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

Study Overview
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Brief Summary
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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
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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 : 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. 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.

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* Procedure: Structured Treatment Interruption
* Drug: Zidovudine (ZDV)
* Drug: Lamivudine (3TC)
* Drug: Efavirenz (EFV)
* Drug: Ritonavir (NRV)
* Drug: Indinavir (IDV)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Structured Treatment Interruption|nan|
|Drug: Zidovudine (ZDV)|nan|
|Drug: Lamivudine (3TC)|nan|
|Drug: Efavirenz (EFV)|nan|
|Drug: Ritonavir (NRV)|nan|
|Drug: Indinavir (IDV)|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Structured treatment interruption, HAART, Sub-saharian africa, Treatment Interruption, Treatment Naive