Completed
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

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What is being tested

Atazanavir

+ Didanosine (enteric-coated)
+ Emtricitabine
Drug
Who is being recruted

Blood-Borne Infections
+11

+ Urogenital Diseases
+ Genital Diseases
Over 18 Years
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 4
Interventional
Study Start: May 2005
See protocol details

Summary

Principal SponsorAdvancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Last updated: January 14, 2026
Sourced from a government-validated database.Claim as a partner
Study start date: May 1, 2005Actual date on which the first participant was enrolled.

In developed countries, standard effective antiretroviral (ARV) therapy for treatment-naive HIV infected people includes three-drug combinations of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). However, direct comparisons of ARV efficacy in persons that more closely reflect the worldwide demographics of HIV-1 infection are needed.> > Trial participants were recruited in Africa (Malawi, South Africa, Zimbabwe), Asia (India, Thailand), South America (Brazil, Peru), Haiti, and the United States.> > All participants were randomly assigned to one of three arms, and random allocation was stratified by 2 factors: country, and screening plasma HIV-1 RNA level (< 100,000 copies/mL versus >= 100,000 copies/mL). Participants assigned to the ZDV/3TC+EFV arm received lamivudine/zidovudine twice daily and efavirenz once daily. Participants assigned to the ddI+FTC+ATV arm received emtricitabine, atazanavir, and enteric-coated didanosine once daily. Participants assigned to the TDF/FTC+EFV arm received emtricitabine, tenofovir disoproxil fumarate, and efavirenz once daily. > > > Physical exam and blood collection occurred at entry and at most study visits. Participants experiencing virologic failure were offered a switch to another regimen. > > On May 23, 2008, the ddI+FTC+ATV 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 this arm had significantly more virologic failure (and therefore was inferior when) compared to the ZDV/3TC+EFV arm . Participants still receiving ddI+FTC+ATV were offered alternative medications, and all participants continued to be followed. > > On November 3, 2009, the DSMB recommended that the study close to all follow-up on May 31, 2010, before the designed termination (based on 30% of participants meeting the primary outcome) was met. The board observed that the recent accumulation of primary efficacy events (i.e. regimen failures) was very slow. Therefore, if the study were to continue another 1-2 years, the precision gained for treatment comparisons would likely be small.

Official TitleRandomized, 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 
NCT00084136
Principal SponsorAdvancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Last updated: January 14, 2026
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
1571 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, participants are placed into groups randomly, like flipping a coin. This ensures that the study is fair and unbiased, making the results more reliable. By assigning participants by chance, researchers can better compare treatments without external influences.

Other Ways to Assign Participants
Non-randomized allocation: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.
None (Single-arm trial): If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
Participants are divided into different groups, each receiving a specific treatment at the same time. This helps researchers compare how well different treatments work against each other.

Other Ways to Assign Treatments
Single-group assignment: Everyone gets the same treatment.
Cross-over assignment: Participants switch between treatments during the study.
Factorial assignment: Participants receive different combinations of treatments.
Sequential assignment: Participants receive treatments one after another in a specific order, possibly based on individual responses.
Other assignment: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind: Participants do not know which treatment they are receiving, but researchers do.
Double-blind: Neither participants nor researchers know which treatment is given.
Triple-blind: Participants, researchers, and outcome assessors do not know which treatment is given.
Quadruple-blind: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 18 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Blood-Borne Infections
Urogenital Diseases
Genital Diseases
Communicable Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Virus Diseases
Sexually Transmitted Diseases, Viral
HIV Infections
Lentivirus Infections
Criteria

Inclusion Criteria :\> * HIV-1 infected\> * CD4 count fewer than 300 cells/mm3 \> * Viral load test result\> * Absolute Neutrophil Count at least 750mm3 \> * Hemoglobin at least 7.5 g/dL\> * Platelet count at least 50,000/mm3\> * Calculated creatinine clearance at least 60 mL/min\> * A , A, and alkaline phosphatase \<= 5 times upper limit of normal\> * total bilirubin \<= 2.5 times upper limit of normal\> * Karnofsky performance score of 70 or higher\> * Plans to stay in the area for the duration of the study\> * Agrees to use acceptable forms of contraception for the duration of the study\> Exclusion Criteria:\> * More than 7 days exposure to ARVs (except for single-dose NVP or ZDV for any period for the purpose of pMTCT)\> * Acute therapy for serious medical illnesses within 14 days prior to study entry\> * Certain abnormal laboratory values\> * Radiation therapy or chemotherapy within 45 days prior to study entry. \> * Any immunomodulator, HIV vaccine, or other investigational therapy within 30 days prior to study entry. \> * Current alcohol or drug abuse that, in the opinion of the site investigator, would interfere with study participation\> * Inflamed pancreas within 3 years prior to study entry\> * Allergy/sensitivity to any of the study drugs or their formulations\> * Heart rate less than 40 beats/min\> * History of untreated, active second- or third-degree heart block\> * Currently detained in jail or for treatment of a psychiatric or physical illness\> * Vomiting or inability to swallow medications\> * Pregnancy\>

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
3 intervention groups 

are designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
ddI+FTC+ATV participants will receive emtricitabine, atazanavir, and enteric-coated didanosine

400 mg taken orally daily

400 mg taken orally daily

200 mg taken orally daily
Group II
Experimental
TDF/FTC+EFV participants will receive emtricitabine/tenofovir disoproxil fumarate and efavirenz

600 mg taken orally daily

200 mg/300 mg taken orally once daily
Group III
Experimental
ZDV/3TC+EFV participants will receive lamivudine/zidovudine and efavirenz

600 mg taken orally daily

150 mg/300 mg taken orally twice daily
Study Objectives
Primary Objectives

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 Immune Reconstitution Inflammatory Syndrome (reviewed by chairs); date of death (due to any cause). Plasma drawn every 8 weeks (except confirmation samples could be drawn earlier).

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 Immune Reconstitution Inflammatory Syndrome (reviewed by chairs); date of death (due to any cause). Plasma drawn every 8 weeks (except confirmation samples could be drawn earlier).
Secondary Objectives

Time is measured from date of treatment initiation to earliest of the following: date of last participant contact (premature discontinuation of study follow-up); date all ARV medications were held (if all medications held for at least 8 weeks, for any reason); date that any ARV medication was changed (excluding the following single ARV substitutions: stavudine or tenofovir for zidovudine, nevirapine for efavirenz, or didanosine for tenofovir).

Time from randomization to the first scheduled study visit (week 48 or later) with a CD4+ cell count fewer than 100 cells/mm3.

Available pre-randomization CD4 cell counts were limited to the single CD4 cell count used for study eligibility (and therefore must have been fewer than 300 cells/mm3).

Time from treatment dispensation to the first occurring of the following: week of first ARV medication change; week of first grade 3 or higher sign/symptom or laboratory abnormality (total bilirubin was excluded) that was at least one grade higher than baseline. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables.

Number of participants with plasma HIV-1 Viral load fewer than 400 copies/mL at study visit weeks 24 and 48. Closest observed result between 20 and up to 28 weeks (for week 24), and between 44 and up to 52 (for week 48) used if multiple results available. Missing values excluded, and both study treatment status and history ignored.

Time from randomization to any of the following events occurring prior to week 48: discontinued ARV regimen (see time to discontinuation of initial ARV therapy above); discontinued study follow-up or died; absence of virologic suppression defined as 2 consecutive plasma HIV-1 RNA values \< 400 copies/mL; two consecutive plasma HIV-1 RNA values \> 400 copies/mL following virologic suppression.

Time from randomization to any of the following events occurring prior to week 48: changed any ARV medication (including permanent discontinuation of all medications); discontinued study follow-up or died; absence of virologic suppression defined as 2 consecutive plasma HIV-1 RNA values \< 400 copies/mL; two consecutive plasma HIV-1 RNA values \> 400 copies/mL following virologic suppression.

Time is measured from date of treatment initiation to earliest of the following: date of last participant contact (premature discontinuation of study follow-up); date all ARV medications were held (if all medications held for at least 8 weeks, for any reason); date that any ARV medication was changed (excluding the following single ARV substitutions: stavudine or tenofovir for zidovudine, nevirapine for efavirenz, or didanosine for tenofovir).

Time from randomization to the first scheduled study visit (week 48 or later) with a CD4+ cell count fewer than 100 cells/mm3.

Available pre-randomization CD4 cell counts were limited to the single CD4 cell count used for study eligibility (and therefore must have been fewer than 300 cells/mm3).

Number of participants with plasma HIV-1 Viral load fewer than 400 copies/mL at study visit weeks 24 and 48. Closest observed result between 20 and up to 28 weeks (for week 24), and between 44 and up to 52 (for week 48) used if multiple results available. Missing values excluded, and both study treatment status and history ignored.

Time from randomization to any of the following events occurring prior to week 48: discontinued ARV regimen (see time to discontinuation of initial ARV therapy above); discontinued study follow-up or died; absence of virologic suppression defined as 2 consecutive plasma HIV-1 RNA values \< 400 copies/mL; two consecutive plasma HIV-1 RNA values \> 400 copies/mL following virologic suppression.

Time from randomization to any of the following events occurring prior to week 96: discontinued ARV regimen (see time to discontinuation of initial ARV therapy above); discontinued study follow-up or died; absence of virologic suppression defined as 2 consecutive plasma HIV-1 RNA values \< 400 copies/mL; two consecutive plasma HIV-1 RNA values \> 400 copies/mL following virologic suppression.

Time from randomization to any of the following events occurring prior to week 48: changed any ARV medication (including permanent discontinuation of all medications); discontinued study follow-up or died; absence of virologic suppression defined as 2 consecutive plasma HIV-1 RNA values \< 400 copies/mL; two consecutive plasma HIV-1 RNA values \> 400 copies/mL following virologic suppression.

Time to any of the following events occurring prior to week 96: changed any ARV medication (including permanent discontinuation of all medications); discontinued study follow-up or died; absence of virologic suppression defined as 2 consecutive plasma HIV-1 RNA values \< 400 copies/mL; two consecutive plasma HIV-1 RNA values \> 400 copies/mL following virologic suppression.

Time from treatment dispensation to the first occurring of the following: week of first ARV medication change; week of first grade 3 or higher sign/symptom or laboratory abnormality (total bilirubin was excluded) that was at least one grade higher than baseline. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 42 locations
Suspended
University of Southern CaliforniaLos Angeles, United StatesSee the location
Suspended
UCLA CARE Center CRSLos Angeles, United States
Suspended
Harbor General/UCLATorrance, United States
Suspended
Univ. of Colorado Health Sciences Center, DenverDenver, United States
Completed42 Study Centers