Clinical trial NCT00158405: Randomised Trial of Structured Treatment Interruption of HAART in HIV-Infected Adults in Abidjan (ANRS 1269 TRIVACAN)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: HIV
Structured treatment interruption
HAART
Sub-saharian africa
Treatment Interruption
Treatment Naive
Lead sponsor: French National Agency for Research on AIDS and Viral Hepatitis
Sponsor class: OTHER_GOV
Collaborators: name: Bristol-Myers Squibb
First posted: 2005-09-12
Enrollment: 840
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: To assess the non-inferiority at 24 months of two STI strategies of HAART compared with a continuous HAART in terms of :
measure: Percentage of patients with CD4 count over 350 per mm3
measure: Incidence of severe morbidity
measure: Incidence of mortality
Secondary outcomes:
measure: To compare at 24 months two STI strategies of HAART with a continuous HAART in terms of :
measure: HIV resistance to antiretroviral drugs
measure: Cost-utility
measure: Compliance to treatment
Other outcomes:
Locations:
city: Abidjan
country: Côte D'Ivoire
facility: Centre de Prise en Charge et de Formation ACONDA
city: Abidjan
country: Côte D'Ivoire
facility: Centre de Suivi des donneurs de sang, Centre National de Transfusion Sanguine
city: Abidjan
country: Côte D'Ivoire
facility: Centre Intégré de Recherches Biocliniques d'Abidjan
city: Abidjan
country: Côte D'Ivoire
facility: Service des Maladies Infectieuses et Tropicales, CHU de Treichville
city: Abidjan
country: Côte D'Ivoire
facility: Unité de Soins Ambulatoires et de Conseil, CHU de Treichville
Study officials:
affiliation: Unité INSERM 593, Université Victor Segalen Bordeaux 2
name: Xavier Anglaret, MD
role: STUDY_DIRECTOR
affiliation: Programme PACCI, Abidjan
name: Christine Danel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Unité INSERM 593, Université Victor Segalen Bordeaux 2
name: Roger Salamon, Pr
role: STUDY_CHAIR
affiliation: CHU Treichville
name: Emmanuel Bissagnene, Pr
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.