Immediate ART in Subjects With Opportunistic Diseases

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 by an opportunistic disease in HIV-infected individuals who start immediate versus conventional antiretroviral therapy.

Immediate ART (iART) is defined as starting antiretroviral therapy in the first 48 hours after the hospitalization.

Conventional ART (cART) is defined as starting antiretroviral therapy once the opportunistic infection is under control at the discretion of infectious disease specialist.

Study Overview

• Status: Recruiting
• Conditions: HIV/AIDS; ANTIRETROVIRAL TREATMENT
• Intervention / Treatment: Other: iART; Other: cART

Detailed Description

Sample size was calculated using formula, of difference in proportions formula using a beta of 0.1, alpha of 0.05 and an expected difference in mortality of 20%, The sample size is 225 subjects in each group. Informed consent will be obtained. Patients will be allocated to each group (iART or cART) after randomization stratified by the CD4+ T cell count (less or more than 50 cells/mm3).

Plasma viral load and CD4+ T cell count will be measured at study entry and at weeks 2, 4, 12, 24 and 48 after ART initiation. Clinical outcomes will be: mortality at 4, 12, 24, and 48 weeks, length of hospitalization (measured in days), clinical and microbiological cure of the opportunistic disease, incidence and severity of immune reconstitution of inflammatory syndrome (IRIS), and adverse drug reactions and interactions.

Once 50% of the sample size has completed 30 days of follow-up, a preliminary analysis will be conducted to assess safety and efficacy of iART; if differences in the mortality are observed, the study will be terminated.

• Study Type: Interventional
• Enrollment (Estimated): 114
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: GUSTAVO MD REYES-TERÁN, M.D.; Phone Number: 100 56667985; Email: gustavo.reyesteran@gmail.com
• Study Contact Backup: Name: Amy MD Peralta, M.D.; Phone Number: 100 56667985; Email: amy.peralta@cieni.org.mx

Study Locations

• Mexico
  • Mexico, Mexico, 14080
    • Recruiting
    • Centro de Investigacion en Enfermedades Infecciosas
    • Contact: Gustavo Reyes-Teran, M.D.; Phone Number: +52(55)56667985
    • Contact: Yuria Ablanedo-Terrazas, M.D.; Phone Number: +52(55)56667985
    • Principal Investigator: Gustavo Reyes-Teran, M.D.
    • Sub-Investigator: Amy Bethel Peralta Prado, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Over 18 years old
• Time from admission to study entry: less than 48 hours
• Confirmed HIV diagnosis or high probability of HIV infection based on a positive HIV rapid test
• Having an opportunistic disease
• Subjects must be naïve to ART or have failed their first or second ART regimen or must have abandoned ART for more than 3 months

Exclusion Criteria:

• Meningitis due to Cryptococcus spp. or for M. tuberculosis
• Pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A Immediate treatment (iART); Other: time to start the ART within 48 hours of admission to hospitalization	Other: iART; After group assignment, ART will be started within the first 48 hours after admission to the hospital. ART regimen will be decided according to each subject´s the clinical characteristics
Active Comparator: Group B Conventional treatment (cART); Other: time to start the ART, after the opportunistic disease has been controlled, at the discretion of infectious disease specialist.	Other: cART; After group assignment, ART is started at the discretion of the attending physician. ART regimen will be decided according to each subject´s the clinical characteristics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Compare mortality rates betweeno two groups according to the timing of ART initiation: immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART)	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess survival rates	Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART)	90 days since starting antiretroviral therapy (ART)
Assess survival rates	Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART)	180 days since starting antiretroviral therapy (ART)
Assess survival rates	Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART)	360 days since starting antiretroviral therapy (ART)
Length of stay	Compare length of hospitalization between both groups	1 year
Asses survival rates by the CD4 count	Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART) stratified by CD4+ T cell count at study entry	90 days
Asses survival rates by the CD4 count	Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART) stratified by CD4+ T cell count at study entry	180 days
Asses survival rates by the CD4 count	Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART) stratified by CD4+ T cell count at study entry	360 days
Viral load	Measure the baseline plasma viral load and evaluate its dynamics after ART initiation in both groups	90 days
Viral load	Measure the baseline plasma viral load and evaluate its dynamics after ART initiation in both groups	180 days
Viral load	Measure the baseline plasma viral load and evaluate its dynamics after ART initiation in both groups	360 days
CD4 T cell counts	Measure CD4+ T cell counts, and evaluate its dynamics after ART initiation in both groups	90 days
CD4 T cell counts	Measure CD4+ T cell counts, and evaluate its dynamics after ART initiation in both groups	180 days
CD4 T cell counts	Measure CD4+ T cell counts, and evaluate its dynamics after ART initiation in both groups	360 days
IRIS	Determine the incidence and severity of IRIS. Severity will be classified as mild or life threatening	48 weeks
Adverse reactions	Describe ART-related adverse events, and drug interactions	48 weeks

Collaborators and Investigators

• Sponsor: Gustavo Reyes-Teran
• Investigators: Principal Investigator: GUSTAVO MD REYES-TERÁN, M.D., Instituto Nacional de Enfermedades Respiratorias

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2019
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): April 30, 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): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: HIV/AIDS; ART
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
• 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