Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Prospective Evaluation of Anti-retroviral Combinations for Treatment Naive, HIV Infected Persons in Resource-limited Settings (PEARLS)

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00084136
First received: June 7, 2004
Last updated: August 10, 2011
Last verified: August 2011
Results First Received: July 13, 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: Atazanavir
Drug: Didanosine (enteric-coated)
Drug: Efavirenz
Drug: Emtricitabine
Drug: Emtricitabine/Tenofovir disoproxil fumarate
Drug: Lamivudine/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 43 sites from 9 countries: 28 in the US, 4 in India, 2 each in Brazil, Malawi, Peru and South Africa, and 1 each in Haiti, Thailand and Zimbabwe, between May 2005 to August 2007.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
HIV-infected, treatment-naive men and women, at least 18 years of age with CD4+ count <300 cells/mm^3.

Reporting Groups
  Description
ZDV/3TC+EFV ZDV/3TC+EFV participants will receive lamivudine/zidovudine and efavirenz
ddI+FTC+ATV

ddI+FTC+ATV participants will receive emtricitabine, atazanavir, and enteric-coated didanosine >

> On May 23, 2008, Arm B was closed following a planned interim review by the study's independent Data and Safety Monitoring Board (DSMB). The DSMB recommendation was based upon compelling evidence that Arm B had significantly more virologic failure (and therefore was inferior when) compared to Arm A. Participants still receiving Arm B medications were offered alternatives, and all participants continued to be followed.

TDF/FTC+EFV TDF/FTC+EFV participants will receive emtricitabine/tenofovir disoproxil fumarate and efavirenz

Participant Flow for 2 periods

Period 1:   PI Comparison
    ZDV/3TC+EFV     ddI+FTC+ATV     TDF/FTC+EFV  
STARTED     519     526     0  
COMPLETED     464 [1]   479 [1]   0  
NOT COMPLETED     55     47     0  
Death                 10                 9                 0  
Lost to Follow-up                 11                 8                 0  
Withdrawal by Subject                 33                 30                 0  
Clinic site closed                 1                 0                 0  
[1] Follow-up was until ddI+FTC+ATV arm was closed per DSMB recommendation on May 23, 2008.

Period 2:   NRTI Comparison
    ZDV/3TC+EFV     ddI+FTC+ATV     TDF/FTC+EFV  
STARTED     519     0     526  
COMPLETED     418 [1]   0     444 [1]
NOT COMPLETED     101     0     82  
Death                 20                 0                 18  
Lost to Follow-up                 14                 0                 12  
Withdrawal by Subject                 54                 0                 38  
Clinic site closed                 12                 0                 14  
Not reason above                 1                 0                 0  
[1] Follow-up though study closeout period (final visit between April 1 and May 31, 2010).



  Baseline Characteristics


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time to Treatment Failure (PI Comparison)   [ Time Frame: Virologic failure starting 14 weeks following randomization; disease progression starting 12 weeks following randomization; and death occurring at any time following randomization. Follow-up until ddI+FTC+ATV arm closed (May 22, 2008). ]

2.  Primary:   Time to Treatment Failure (NRTI Comparison)   [ Time Frame: Virologic failure starting 14 weeks following randomization; disease progression starting 12 weeks following randomization; and death occurring at any time following randomization. Follow-up through study closure (May 31, 2010). ]

3.  Secondary:   Time to Discontinuation of Initial Antiretroviral (ARV) Therapy (PI Comparison)   [ Time Frame: Throughout follow-up until ddI+FTC+ATV arm closed (May 22,2008) ]

4.  Secondary:   Time to Immunologic Failure (PI Comparison)   [ Time Frame: At or after Week 48 (including only follow-up until ddI+FTV+ATV arm closed - May 22,2008) ]

5.  Secondary:   Change in CD4 Count From Screening to Weeks 24, 48, 96 (PI Comparison)   [ Time Frame: weeks 24, 48 and 96 (including follow-up until ddI+FTC+ARV arm closed - May 22, 2008) ]

6.  Secondary:   Time to First Dose Modification or Grade 3 or 4 Adverse Event (PI Comparison)   [ Time Frame: Throughout study follow-up until ddI+FTC+ATV arm closed (May 22, 2008) ]

7.  Secondary:   Plasma HIV-1 Viral Load Fewer Than 400 Copies/ml (PI Comparison)   [ Time Frame: At Weeks 24 and 48 (including only follow-up until ddI+FTC+ARV arm closed - May 22, 2008) ]

8.  Secondary:   Time to Loss of Virologic Response by Week 48 (Defined by FDA TLOVR Algorithm - Excluding Study Allowed ARV Substitutions)(PI Comparison)   [ Time Frame: Week 48 (using follow-up only until closing of ddI+FTV+ATV arm on May 22,2008) ]

9.  Secondary:   Time to Loss of Virologic Response at Week 48 (Defined by FDA TLOVR Algorithm - Including All ARV Substitutions)(PI Comparison)   [ Time Frame: Week 48 (using follow-up only until closing of ddI+FTV+ATV arm on May 22,2008) ]

10.  Secondary:   Time to Discontinuation of Initial Antiretroviral (ARV) Therapy (NRTI Comparison)   [ Time Frame: Throughout follow-up until study closed (May 31,2010) ]

11.  Secondary:   Time to Immunologic Failure (NRTI Comparison)   [ Time Frame: At or after Week 48 (including all follow-up through study closure - May 31,2010) ]

12.  Secondary:   Change in CD4 Count From Screening to Weeks 24, 48, 96 (NRTI Comparison)   [ Time Frame: weeks 24, 48 and 96 (including all follow-up through to study closure on May 31, 2010) ]

13.  Secondary:   Plasma HIV-1 Viral Load Fewer Than 400 Copies/ml (NRTI Comparison)   [ Time Frame: At Weeks 24 and 48 (including follow-up through to study closure on May 31, 2010) ]

14.  Secondary:   Time to Loss of Virologic Response at Week 48 (Defined by FDA TLOVR Algorithm - Excluding Study Allowed ARV Substitutions)(NRTI Comparison)   [ Time Frame: Week 48 (using follow-up through study closure on May 31,2010) ]

15.  Secondary:   Time to Loss of Virologic Response at Week 96 (Defined by FDA TLOVR Algorithm - Excluding Study Allowed ARV Substitutions)(NRTI Comparison)   [ Time Frame: Week 96 (using follow-up through to study closure on May 31,2010) ]

16.  Secondary:   Time to Loss of Virologic Response at Week 48 (Defined by FDA TLOVR Algorithm - Including All ARV Substitutions)(NRTI Comparison)   [ Time Frame: Week 48 using follow-up through study closure on May 31,2010 ]

17.  Secondary:   Time to Loss of Virologic Response at Week 96 (Defined by FDA TLOVR Algorithm - Including All ARV Substitutions)(NRTI Comparison)   [ Time Frame: Week 96 using follow-up through study closure on May 31,2010 ]

18.  Secondary:   Time to First Dose Modification or Grade 3 or 4 Adverse Event (NRTI Comparison)   [ Time Frame: Throughout study follow-up until study closure (May 31, 2010) ]


  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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