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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00158405
• Other study ID #: ANRS 1269 TRIVACAN
• Status: Completed
• Phase: Phase 3
• First received: September 7, 2005
• Last updated: December 29, 2008
• Start date: December 2002
• Est. completion date: December 2006

Study information

• Verified date: December 2008
• Source: French National Agency for Research on AIDS and Viral Hepatitis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Cote d'Ivoire: Ministry of AIDS
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 840
• Est. completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Procedure:
• Structured Treatment Interruption

Drug:
• Zidovudine (ZDV)

• Lamivudine (3TC)

• Efavirenz (EFV)

• Ritonavir (NRV)

• Indinavir (IDV)

Locations

Country	Name	City	State
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	Abidjan

Sponsors (2)

Lead Sponsor	Collaborator
French National Agency for Research on AIDS and Viral Hepatitis	Bristol-Myers Squibb

Country where clinical trial is conducted

Côte D'Ivoire, 

References & Publications (3)

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 — View Citation

Danel C, Moh R, Minga A, Anzian A, Ba-Gomis O, Kanga C, Nzunetu G, Gabillard D, Rouet F, Sorho S, Chaix ML, Eholié S, Menan H, Sauvageot D, Bissagnene E, Salamon R, Anglaret X; Trivacan ANRS 1269 trial group. CD4-guided structured antiretroviral treatment — View 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 Côte d'Ivoire. Antivir Ther. 2005;10(5):615-24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the non-inferiority at 24 months of two STI strategies of HAART compared with a continuous HAART in terms of :
Primary	Percentage of patients with CD4 count over 350 per mm3
Primary	Incidence of severe morbidity
Primary	Incidence of mortality
Secondary	To compare at 24 months two STI strategies of HAART with a continuous HAART in terms of :
Secondary	HIV resistance to antiretroviral drugs
Secondary	Cost-utility
Secondary	Compliance to treatment