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:
Information provided by (Responsible Party):
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00307151
First received: March 24, 2006
Last updated: October 8, 2014
Last verified: October 2014
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  
Number of Participants  
[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  
Study-Specific Measure  
[units: participants]
         
Yes     15     19     118     115     267  
No     67     63     29     25     184  
Study-Specific Measure  
[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  
Study-Specific Measure [1]
[units: participants]
         
I     7     18     29     25     79  
II     23     22     26     27     98  
III     39     38     80     77     234  
IV     13     4     12     11     40  
Study-Specific Measure  
[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  
Study-Specific Measure  
[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  
Study-Specific Measure  
[units: participants]
         
Yes     7     11     1     4     23  
No     68     62     110     91     331  
Not available     7     9     36     45     97  
[1] World Health Organization (WHO) staging system for HIV infection and disease.



  Outcome Measures
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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) ]
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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  
Number of 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) ]

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) ]

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) ]

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) ]

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) ]

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) ]

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) ]

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) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinicaltrials.gov Coordinator
Organization: Center for Biostatistics in AIDS Research, Harvard School of Public Health
phone: (617) 432-2829
e-mail: CBAR.ClinicalTrials.Gov@sdac.harvard.edu


Publications of Results:
Other Publications:

Publications automatically indexed to this study:

Responsible Party: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00307151     History of Changes
Other Study ID Numbers: IMPAACT P1060, U01AI068632
Study First Received: March 24, 2006
Results First Received: July 5, 2011
Last Updated: October 8, 2014
Health Authority: United States: Federal Government