Immediate ART in Subjects With Opportunistic Diseases

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.

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.