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Anti-HIV Drug Regimens and Treatment-Switching Guidelines in HIV Infected Children

This study has been completed.
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
PENTA Foundation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00039741
First received: June 7, 2002
Last updated: October 26, 2015
Last verified: November 2014
Results First Received: December 19, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Factorial Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: NRTIs (ABC, FTC, FTC/TDF, 3TC, 3TC/AZT, d4T, TDF, ddC, AZT)
Drug: NNRTIs (EFV, NVP)
Drug: PIs (AMP, IDV, LPV/r, NFV, SQV, RTV)

  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
Recruited at Pediatric AIDS Clinical Trials Group (PACTG) units in the U.S. and Puerto Rico, and Paediatric European Network for Treatment of AIDS (PENTA) units in Argentina, Austria, the Bahamas, Brazil, France, Germany, Italy, Romania, Spain, the United Kingdom and Ireland. Enrollment started 9/25/02 and ended 9/7/05.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were stratified by age (<3 years versus 3+ years), origin (PACTG site or PENTA site), and exposure versus no exposure to antiretroviral therapy perinatally. 266 children were randomized, of whom 3 are excluded from all analyses (2 had consent withdrawn by parents after randomization, 1 was ineligible).

Reporting Groups
  Description
PI/1K Two nucleoside reverse transcriptase inhibitors (NRTI) plus a protease inhibitor (PI)with a regimen change recommended when viral load is 1000 copies/ml or higher
NNRTI/1K 2 NRTIs plus a nonnucleoside reverse transcriptase inhibitor (NNRTI) with a regimen change recommended when viral load reaches 1,000 copies/ml or higher
PI/30K Two NRTIs plus a PIwith a regimen change recommended when viral load is 30,000 copies/ml or higher
NNRTI/30K 2 NRTIs plus an NNRTI with a regimen change recommended when viral load reaches 30,000 copies/ml or higher

Participant Flow:   Overall Study
    PI/1K   NNRTI/1K   PI/30K   NNRTI/30K
STARTED   66   68   65   64 
Death   0   1   0   0 
COMPLETED   51   56   54   50 
NOT COMPLETED   15   12   11   14 
Death                0                1                0                0 
Lost to Follow-up                3                1                5                2 
Confounding medical condition                1                0                0                0 
Not able to get to clinic                5                2                0                3 
Moved                3                2                3                6 
Non-compliance with protocol                1                0                1                0 
Withdrew consent                0                5                0                1 
Missed final visit                2                1                2                2 



  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
PI/1K Two nucleoside reverse transcriptase inhibitors (NRTI) plus a protease inhibitor (PI)with a regimen change recommended when viral load is 1000 copies/ml or higher
NNRTI/1K 2 NRTIs plus a nonnucleoside reverse transcriptase inhibitor (NNRTI) with a regimen change recommended when viral load reaches 1,000 copies/ml or higher
PI/30K Two NRTIs plus a PIwith a regimen change recommended when viral load is 30,000 copies/ml or higher
NNRTI/30K 2 NRTIs plus an NNRTI with a regimen change recommended when viral load reaches 30,000 copies/ml or higher
Total Total of all reporting groups

Baseline Measures
   PI/1K   NNRTI/1K   PI/30K   NNRTI/30K   Total 
Overall Participants Analyzed 
[Units: Participants]
 66   68   65   64   263 
Age 
[Units: Years]
Mean (Standard Deviation)
 8.0  (5.7)   7.0  (5.4)   7.9  (5.4)   6.9  (5.0)   7.5  (5.4) 
Age, Customized 
[Units: Participants]
         
>30 days to <=12 months   10   12   7   11   40 
>12 months to <=3 years   8   7   8   5   28 
>3 to <=9 years   19   27   24   29   99 
>9 to <=14 years   14   13   13   10   50 
>14 years to <18 years   15   9   13   9   46 
Gender 
[Units: Participants]
         
Female   30   33   32   32   127 
Male   36   35   33   32   136 
Region of Enrollment [1] 
[Units: Participants]
         
United States   18   20   16   18   72 
Puerto Rico   1   1   1   0   3 
Argentina   1   4   3   3   11 
Austria   1   0   0   1   2 
Bahamas   2   0   2   0   4 
Brazil   12   11   9   9   41 
France   3   3   5   6   17 
Germany   5   6   3   7   21 
Italy   7   4   5   6   22 
Romania   8   7   9   7   31 
Spain   1   0   1   0   2 
United Kingdom   7   11   9   6   33 
Ireland   0   1   2   1   4 
[1] Sites in the US and Puerto Rico were enrolled through PACTG, and other sites were enrolled through PENTA
Viral Load [1] 
[Units: Log10 copies/ml]
Mean (Standard Deviation)
 5.2  (0.8)   5.0  (0.8)   5.0  (0.8)   5.1  (0.8)   5.1  (0.8) 
[1] Log10 HIV-1 RNA (copies/ml)
PENTA/PACTG site 
[Units: Participants]
         
PENTA   47   47   48   46   188 
PACTG   19   21   17   18   75 
CD4 percent (percentage of total lymphocytes that are CD4 cells) 
[Units: CD4%]
Mean (Standard Deviation)
 18  (12)   18  (10)   18  (11)   17  (12)   18  (11) 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change in Viral Load Measured in log10 HIV-1 RNA Copies/ml   [ Time Frame: Baseline visit and 4 years after Study Entry ]

2.  Secondary:   Rate of Grade 3 or Higher Signs, Symptoms, or Laboratory Abnormalities Experienced   [ Time Frame: Up to 6 yrs. (average 4.85 yrs.) ]

3.  Secondary:   Participants With Significant HIV-related Clinical Events, Defined as CDC Category C (AIDS Defining) Diagnoses (Except for Recurrent Bacterial Infections)or Death   [ Time Frame: Up to 6 yrs. (average 4.85 yrs.) ]

4.  Secondary:   Time to Switching to an Alternative Class ART Regimen (Based on Initial Randomized Regimen)   [ Time Frame: Up to 6 yrs. (average 4.85 yrs.) ]

5.  Secondary:   Time to HIV-1 RNA of 400 Copies/ml or Greater During First-line Therapy or Permanent Discontinuation of First-line Therapy   [ Time Frame: Up to 6 yrs. (average 4.85 yrs.) ]

6.  Secondary:   Time to HIV-1 RNA of 30,000 Copies/ml or Greater During Second-line Therapy or Permanent Discontinuation of Second-line Therapy   [ Time Frame: Up to 6 yrs. (average 4.85 yrs.) ]

7.  Secondary:   Number of Children With an HIV-1 RNA Level Less Than 400 Copies/ml Regardless of Therapy at Week 204   [ Time Frame: Week 204 ]

8.  Secondary:   Change in CD4% From Randomization to 4 Years   [ Time Frame: Randomization to 4 years ]

9.  Secondary:   Number of Children With HIV-1 RNA Less Than 400 Copies/ml and on Original Randomized Therapy at 24 Weeks   [ Time Frame: 24 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
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.


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:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00039741     History of Changes
Other Study ID Numbers: P390
PENPACT-1B
10106 ( Registry Identifier: DAIDS ES )
PENTA 9/PACTG 390
Study First Received: June 7, 2002
Results First Received: December 19, 2011
Last Updated: October 26, 2015
Health Authority: United States: Food and Drug Administration