Immediate ART in Subjects With Opportunistic Diseases (TARi)

June 26, 2026 updated by: Gustavo Reyes-Teran

Impact of the Timing of Antiretroviral Therapy Initiation (Immediate Versus Early) on the Mortality Rate of HIV/AIDS Patients Hospitalized With an Opportunistic Disease

The aim of this study is to compare the clinical response and mortality rate due to opportunistic disease in HIV-infected individuals who start immediate versus conventional antiretroviral therapy (ART).

Immediate ART (iART) is defined as starting antiretroviral therapy within the first 48 hours after hospitalization. Conventional ART (cART) is defined as starting antiretroviral therapy once the opportunistic infection is under control at the discretion of the infectious disease specialist.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is an open-label, randomized clinical trial conducted at the Center for Research in Infectious Diseases (CIENI) of the National Institute of Respiratory Diseases "Ismael Cosío Villegas" (INER) in Mexico City. Adults (≥18 years) with confirmed HIV diagnosis and active opportunistic infections or AIDS-related malignancies are eligible. Participants must be ART-naïve or have discontinued ART for at least 3 months. Key exclusions include suspected cryptococcal meningitis, tuberculous meningitis, or cytomegalovirus retinitis.

Sample Size Calculation Sample size was calculated using a difference in proportions formula with 95% confidence level, 90% power, and 5% expected difference between groups. Based on 2022 hospitalization data (145 patients with HIV hospitalized) and a 6.9% mortality rate, assuming a 5% absolute reduction in mortality (from 6.9% to 1.9%) in the experimental group, the initial required sample size was 359 participants. This was adjusted for finite population (n=145), yielding 103 participants. Accounting for an anticipated 10% loss to follow-up, the final sample size was set at 114 participants (57 per group).

Study Procedures

Participants are stratified by CD4+ T-cell count (<50 vs. ≥50 cells/μL) and randomized 1:1 to either:

  • Immediate ART (iART): Initiation of ART within 48 hours of hospital admission
  • Conventional ART (cART): Initiation of ART once the opportunistic infection is controlled, at the discretion of the treating physician.

Follow-up and Assessments

Participants are followed for 48 weeks with visits at days 7, 14, 30, 90, 180, and 365. At each visit, the following are measured:

  • HIV-1 RNA viral load.
  • CD4+ and CD8+ T-cell counts.
  • Inflammatory markers (C-reactive protein, D-dimer).
  • Clinical outcomes (opportunistic infection resolution/recurrence, IRIS, adverse events, mortality).

Primary Outcome All-cause mortality at 30 days from ART initiation.

Secondary Outcomes

  • Mortality at 90, 180, and 360 days.
  • Length of hospital stay.
  • Time to opportunistic infection resolution or recurrence.
  • Incidence and severity of Immune Reconstitution Inflammatory Syndrome (IRIS).
  • Incidence of adverse events Grade 2, 3, and 4.
  • Kinetics of HIV viremia and CD4+ T-cell count

Interim Analysis A planned preliminary analysis will be conducted once 50% of the sample size completed 90 days of follow-up, to assess the safety and efficacy of immediate ART initiation .

Ethics and Registration The study was approved by the INER Research and Ethics Committee (Approval Number C09-18). All participants provided written informed consent.

Study Type

Interventional

Enrollment (Actual)

114

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • State of Mexico
      • México, State of Mexico, Mexico, 14080
        • Centro de Investigacion en Enfermedades Infecciosas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • HIV infection documented by ELISA or rapid test.
  • Age 18 years or older.
  • Hospitalized at the emergency department, intensive care unit, or clinical pulmonology ward of the National Institute of Respiratory Diseases (INER) with clinical criteria of an opportunistic infection or AIDS-related malignancy.
  • Candidate to initiate first ART regimen or presenting with first- or second-line ART failure.
  • ART-naïve or with ART discontinuation for at least 3 months prior to enrollment.

Exclusion Criteria:

  • Diagnosis or clinical symptoms suggestive of cryptococcal meningitis, tuberculous meningitis, or meningitis of any other cause.
  • Pregnant women.
  • Admitted exclusively for treatment of neurosyphilis without any other active opportunistic infection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Immediate Antiretroviral Therapy (iART).
Participants randomized to this arm will initiate antiretroviral therapy (ART) within 48 hours of hospital admission. The regimen will be selected by the treating physician based on clinical guidelines, with preference for second-generation integrase strand transfer inhibitor (INSTI)-based regimens (e.g., bictegravir/emtricitabine/tenofovir alafenamide [BIC/FTC/TAF]), unless contraindicated.
Drug: Antiretroviral Therapy (ART)
Immediate initiation of ART within 48 hours of hospital admission.
Drug: Antiretroviral Therapy (ART)
Deferred initiation of ART, with timing determined by the treating physician based on clinical stability and control of the opportunistic infection.
Active Comparator: Conventional Antiretroviral Therapy (cART).
Participants randomized to this arm will initiate ART once the opportunistic infection is considered controlled by the treating physician, at their discretion. The regimen will be selected by the treating physician based on clinical guidelines, with preference for second-generation INSTI-based regimens (e.g., BIC/FTC/TAF), unless contraindicated.
Drug: Antiretroviral Therapy (ART)
Immediate initiation of ART within 48 hours of hospital admission.
Drug: Antiretroviral Therapy (ART)
Deferred initiation of ART, with timing determined by the treating physician based on clinical stability and control of the opportunistic infection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality at 30 days.
Time Frame: 30 days from ART initiation
Compare all cause mortality within 30 days of antiretroviral therapy (ART) initiation between immediate ART (iART) versus conventional ART (cART).
30 days from ART initiation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality at 90, 180 and 365 days.
Time Frame: 90, 180, 360 days from ART initiation.
Compare all cause mortality at 90, 180 and 365 days of follow-up, assessed from the date of antiretroviral therapy (ART) initiation between immediate ART (iART) versus conventional ART (cART).
90, 180, 360 days from ART initiation.
Length of hospital stay.
Time Frame: From hospital admission to discharge (assessed up to 365 days).
Total number of days from hospital admission to hospital discharge.
From hospital admission to discharge (assessed up to 365 days).
Time to opportunistic infection resolution or recurrence.
Time Frame: Up to 365 days from ART initiation.
Time from ART initiation to clinical resolution of the opportunistic infection or evidence of recurrence, as documented by clinical, radiological, or microbiological criteria.
Up to 365 days from ART initiation.
Incidence and classification of Immune Reconstitution Inflammatory Syndrome (IRIS).
Time Frame: Up to 365 days from ART initiation.
Incidence of IRIS, classified as severe (life-threatening) or non-severe.
Up to 365 days from ART initiation.
Incidence of adverse events Grade 2, 3, and 4.
Time Frame: Up to 365 days from ART initiation.
Incidence of treatment-related adverse events graded as Grade 2 (moderate), Grade 3 (severe), or Grade 4 (life-threatening).
Up to 365 days from ART initiation.
Kinetics of HIV viremia and CD4+ T-cell count.
Time Frame: Baseline, days 7, 14, 30, 90, 180 and 365.
Longitudinal changes in HIV-1 RNA viral load (log10 copies/mL) and absolute CD4+ T-cell count (cells/μL) over time.
Baseline, days 7, 14, 30, 90, 180 and 365.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gustavo Reyes-Teran

Investigators

  • Principal Investigator: Amy B. Peralta-Prado, M.D., Instituto Nacional de Enfermedades Respiratorias

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 29, 2018

Primary Completion (Actual)

August 5, 2025

Study Completion (Actual)

August 5, 2025

Study Registration Dates

First Submitted

January 18, 2019

First Submitted That Met QC Criteria

January 30, 2019

First Posted (Actual)

January 31, 2019

Study Record Updates

Last Update Posted (Actual)

June 30, 2026

Last Update Submitted That Met QC Criteria

June 26, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C09-18

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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