with median follow-up 72 weeks and range from 0 to 180 weeks.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis was intent to treat per protocol.

Reporting Groups
  Description
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.

Measured Values
    NVP/NVP     NVP/LPV_r     NoNVP/NVP     NoNVP/LPV_r  
Number of Participants Analyzed  
[units: participants]
  0     0     249     251  
Time From Randomization to Virologic Failure or Death for Participants Without SD NVP Exposure Prior to Study Entry  
[units: weeks]
Number ( 95% Confidence Interval )
       
5th percentile      
   
   
   
  24  
  ( 12 to 24 )  
  12  
  ( 12 to 24 )  
10th percentile      
   
   
   
  36  
  ( 24 to 48 )  
  36  
  ( 12 to 60 )  
25th percentile      
   
   
   
  NA  
  ( 120 to NA ) [1]
  132  
  ( 96 to NA ) [2]
[1] Not estimable as the estimate for survival function at all weeks is above 75%
[2] Not estimable as the upper limit for survival function at all weeks is above 75%


Statistical Analysis 1 for Time From Randomization to Virologic Failure or Death for Participants Without SD NVP Exposure Prior to Study Entry
Groups [1] NoNVP/NVP vs. NoNVP/LPV_r
Non-Inferiority/Equivalence Test [2] Yes
Method [3] Regression, Cox
P Value [4] 0.43
Hazard Ratio (HR) [5] 0.85
95% Confidence Interval ( 0.56 to 1.29 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  NoNVP/NVP regimen will be considered equivalent to the NoNVP/LPV_r regimen if the two-sided 95% confidence interval for the hazard ratio for virologi falure is entirely below 2.0; equivalence will be established if the same confidence interval is entirely within the range 0.5 to 2.0.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  The cox proportional hazard model was stratified by screening CD4 strata (<50 vs. >=50 cells/mm3).
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value is for a test of superiority and was not adjusted for interim analyses, but any adjustment would be negligible because Peto-Haybittle spending function was used as a basis for calculating the repeated confidence intervals used.
[5] Other relevant estimation information:
  The HR is for NoNVP/NVP vs. NoNVP/LPV_r.



3.  Secondary:   Number of Participants Who Experienced Virologic Failure or Died.   [ Time Frame: 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. ]

Measure Type Secondary
Measure Title Number of Participants Who Experienced Virologic Failure or Died.
Measure Description 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.
Time Frame 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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Numbers presented use the intent-to-treat approach (i.e. ignoring changes from randomized treatment).

Reporting Groups
  Description
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.

Measured Values
    NVP/NVP     NVP/LPV_r     NoNVP/NVP     NoNVP/LPV_r  
Number of Participants Analyzed  
[units: participants]
  121     120     249     251  
Number of Participants Who Experienced Virologic Failure or Died.  
[units: participants]
  32     10     42     50  

No statistical analysis provided for Number of Participants Who Experienced Virologic Failure or Died.



4.  Secondary:   Percent of Participants Who Experienced Virologic Failure or Died   [ Time Frame: 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. ]

Measure Type Secondary
Measure Title Percent of Participants Who Experienced Virologic Failure or Died
Measure Description 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.
Time Frame 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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Numbers presented use the intent-to-treat approach (i.e. ignoring changes from randomized treatment).

Reporting Groups
  Description
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.

Measured Values
    NVP/NVP     NVP/LPV_r     NoNVP/NVP     NoNVP/LPV_r  
Number of Participants Analyzed  
[units: participants]
  121     120     249     251  
Percent of Participants Who Experienced Virologic Failure or Died  
[units: Percent of participants]
Number ( 95% Confidence Interval )
       
week 48 percent of virologic failure or death     23  
  ( 16 to 31 )  
  4  
  ( 1 to 8 )  
  14  
  ( 10 to 19 )  
  14  
  ( 9 to 18 )  
week 96 percent of virologic failure or death     31  
  ( 21 to 40 )  
  12  
  ( 5 to 20 )  
  17  
  ( 12 to 21 )  
  20  
  ( 14 to 25 )  

No statistical analysis provided for Percent of Participants Who Experienced Virologic Failure or Died



5.  Secondary:   CD4 Count Change From Randomization   [ Time Frame: 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. ]

Measure Type Secondary
Measure Title CD4 Count Change From Randomization
Measure Description 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.
Time Frame 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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Changes were calculated using the intent-to-treat approach (i.e. ignoring changes from randomized treatment) but no imputation was done for missing values.

Reporting Groups
  Description
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.

Measured Values
    NVP/NVP     NVP/LPV_r     NoNVP/NVP     NoNVP/LPV_r  
Number of Participants Analyzed  
[units: participants]
  121     120     249     251  
CD4 Count Change From Randomization  
[units: cells/mm^3]
Median ( Inter-Quartile Range )
       
Week 48 CD4 count change from randomization     191  
  ( 120 to 270 )  
  201  
  ( 142 to 280 )  
  172  
  ( 97 to 246 )  
  172  
  ( 97 to 268 )  
Week 96 CD4 count change from randomization     291  
  ( 189 to 366 )  
  278  
  ( 180 to 360 )  
  223  
  ( 142 to 339 )  
  256  
  ( 149 to 379 )  

No statistical analysis provided for CD4 Count Change From Randomization



6.  Secondary:   Number of Participants Who Experienced Treatment-related Toxicity That Led to Discontinuation of Randomized Regimen.   [ Time Frame: 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. ]

Measure Type Secondary
Measure Title Number of Participants Who Experienced Treatment-related Toxicity That Led to Discontinuation of Randomized Regimen.
Measure Description 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.
Time Frame 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.  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Numbers presented use as-treated method.

Reporting Groups
  Description
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.

Measured Values
    NVP/NVP     NVP/LPV_r     NoNVP/NVP     NoNVP/LPV_r  
Number of Participants Analyzed  
[units: participants]
  121     120     249     251  
Number of Participants Who Experienced Treatment-related Toxicity That Led to Discontinuation of Randomized Regimen.  
[units: participants]
  15     0     35     0  

No statistical analysis provided for Number of Participants Who Experienced Treatment-related Toxicity That Led to Discontinuation of Randomized Regimen.



7.  Secondary:   Number of Participants Who Experienced HIV-related Disease Progression or Death   [ Time Frame: 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. ]

Measure Type Secondary
Measure Title Number of Participants Who Experienced HIV-related Disease Progression or Death
Measure Description 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
Time Frame 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.  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Numbers presented use the intent-to-treat approach (i.e. ignoring changes from randomized treatment).

Reporting Groups
  Description
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.

Measured Values
    NVP/NVP     NVP/LPV_r     NoNVP/NVP     NoNVP/LPV_r  
Number of Participants Analyzed  
[units: participants]
  121     120     249     251  
Number of Participants Who Experienced HIV-related Disease Progression or Death  
[units: participants]
  6     4     19     26  

No statistical analysis provided for Number of Participants Who Experienced HIV-related Disease Progression or Death



8.  Secondary:   Number of Participants Who Received NVP-containing Regimens at Randomization and Experienced NVP-associated Rash or Grade 2+ Liver Lab Abnormality   [ Time Frame: Through database cutoff for DSMB review (by October 6, 2008) for NVP/NVP arm. Throughout study for NoNVP/NVP arm. ]

Measure Type Secondary
Measure Title Number of Participants Who Received NVP-containing Regimens at Randomization and Experienced NVP-associated Rash or Grade 2+ Liver Lab Abnormality
Measure Description 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.
Time Frame Through database cutoff for DSMB review (by October 6, 2008) for NVP/NVP arm. Throughout study for NoNVP/NVP arm.  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Numbers presented use the as-treated approach.

Reporting Groups
  Description
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.

Measured Values
    NVP/NVP     NVP/LPV_r     NoNVP/NVP     NoNVP/LPV_r  
Number of Participants Analyzed  
[units: participants]
  121     0     249     0  
Number of Participants Who Received NVP-containing Regimens at Randomization and Experienced NVP-associated Rash or Grade 2+ Liver Lab Abnormality  
[units: participants]
  20         51      

No statistical analysis provided for Number of Participants Who Received NVP-containing Regimens at Randomization and Experienced NVP-associated Rash or Grade 2+ Liver Lab Abnormality



9.  Secondary:   Percent of Participants Who Reported to Never Missed Any of the Study Drug Regimen in the Past Month   [ Time Frame: 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. ]

Measure Type Secondary
Measure Title Percent of Participants Who Reported to Never Missed Any of the Study Drug Regimen in the Past Month
Measure Description 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.
Time Frame 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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Numbers presented use as-treated approach.

Reporting Groups
  Description
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.

Measured Values
    NVP/NVP     NVP/LPV_r     NoNVP/NVP     NoNVP/LPV_r  
Number of Participants Analyzed  
[units: participants]
  121     120     249     251  
Percent of Participants Who Reported to Never Missed Any of the Study Drug Regimen in the Past Month  
[units: percent of participants]
       
week 48 percent of full adherence in past month     89     88     90     86  
week 96 percent of full adherence in past month     94     95     93     87  

No statistical analysis provided for Percent of Participants Who Reported to Never Missed Any of the Study Drug Regimen in the Past Month




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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