Randomised Trial of Structured Treatment Interruption of HAART in HIV-Infected Adults in Abidjan (ANRS 1269 TRIVACAN)

Multicentric Randomised Controlled Trial Assessing the Efficacy of Two Strategies of Structured Treatment Interruption of Highly Active Antiretroviral Therapy (HAART) Compared With a Continuous HAART in HIV- Infected Adults in Abidjan

Interrupting HAART during limited periods of time ("structured treatment interruption : STI") could entail benefits (better long term tolerance, lower drug-induced viral resistance, lower cost) but also concomitant risks (lower efficacy, higher drug-induced viral resistance). At present, the benefit/risk ratio of STI is unclear. Several STI trials are in progress in industrialised countries. This trial aim at assessing the benefits and risks of two different STI strategies in West Africa.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Procedure: Structured Treatment Interruption; Drug: Zidovudine (ZDV); Drug: Lamivudine (3TC); Drug: Efavirenz (EFV); Drug: Ritonavir (NRV); Drug: Indinavir (IDV)

Detailed Description

The objective of this study is to assess the non-inferiority of two strategies of structured treatment interruption (STI) of highly active antiretroviral treatment (HAART) compared with a continuous HAART.

It's a multicentric open labeled randomised non-inferiority trial, which takes place in 5 health care centres in Abidjan, the economic capital city of Cote d'Ivoire

The trial was designed in two phases :

1. Pre-randomisation phase : 840 HAART-naive HIV-infected adults start the following continuous HAART regimen: zidovudine-lamivudine in combination with

   • preferably efavirenz, for HIV-1 infected men, and HIV-1 infected women with an effective contraception and no history of nevirapine-containing p-MTCT (prevention of mother to child transmission);
   • ritonavir-indinavir, for HIV-2 infected patients, women not desiring contraception, and women with a past history of p-MTCT with nevirapine.

2. Trial phase : After at least six months on continuous HAART in the pre-randomisation phase, patients who meet success criteria (CD4 count over 350/mm3, undetectable viral load, absence of current opportunistic infection) are randomised into three arms :

   • Arm 1: Continuous HAART (1 of 6 patients)
   • Arm 2: Fixed STI strategy (3 of 6 patients): immutable periods of 2 months on HAART / 4 months off HAART
   • Arm 3: CD4-guided STI strategy (2 of 6 patients): unlimited interruption of HAART, and then re-introduction/re-interruption guided by the evolution of the CD4 count.

Following the DSMB recommendation, the arm 3 has been discontinued in october 2005. The trial is continuing for patients in the arms 1 and 2.

• Study Type: Interventional
• Enrollment (Actual): 840
• Phase: Phase 3

Contacts and Locations

Study Locations

• Côte D'Ivoire
  • Abidjan, Côte D'Ivoire
    • Centre de Prise en Charge et de Formation ACONDA
  • Abidjan, Côte D'Ivoire
    • Centre de Suivi des donneurs de sang, Centre National de Transfusion Sanguine
  • Abidjan, Côte D'Ivoire
    • Centre Intégré de Recherches Biocliniques d'Abidjan
  • Abidjan, Côte D'Ivoire
    • Service des Maladies Infectieuses et Tropicales, CHU de Treichville
  • Abidjan, Côte D'Ivoire
    • Unité de Soins Ambulatoires et de Conseil, CHU de Treichville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed consent
• 18 years old or more
• CD4 count between 150 and 350 per mm3 (or CD4 percentage between 12.5 and 20 percent)
• no past history of curative antiretroviral therapy
• residence in Abidjan

Exclusion Criteria:

• pregnancy
• severe renal failure
• severe hepatic failure
• severe neuropsychiatric disease

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
To assess the non-inferiority at 24 months of two STI strategies of HAART compared with a continuous HAART in terms of :
Percentage of patients with CD4 count over 350 per mm3
Incidence of severe morbidity
Incidence of mortality

Secondary Outcome Measures

Outcome Measure
To compare at 24 months two STI strategies of HAART with a continuous HAART in terms of :
HIV resistance to antiretroviral drugs
Cost-utility
Compliance to treatment

Collaborators and Investigators

• Sponsor: French National Agency for Research on AIDS and Viral Hepatitis
• Collaborators: Bristol-Myers Squibb
• Investigators: Study Director: Xavier Anglaret, MD, Unité INSERM 593, Université Victor Segalen Bordeaux 2; Principal Investigator: Christine Danel, MD, Programme PACCI, Abidjan; Study Chair: Roger Salamon, Pr, Unité INSERM 593, Université Victor Segalen Bordeaux 2; Study Chair: Emmanuel Bissagnene, Pr, CHU Treichville

Publications and helpful links

General Publications

• Moh R, Danel C, Sorho S, Sauvageot D, Anzian A, Minga A, Gomis OB, Konga C, Inwoley A, Gabillard D, Bissagnene E, Salamon R, Anglaret X. Haematological changes in adults receiving a zidovudine-containing HAART regimen in combination with cotrimoxazole in Cote d'Ivoire. Antivir Ther. 2005;10(5):615-24. doi: 10.1177/135965350501000510.
• Danel C, Moh R, Minga A, Anzian A, Ba-Gomis O, Kanga C, Nzunetu G, Gabillard D, Rouet F, Sorho S, Chaix ML, Eholie S, Menan H, Sauvageot D, Bissagnene E, Salamon R, Anglaret X; Trivacan ANRS 1269 trial group. CD4-guided structured antiretroviral treatment interruption strategy in HIV-infected adults in west Africa (Trivacan ANRS 1269 trial): a randomised trial. Lancet. 2006 Jun 17;367(9527):1981-9. doi: 10.1016/S0140-6736(06)68887-9.
• Danel C, Moh R, Chaix ML, Gabillard D, Gnokoro J, Diby CJ, Toni T, Dohoun L, Rouzioux C, Bissagnene E, Salamon R, Anglaret X; Trivacan ANRS 1269 Trial Group. Two-months-off, four-months-on antiretroviral regimen increases the risk of resistance, compared with continuous therapy: a randomized trial involving West African adults. J Infect Dis. 2009 Jan 1;199(1):66-76. doi: 10.1086/595298.

Study record dates

Study Major Dates

• Study Start: December 1, 2002
• Study Completion (Actual): December 1, 2006

Study Registration Dates

• First Submitted: September 7, 2005
• First Submitted That Met QC Criteria: September 7, 2005
• First Posted (Estimate): September 12, 2005

Study Record Updates

• Last Update Posted (Estimate): December 30, 2008
• Last Update Submitted That Met QC Criteria: December 29, 2008
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: HIV; Treatment Naive; HAART; Treatment Interruption; Structured treatment interruption; Sub-saharian africa
• 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; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Ritonavir; Lamivudine; Zidovudine; Indinavir; Efavirenz
• Other Study ID Numbers: ANRS 1269 TRIVACAN