Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Antiviral Responses to NNRTI-Based vs. PI-Based ARV Therapy in HIV Infected Infants Who Have or Have Not Received Single Dose NVP for Prevention of Mother-to-Child Transmission of HIV (P1060)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00307151
First received: March 24, 2006
Last updated: December 3, 2015
Last verified: December 2015
Results First Received: July 5, 2011  
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: Lamivudine
Drug: Lopinavir/ritonavir
Drug: Nevirapine
Drug: Zidovudine

  Participant Flow
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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 study sites, 4 in South Africa and 1 each in Uganda, Zimbabwe, Zambia, Malawi, Tanzania and India between November 9, 2006 and March 19, 2010.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Infants and children 6 - 36 months of age (lower age limit changed to 2 months in Protocol Version 4.0) were stratified by age (2-<6 months, 6-<12 months and >=12 months) and randomly assigned to receive either AZT/3TC/NVP or AZT/3TC/LPV/r. One subject was randomized but never started study treatment.

Reporting Groups
  Description
Coh I: NVP Cohort I: Previously received single dose nevirapine (SD NVP). Randomly assigned to receive an NNRTI-based regimen.
Coh I: LPV/r Cohort I: Previously received SD NVP. Randomly assigned to receive a PI-based regimen.
Coh II: NVP Cohort II: Did not previously receive SD NVP. Randomly assigned to receive an NNRTI-based regimen
Coh II: LPV/r Cohort II: Did not previously receive SD NVP. Randomly assigned to receive a PI-based regimen

Participant Flow:   Overall Study
    Coh I: NVP   Coh I: LPV/r   Coh II: NVP   Coh II: LPV/r
STARTED   82   82   147   140 [1] 
COMPLETED   71 [2]   75 [2]   127 [3]   129 [3] 
NOT COMPLETED   11   7   20   11 
Death                4                3                10                3 
Severe debilitation, unable to continue                1                0                0                0 
Subject unable to get to clinic                1                0                6                2 
Withdrew consent                0                1                1                3 
Not willing to adhere to study reqs                2                0                2                2 
Clinic unable to contact subject                3                3                1                1 
[1] One participant never started treatment, were not followed and not included in analysis.
[2] Results are through date DSMB closed Cohort I to accrual (April 20, 2009)
[3] Results are through date DSMB recommended Cohort II results be unblinded (October 27, 2010)



  Baseline Characteristics
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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
Coh I: NVP Cohort I: Previously received single dose nevirapine (SD NVP). Randomly assigned to receive an NNRTI-based regimen.
Coh I: LPV/r Cohort I: Previously received SD NVP. Randomly assigned to receive a PI-based regimen.
Coh II: NVP Cohort II: Did not previously receive SD NVP. Randomly assigned to receive an NNRTI-based regimen
Coh II: LPV/r Cohort II: Did not previously receive SD NVP. Randomly assigned to receive a PI-based regimen
Total Total of all reporting groups

Baseline Measures
   Coh I: NVP   Coh I: LPV/r   Coh II: NVP   Coh II: LPV/r   Total 
Overall Participants Analyzed 
[Units: Participants]
 82   82   147   140   451 
Age, Customized 
[Units: Participants]
         
<12 months   60   63   41   36   200 
>=12 months   22   19   106   104   251 
Gender 
[Units: Participants]
         
Female   46   41   78   72   237 
Male   36   41   69   68   214 
Race/Ethnicity, Customized 
[Units: Participants]
         
Black African   81   81   132   134   428 
Coloured   1   1   1   2   5 
Native of India   0   0   12   4   16 
Not available   0   0   2   0   2 
Region of Enrollment 
[Units: Participants]
         
Tanzania   2   0   8   7   17 
Zambia   2   4   14   18   38 
Uganda   1   4   20   20   45 
Malawi   2   0   16   20   38 
South Africa   71   65   41   36   213 
Zimbabwe   4   9   36   35   84 
India   0   0   12   4   16 
Ever breastfed 
[Units: Participants]
         
Yes   15   19   118   115   267 
No   67   63   29   25   184 
Documentation of SD NVP use at birth 
[Units: Participants]
         
Born before NVP available/mother known to have HIV   0   0   116   104   220 
Medical record review   62   63   10   12   147 
Verbal evidence only   20   19   19   22   80 
Found to have received SD NVP   0   0   2   2   4 
WHO Stage [1] 
[Units: Participants]
         
 7   18   29   25   79 
II   23   22   26   27   98 
III   39   38   80   77   234 
IV   13   4   12   11   40 
[1] World Health Organization (WHO) staging system for HIV infection and disease.
HIV-1 RNA 
[Units: Participants]
         
<100,000 copies/ml   6   5   20   27   58 
100,000 - < 750,000 copies/ml   27   34   70   53   184 
>=750,000 copies/ml   49   43   57   60   209 
CD4 Percent 
[Units: Participants]
         
<15 Percent   24   21   73   69   187 
15 Percent - < 25 Percent   37   37   60   54   188 
>= 25 Percent   21   24   13   17   75 
Missing   0   0   1   0   1 
NVP resistance 
[Units: Participants]
         
Yes   7   11   1   4   23 
No   68   62   110   91   331 
Not available   7   9   36   45   97 


  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Percent of Participants With Treatment Failure, Defined as a Confirmed Virologic Failure or Permanent Discontinuation of the Randomized NNRTI or PI Component of Study Treatment   [ Time Frame: Earlier of 24 weeks or date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009; Coh II: October 27, 2010) ]

Measure Type Primary
Measure Title Percent of Participants With Treatment Failure, Defined as a Confirmed Virologic Failure or Permanent Discontinuation of the Randomized NNRTI or PI Component of Study Treatment
Measure Description Treatment failure is defined as a confirmed plasma HIV-1 RNA level that is <1 log10 copies/mL below the study entry value at 12 to 24 weeks after treatment is initiated OR a confirmed plasma HIV-1 RNA level >400 copies/mL at 24 weeks OR permanent discontinuation of the randomized NNRTI or PI component of study treatment at or prior to 24 weeks of treatment for any reason including death. Results report percent of participants reaching a treatment failure endpoint by week 24 calculated using the Kaplan-Meier method.
Time Frame Earlier of 24 weeks or date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009; Coh II: October 27, 2010)  
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.
Analysis uses intent to treat population

Reporting Groups
  Description
Coh I: NVP Cohort I: Previously received single dose nevirapine (SD NVP). Randomly assigned to receive an NNRTI-based regimen.
Coh I: LPV/r Cohort I: Previously received SD NVP. Randomly assigned to receive a PI-based regimen.
Coh II: NVP Cohort II: Did not previously receive SD NVP. Randomly assigned to receive an NNRTI-based regimen
Coh II: LPV/r Cohort II: Did not previously receive SD NVP. Randomly assigned to receive a PI-based regimen

Measured Values
   Coh I: NVP   Coh I: LPV/r   Coh II: NVP   Coh II: LPV/r 
Participants Analyzed 
[Units: Participants]
 82   82   147   140 
Percent of Participants With Treatment Failure, Defined as a Confirmed Virologic Failure or Permanent Discontinuation of the Randomized NNRTI or PI Component of Study Treatment 
[Units: Percent of participants]
 39.6   21.7   40.8   19.3 


Statistical Analysis 1 for Percent of Participants With Treatment Failure, Defined as a Confirmed Virologic Failure or Permanent Discontinuation of the Randomized NNRTI or PI Component of Study Treatment
Groups [1] Coh I: NVP vs. Coh I: LPV/r
Method [2] t-test, 2 sided
P Value [3] 0.015
Risk Difference (RD) [4] 18.6
95% Confidence Interval 3.7 to 33.6
[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:
  Risk difference estimate stratified by age (<12 months vs. >=12 months)and reports rate on NVP arm minus rate on LPV/r arm
[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 not adjusted for multiple interim analyses, but adjustment would be negligible because Peto-Haybittle spending function used as basis for calculating repeated confidence intervals used in interim monitoring.
[4] Other relevant estimation information:
  Endpoint rates with standard errors calculated from Kaplan-Meier curves for each treatment group and age stratum. Differences in week 24 failure proportions by treatment calculated weighted by the inverse of the variance in each age stratum.

Statistical Analysis 2 for Percent of Participants With Treatment Failure, Defined as a Confirmed Virologic Failure or Permanent Discontinuation of the Randomized NNRTI or PI Component of Study Treatment
Groups [1] Coh II: NVP vs. Coh II: LPV/r
Method [2] t-test, 2 sided
P Value [3] <0.001
Risk Difference (RD) [4] 21.5
95% Confidence Interval 11.2 to 31.8
[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:
  Risk difference estimate stratified by age (<12 months vs. >=12 months) and reports rate on NVP arm minus rate on LPV/r arm
[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 not adjusted for multiple interim analyses, but adjustment would be negligible because Peto-Haybittle spending function used as basis for calculating repeated confidence intervals used in interim monitoring.
[4] Other relevant estimation information:
  Endpoint rates with standard errors calculated from Kaplan-Meier curves for each treatment group and age stratum. Differences in week 24 failure proportions by treatment calculated weighted by the inverse of the variance in each age stratum.



2.  Secondary:   Time From Randomization to Treatment Failure, Defined as Virologic Failure or Permanent Discontinuation of the Randomized NNRTI or PI Component of Study Treatment   [ Time Frame: Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 weeks) ]

Measure Type Secondary
Measure Title Time From Randomization to Treatment Failure, Defined as Virologic Failure or Permanent Discontinuation of the Randomized NNRTI or PI Component of Study Treatment
Measure Description Treatment failure is defined as a confirmed plasma HIV-1 RNA level that is <1 log10 copies/mL below the study entry value at 12 to 24 weeks after treatment is initiated OR a confirmed plasma HIV-1 RNA level >400 copies/mL at 24 weeks OR a confirmed viral rebound >4000 copies/mL after week 24 OR permanent discontinuation of the randomized NNRTI or PI component of study treatment for any reason including death.
Time Frame Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 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.
Analysis uses intent to treat population

Reporting Groups
  Description
Coh I: NVP Cohort I: Previously received single dose nevirapine (SD NVP). Randomly assigned to receive an NNRTI-based regimen.
Coh I: LPV/r Cohort I: Previously received SD NVP. Randomly assigned to receive a PI-based regimen.
Coh II: NVP Cohort II: Did not previously receive SD NVP. Randomly assigned to receive an NNRTI-based regimen
Coh II: LPV/r Cohort II: Did not previously receive SD NVP. Randomly assigned to receive a PI-based regimen

Measured Values
   Coh I: NVP   Coh I: LPV/r   Coh II: NVP   Coh II: LPV/r 
Participants Analyzed 
[Units: Participants]
 82   82   147   140 
Time From Randomization to Treatment Failure, Defined as Virologic Failure or Permanent Discontinuation of the Randomized NNRTI or PI Component of Study Treatment 
[Units: Weeks]
Number (95% Confidence Interval)
       
10th percentile   12 
 (4 to 12) 
 4 
 (4 to 16) 
 4 
 (2 to 8) 
 14 
 (8 to 24) 
25th percentile   16 
 (12 to 24) 
 36 [1] 
 (16 to N/A) 
 16 
 (12 to 24) 
 36 
 (24 to 108) 
[1] Not estimable as upper limit for survival function at all weeks is above 75%

No statistical analysis provided for Time From Randomization to Treatment Failure, Defined as Virologic Failure or Permanent Discontinuation of the Randomized NNRTI or PI Component of Study Treatment



3.  Secondary:   Percent of Participants Experiencing Virologic Failure   [ Time Frame: Earlier of 24 weeks or date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009; Coh II: October 27, 2010) ]

Measure Type Secondary
Measure Title Percent of Participants Experiencing Virologic Failure
Measure Description Virologic failure is defined as a confirmed plasma HIV-1 RNA level that is <1 log10 copies/mL below the study entry value at 12 to 24 weeks after treatment is initiated OR a confirmed plasma HIV-1 RNA level >400 copies/mL at 24 weeks OR death on or before 24 weeks. Results report percent of participants reaching a virologic failure endpoint by week 24 calculated using the Kaplan-Meier method.
Time Frame Earlier of 24 weeks or date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009; Coh II: October 27, 2010)  
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.
Analysis uses intent to treat population.

Reporting Groups
  Description
Coh I: NVP Cohort I: Previously received single dose nevirapine (SD NVP). Randomly assigned to receive an NNRTI-based regimen.
Coh I: LPV/r Cohort I: Previously received SD NVP. Randomly assigned to receive a PI-based regimen.
Coh II: NVP Cohort II: Did not previously receive SD NVP. Randomly assigned to receive an NNRTI-based regimen
Coh II: LPV/r Cohort II: Did not previously receive SD NVP. Randomly assigned to receive a PI-based regimen

Measured Values
   Coh I: NVP   Coh I: LPV/r   Coh II: NVP   Coh II: LPV/r 
Participants Analyzed 
[Units: Participants]
 82   82   147   140 
Percent of Participants Experiencing Virologic Failure 
[Units: Percent of participants]
 27.4   10.4   28.6   12.9 

No statistical analysis provided for Percent of Participants Experiencing Virologic Failure



4.  Secondary:   Time From Randomization to Virologic Failure   [ Time Frame: Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 weeks) ]

Measure Type Secondary
Measure Title Time From Randomization to Virologic Failure
Measure Description Virologic failure is defined as the earlier of a confirmed plasma HIV-1 RNA level that is <1 log10 copies/mL below the study entry value at 12 to 24 weeks after treatment is initiated OR a confirmed plasma HIV-1 RNA level >400 copies/mL at 24 weeks OR a confirmed viral rebound >4000 copies/mL after week 24 OR death.
Time Frame Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 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.
Analysis uses intent to treat population

Reporting Groups
  Description
Coh I: NVP Cohort I: Previously received single dose nevirapine (SD NVP). Randomly assigned to receive an NNRTI-based regimen.
Coh I: LPV/r Cohort I: Previously received SD NVP. Randomly assigned to receive a PI-based regimen.
Coh II: NVP Cohort II: Did not previously receive SD NVP. Randomly assigned to receive an NNRTI-based regimen
Coh II: LPV/r Cohort II: Did not previously receive SD NVP. Randomly assigned to receive a PI-based regimen

Measured Values
   Coh I: NVP   Coh I: LPV/r   Coh II: NVP   Coh II: LPV/r 
Participants Analyzed 
[Units: Participants]
 82   82   147   140 
Time From Randomization to Virologic Failure 
[Units: Weeks]
Number (95% Confidence Interval)
       
5th percentile   12 
 (4 to 12) 
 16 
 (2 to 24) 
 12 
 (2 to 16) 
 16 
 (12 to 24) 
10th percentile   12 
 (12 to 24) 
 24 [1] 
 (12 to N/A) 
 16 
 (12 to 24) 
 24 
 (16 to 36) 
[1] Not estimable as upper limit for survival function at all weeks above 90%

No statistical analysis provided for Time From Randomization to Virologic Failure



5.  Secondary:   Time From Start of Study Treatment to First New Grade >=3 Lab Abnormality, Sign or Symptom Occurring on Study Treatment   [ Time Frame: On randomized NNRTI or PI component of study treatment and until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009; Coh II: October 27, 2010) ]

Measure Type Secondary
Measure Title Time From Start of Study Treatment to First New Grade >=3 Lab Abnormality, Sign or Symptom Occurring on Study Treatment
Measure Description Safety events include lab abnormalities, signs or symptoms of grade 3 or higher. Events were graded according to the Division of AIDS Table for Grading Severity of Adult and Pediatric Adverse Events, Version 1.0. Events defined as new if first occurrence was after initiation of study treatment or if severity increased from entry and while on the NNRTI or PI component of study treatment.
Time Frame On randomized NNRTI or PI component of study treatment and until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009; Coh II: October 27, 2010)  
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.
Uses follow-up from start of NVP or LPV/r component of study treatment until component switched or date of DSMB decision to unblind results, whichever occurred first

Reporting Groups
  Description
Coh I: NVP Cohort I: Previously received single dose nevirapine (SD NVP). Randomly assigned to receive an NNRTI-based regimen.
Coh I: LPV/r Cohort I: Previously received SD NVP. Randomly assigned to receive a PI-based regimen.
Coh II: NVP Cohort II: Did not previously receive SD NVP. Randomly assigned to receive an NNRTI-based regimen
Coh II: LPV/r Cohort II: Did not previously receive SD NVP. Randomly assigned to receive a PI-based regimen

Measured Values
   Coh I: NVP   Coh I: LPV/r   Coh II: NVP   Coh II: LPV/r 
Participants Analyzed 
[Units: Participants]
 82   82   147   140 
Time From Start of Study Treatment to First New Grade >=3 Lab Abnormality, Sign or Symptom Occurring on Study Treatment 
[Units: Weeks]
Number (95% Confidence Interval)
       
10th percentile   4 
 (2 to 12) 
 8 
 (2 to 25) 
 3 
 (1 to 4) 
 4 
 (2 to 5) 
25th percentile   24 [1] 
 (12 to N/A) 
 36 
 (14 to 86) 
 4 
 (4 to 6) 
 12 
 (7 to 24) 
[1] Not estimable as upper limit for survival function at all weeks above 75%

No statistical analysis provided for Time From Start of Study Treatment to First New Grade >=3 Lab Abnormality, Sign or Symptom Occurring on Study Treatment



6.  Secondary:   Number of Participants Developing New NRTI, NNRTI or PI-resistant Virus   [ Time Frame: Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 weeks) ]

Measure Type Secondary
Measure Title Number of Participants Developing New NRTI, NNRTI or PI-resistant Virus
Measure Description Numbers of participants developing new NRTI, NNRTI or PI-resistant virus after reaching a virologic failure endpoint
Time Frame Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 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.
Results included for any participant who was a virologic failure as defined in secondary outcome 4 and who had results available at study entry and virologic failure.

Reporting Groups
  Description
Coh I: NVP Cohort I: Previously received single dose nevirapine (SD NVP). Randomly assigned to receive an NNRTI-based regimen.
Coh I: LPV/r Cohort I: Previously received SD NVP. Randomly assigned to receive a PI-based regimen.
Coh II: NVP Cohort II: Did not previously receive SD NVP. Randomly assigned to receive an NNRTI-based regimen
Coh II: LPV/r Cohort II: Did not previously receive SD NVP. Randomly assigned to receive a PI-based regimen

Measured Values
   Coh I: NVP   Coh I: LPV/r   Coh II: NVP   Coh II: LPV/r 
Participants Analyzed 
[Units: Participants]
 19   5   18   7 
Number of Participants Developing New NRTI, NNRTI or PI-resistant Virus 
[Units: Participants]
 16   1   10   4 

No statistical analysis provided for Number of Participants Developing New NRTI, NNRTI or PI-resistant Virus



7.  Secondary:   Change in CD4 Percent From Entry to Week 48   [ Time Frame: 48 weeks if before date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009; Coh II: October 27, 2010) ]

Measure Type Secondary
Measure Title Change in CD4 Percent From Entry to Week 48
Measure Description Change was calculated as CD4 percent at week 48 minus entry CD4 percent (last CD4 percent before randomization date). Only subjects who reached 48 weeks of follow-up before DSMB decisions to unblind each Cohort were included in summary.
Time Frame 48 weeks if before date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009; Coh II: October 27, 2010)  
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.
Analysis uses intent to treat population. Change reported if subject followed at least 48 weeks before DSMB unblinding of results for each Cohort

Reporting Groups
  Description
Coh I: NVP Cohort I: Previously received single dose nevirapine (SD NVP). Randomly assigned to receive an NNRTI-based regimen.
Coh I: LPV/r Cohort I: Previously received SD NVP. Randomly assigned to receive a PI-based regimen.
Coh II: NVP Cohort II: Did not previously receive SD NVP. Randomly assigned to receive an NNRTI-based regimen
Coh II: LPV/r Cohort II: Did not previously receive SD NVP. Randomly assigned to receive a PI-based regimen

Measured Values
   Coh I: NVP   Coh I: LPV/r   Coh II: NVP   Coh II: LPV/r 
Participants Analyzed 
[Units: Participants]
 63   70   109   119 
Change in CD4 Percent From Entry to Week 48 
[Units: Percent of CD4]
Mean (95% Confidence Interval)
 13.9 
 (11.6 to 16.2) 
 12.0 
 (10.3 to 13.7) 
 15.2 
 (13.6 to 16.9) 
 14.3 
 (13.0 to 15.7) 

No statistical analysis provided for Change in CD4 Percent From Entry to Week 48



8.  Secondary:   Time From Randomization to HIV-related Disease Progression or Death   [ Time Frame: Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 weeks) ]

Measure Type Secondary
Measure Title Time From Randomization to HIV-related Disease Progression or Death
Measure Description HIV-related disease progression was defined as progression in WHO clinical stage from stage at entry or death. For subjects in WHO Stage IV at entry, disease progression was defined as death.
Time Frame Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 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.
Analysis uses intent to treat population

Reporting Groups
  Description
Coh I: NVP Cohort I: Previously received single dose nevirapine (SD NVP). Randomly assigned to receive an NNRTI-based regimen.
Coh I: LPV/r Cohort I: Previously received SD NVP. Randomly assigned to receive a PI-based regimen.
Coh II: NVP Cohort II: Did not previously receive SD NVP. Randomly assigned to receive an NNRTI-based regimen
Coh II: LPV/r Cohort II: Did not previously receive SD NVP. Randomly assigned to receive a PI-based regimen

Measured Values
   Coh I: NVP   Coh I: LPV/r   Coh II: NVP   Coh II: LPV/r 
Participants Analyzed 
[Units: Participants]
 82   82   147   140 
Time From Randomization to HIV-related Disease Progression or Death 
[Units: Weeks]
Number (95% Confidence Interval)
       
5th percentile   11 
 (2 to 24) 
 2 
 (2 to 4) 
 8 
 (2 to 24) 
 35 
 (2 to 132) 
10th percentile   17 [1] 
 (5 to N/A) 
 4 
 (2 to 24) 
 35 [2] 
 (8 to N/A) 
 132 [2] 
 (35 to N/A) 
[1] Not estimable as upper limit of survival function at all weeks above 90%
[2] Not estimable as upper limit of survival function at all weeks above 98%

No statistical analysis provided for Time From Randomization to HIV-related Disease Progression or Death



9.  Secondary:   Time From Randomization to Death   [ Time Frame: Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 weeks) ]

Measure Type Secondary
Measure Title Time From Randomization to Death
Measure Description Results report 2nd percentile of time from randomization to death
Time Frame Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 weeks)  
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.
Analysis uses intent to treat population

Reporting Groups
  Description
Coh I: NVP Cohort I: Previously received single dose nevirapine (SD NVP). Randomly assigned to receive an NNRTI-based regimen.
Coh I: LPV/r Cohort I: Previously received SD NVP. Randomly assigned to receive a PI-based regimen.
Coh II: NVP Cohort II: Did not previously receive SD NVP. Randomly assigned to receive an NNRTI-based regimen
Coh II: LPV/r Cohort II: Did not previously receive SD NVP. Randomly assigned to receive a PI-based regimen

Measured Values
   Coh I: NVP   Coh I: LPV/r   Coh II: NVP   Coh II: LPV/r 
Participants Analyzed 
[Units: Participants]
 82   82   147   140 
Time From Randomization to Death 
[Units: Weeks]
Number (95% Confidence Interval)
 11 
 (3 to 68) 
 3 [1] 
 (2 to N/A) 
 2 
 (2 to 12) 
 83 [1] 
 (3 to N/A) 
[1] Not estimable as upper limit for survival function at all weeks above 98%

No statistical analysis provided for Time From Randomization to Death




  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
Accrual to Cohort I was terminated early by the Data Safety Monitoring Committee after enrollment of 164 of the planned 288 subjects.


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