NCT00084136: PEARLS

Randomized, Open-Label Evaluation of Efficacy of Once-Daily Protease Inhibitor and Once-Daily Non-Nucleoside Reverse Transcriptase Inhibitor-Containing Therapy Combinations for Initial Treatment of HIV-1 Infected Persons From Resource-Limited Settings (PEARLS) Trial

Completed Phase 4 Results posted Last updated 11 September 2018

What this trial tests

Phase 4 trial testing Atazanavir in HIV Infections in 1,571 participants. Completed in 1 May 2010.

Timeline

1 May 2005

Primary endpoint
1 May 2010

1 May 2010

Quick facts

Lead sponsor	Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	1,571
Start date	1 May 2005
Primary completion	1 May 2010
Estimated completion	1 May 2010
Sites	42 locations across United States, Brazil, Haiti, India, Malawi, Peru, South Africa, Thailand

Drugs / interventions tested

• Atazanavir (ATAZANAVIR) — full drug profile →
• Didanosine (enteric-coated) — full drug profile →
• Efavirenz (EFAVIRENZ) — full drug profile →
• Emtricitabine (EMTRICITABINE) — full drug profile →
• Emtricitabine/Tenofovir disoproxil fumarate — full drug profile →
• Lamivudine/Zidovudine

Conditions studied

• HIV Infections — all drugs for HIV Infections →

Sponsor

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

Who can join

18 and older, any sex, with HIV Infections. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• 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).
  Time from randomization to the earliest of: scheduled week of first plasma sample meeting virologic failure (two consecutive plasma HIV-1 RNA values 1,000 copies/mL or higher, regardless of whether ARV medications being taken at the time); scheduled week of first AIDS defining diagnosis (WHO Stage 4 (2005), plus microsporidiosis, cyclospora gastroenteritis and Chaga's disease), not attributed to I
• 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).
  Time from randomization to the earliest of: scheduled week of first plasma sample meeting virologic failure (two consecutive plasma HIV-1 RNA values 1,000 copies/mL or higher, regardless of whether ARV medications being taken at the time); scheduled week of first AIDS defining diagnosis (WHO Stage 4 (2005) plus microsporidiosis, cyclospora gastroenteritis and Chaga's disease), not attributed to Im

Sponsor's own description

This study compared 3 different three-drug combinations in HIV infected individuals starting their first HIV treatment regimens. Participants were recruited from resource-limited areas in Africa, Asia, South America, Haiti, and also from the United States. The study hypothesis was each of the once daily combinations (PI based, or NNRTI based) would not have inferior efficacy compared to the twice daily NNRTI based combination.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Association between efavirenz as initial therapy for HIV-1 infection and increased risk for suicidal ideation or attempted or completed suicide: an analysis of trial data.
   Mollan KR, Smurzynski M, Eron JJ, Daar ES, et al · · 2014 · cited 152× · PMID 24979445 · DOI 10.7326/m14-0293
2. Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings.
   Campbell TB, Smeaton LM, Kumarasamy N, Flanigan T, et al · · 2012 · cited 106× · PMID 22936892 · DOI 10.1371/journal.pmed.1001290
3. Pretreatment HIV Drug Resistance and HIV-1 Subtype C Are Independently Associated With Virologic Failure: Results From the Multinational PEARLS (ACTG A5175) Clinical Trial.
   Kantor R, Smeaton L, Vardhanabhuti S, Hudelson SE, et al · · 2015 · cited 68× · PMID 25681380 · DOI 10.1093/cid/civ102
4. Sex-Related Differences in Inflammatory and Immune Activation Markers Before and After Combined Antiretroviral Therapy Initiation.
   Mathad JS, Gupte N, Balagopal A, Asmuth D, et al · · 2016 · cited 65× · PMID 27258230 · DOI 10.1097/qai.0000000000001095
5. Inflammation and Change in Body Weight With Antiretroviral Therapy Initiation in a Multinational Cohort of HIV-Infected Adults.
   Mave V, Erlandson KM, Gupte N, Balagopal A, et al · · 2016 · cited 65× · PMID 26962236 · DOI 10.1093/infdis/jiw096
6. Improved neuropsychological and neurological functioning across three antiretroviral regimens in diverse resource-limited settings: AIDS Clinical Trials Group study a5199, the International Neurological Study.
   Robertson K, Jiang H, Kumwenda J, Supparatpinyo K, et al · · 2012 · cited 54× · PMID 22661489 · DOI 10.1093/cid/cis507
7. Comparisons of anemia, thrombocytopenia, and neutropenia at initiation of HIV antiretroviral therapy in Africa, Asia, and the Americas.
   Firnhaber C, Smeaton L, Saukila N, Flanigan T, et al · · 2010 · cited 54× · PMID 20961784 · DOI 10.1016/j.ijid.2010.08.002
8. Psychosocial predictors of non-adherence and treatment failure in a large scale multi-national trial of antiretroviral therapy for HIV: data from the ACTG A5175/PEARLS trial.
   Safren SA, Biello KB, Smeaton L, Mimiaga MJ, et al · · 2014 · cited 46× · PMID 25153084 · DOI 10.1371/journal.pone.0104178