Reducing Mortality in Adults With Advanced HIV Disease (REVIVE)

Phase 3

Recruiting

• Conditions: HIV Disease Progression
• Interventions: Drug: Azithromycin Oral Tablet; Drug: Placebo oral tablet

• Registration Number: NCT05580666
• Lead Sponsor: Population Health Research Institute

Brief Summary

A double blinded, placebo-controlled, multicenter trial to evaluate effectiveness of azithromycin prophylaxis on mortality in advanced HIV.

Detailed Description

All participants in the REVIVE trial will be randomized (1:1) at the time of study entry to receive azithromycin prophylaxis or placebo for 28 days and will be followed for 24 weeks to determine the primary outcome measure. Total follow up duration will be 48 weeks.

Study Timeline

• Study First Submitted: 2022-10-11
• Study First Submitted QC: 2022-10-13
• Study First Posted: 2022-10-14
• Study Start: 2023-05-08
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-24
• Last Update Posted: 2025-04-29
• Primary Completion: 2028-05-31
• Study Completion: 2028-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 8000

Inclusion Criteria

1. Age ≥ 18 years

2. Documented HIV infection

3. CD4 count criteria:

   i. CD4 count ≤ 100 cells/mm3 within past 4 weeks; or

   ii. Documented CD4 nadir ≤ 100 cells/mm3 and complete interruption of ART for ≥ 6 months; or

   iii. Documented CD4 count ≤ 100 cells/mm3 if ART-naive

4. Ability to initiate or re-initiate ART, or switch to an effective ART regimen if failing current therapy, within 4 weeks of enrolment

Exclusion Criteria

1. Contraindications to azithromycin:

   i. Hypersensitivity to azithromycin, erythromycin, or any macrolide antibiotic; or

   ii. Personal or family history of QT-prolongation

2. Severe illness requiring immediate or continued hospitalization (this will be in the judgment of site investigators)

3. Off-label azithromycin prophylaxis or requirement for prolonged (> 7 days) azithromycin (or macrolide) therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oral Azithromycin 250 mg once daily	Azithromycin Oral Tablet	Active Azithromycin tablet
Oral matching placebo, once daily	Placebo oral tablet	Matching placebo tablet

Primary Outcome Measures

Name	Time	Method
All-cause mortality	24 weeks after randomization	All-cause mortality over the first 24 weeks after randomization

Secondary Outcome Measures

Name	Time	Method
All-cause mortality	12 weeks after randomization	All-cause mortality over the first 12 weeks after randomization
Hospitalization	24 weeks after randomization	Hospitalization over the first 24 weeks after randomization
Composite of hospitalization or all-cause mortality	24 weeks after randomization	Composite of hospitalization or all-cause mortality over the first 24 weeks after randomization

Trial Locations

Locations (44)

Centre médical de suivi des donneurs de sang (CMSDS); 🇨🇮 Abidjan, Côte D'Ivoire

Fondation Congolaise pour la Recherche Médicale; 🇨🇬 Brazzaville, Congo

Unité de Soins Ambulatoires et de conseils (USAC); 🇨🇮 Abidjan, Côte D'Ivoire

University of Botswana; 🇧🇼 Gaborone, Botswana

Komfo Anokye Teaching Hospital; 🇬🇭 Kumasi, Ghana

Adama Hospital Medical College; 🇪🇹 Ādama, Ethiopia

Aminu Kano Teaching Hospital; 🇳🇬 Kano, Nigeria

Usmanu Danfodiyo University Teaching Hos; 🇳🇬 Sokoto, Nigeria

Centre Hospitalier Universitaire de Kigali (CHUK); 🇷🇼 Kigali, Rwanda

Federal Medical Center; 🇳🇬 Umuahia, Nigeria

College of Medicine and Allied Health Sciences, University of Sierra Leone; 🇸🇱 Freetown, Sierra Leone

Lilongwe Medical Relief Fund/UNC Project; 🇲🇼 Lilongwe, Malawi

Mbarara Regional Referral hospital; 🇺🇬 Mbarara, Uganda

Kibong'oto Infectious Diseases Hospital; 🇹🇿 Moshi, Tanzania

University of Calabar Teaching Hospital; 🇳🇬 Calabar, Nigeria

University College Hospital; 🇳🇬 Ibadan, Nigeria

National Institute for Medical Research (NIMR); 🇹🇿 Mbeya, Tanzania

The Center for Infectious Disease Research in Zambia (CIDRZ)- George Clinical Research Site; 🇿🇲 Lusaka, Zambia

Centre de Prise en Charge et de Formation; 🇨🇮 Abidjan, Côte D'Ivoire

University of Abuja Teaching Hospital; 🇳🇬 Abuja, Nigeria

University of Uyo Teaching Hospital; 🇳🇬 Uyo, Nigeria

The Center for Infectious Disease Research in Zambia (CIDRZ)-Chawama Clinical Research Site (CRS); 🇿🇲 Lusaka, Zambia

Kilimanjaro Clinical Research Institute; 🇹🇿 Moshi, Tanzania

New Somerset Hospital; 🇿🇦 Cape Town, South Africa

Wits Health Consortium (Pty) Ltd; 🇿🇦 Johannesburg, South Africa

Africa Health Research Institute (AHRI)- Mtubatuba Clinic; 🇿🇦 Mtubatuba, South Africa

Africa Health Research Institute (AHRI)- Somkhele Clinic; 🇿🇦 Mtubatuba, South Africa

Ubuntu Clinic, Site B, Khayelitsha, Wellcome Centre; 🇿🇦 Cape Town, South Africa

Centre Intégré de Recherches Biocliniques d'Abidjan (CIRBA); 🇨🇮 Abidjan, Côte D'Ivoire

Faculty of Medicine, Eduardo Mondlane University; 🇲🇿 Maputo, Mozambique

University of Nigeria Teaching Hospital; 🇳🇬 Enugu, Nigeria

Jos University Teaching Hospital; 🇳🇬 Jos, Nigeria

Lagos University Teaching Hospital; 🇳🇬 Lago, Nigeria

Niger Delta University Teaching Hospital; 🇳🇬 Yenagoa, Nigeria

Desmond Tutu Health Foundation; 🇿🇦 Cape Town, South Africa

Groote Schuur Hospital -New main building, Infectious Disease Clinic G26; 🇿🇦 Cape Town, South Africa

The Aurum Institute; 🇿🇦 Rustenburg, South Africa

Africa Health Research Institute (AHRI)- Nkundusi Clinic; 🇿🇦 Hlabisa, South Africa

Africa Health Research Institute (AHRI)- KwaMsane Clinic; 🇿🇦 Mtubatuba, South Africa

Africa Health Research Institute (AHRI)- Mpukunyoni Clinic; 🇿🇦 Mtubatuba, South Africa

Steve Biko Academic Hospital, University of Pretoria; 🇿🇦 Pretoria, South Africa

Right to Care NPC, Esizayo Division; 🇿🇦 Randburg, South Africa

The Center for Infectious Disease Research in Zambia (CIDRZ)- Matero Clinical Research Site; 🇿🇲 Lusaka, Zambia

Africa Health Research Institute (AHRI)- Hluhluwe Clinic; 🇿🇦 Hluhluwe, South Africa