Clinical trial NCT00122551: Intermittent Therapy in HIV-1 Infected Patients With Successful Viral Suppression Under Highly Active Antiretroviral Therapy (HAART)
Official title: A Prospective, Randomized, Multicenter Trial of Intermittent Therapy in HIV-Infected Patients With Successful Viral Suppression Under HAART (ANRS 106 Window Trial)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: HIV Infections
Keywords: HIV infections
Lead sponsor: French National Agency for Research on AIDS and Viral Hepatitis
Sponsor class: OTHER_GOV
First posted: 2005-07-22
Enrollment: 400
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: Although lifelong continuous therapy with HAART remains the standard of care of HIV infection, allowing to achieve undetectable plasma viral RNA, restore CD4 cell count and provide substantial decline in HIV-related morbidity and mortality, long-term toxicity associated with antiretroviral therapy is a real concern. The purpose of this study is to compare an intermittent therapy strategy to a continuous treatment in patients with chronic and well controlled HIV-1 infection.

Detailed description: Although lifelong continuous therapy with HAART remains the standard of care of HIV infection, allowing to achieve undetectable plasma viral RNA, restore CD4 cell count and provide substantial decline in HIV-related morbidity and mortality, long-term toxicity associated with antiretroviral therapy is a real concern.

The purpose of this study is to compare an intermittent therapy (IT) strategy (8 weeks off / 8 weeks on) to a continuous treatment (CT) in patients with chronic and well controlled HIV-1 infection (CD4 over 450/µl and plasma HIV1-RNA below 200 cp/ml) under HAART, over a 96-week study period.

The study hypothesis is that intermittent therapy is not inferior to continuous therapy in maintaining a CD4 cell above 300/µl. It will compare the proportions of and time to immunological failure (CD4 count below 300/µl confirmed by a retest 14 days later) in the IT and CT groups.

Eligibility criteria: Inclusion Criteria:

* HIV-1 infection
* CD4 cell count over 450/µl for at least 6 months prior to screening
* Plasma HIV1-RNA below 200 cop/ml for at least 6 months prior to screening
* Stable and well tolerated ART for at least 6 months prior to screening
* Acceptable methods of contraception
* Patient able to comply with the protocol
* Informed consent signed prior to (or at) screening

Exclusion Criteria:

* CD4 nadir below 100/µl
* Abacavir or nevirapine in the current ART
* Hepatitis B with 3-TC, adefovir or tenofovir current therapy
* Current or upcoming treatment with interferon for hepatitis B or C
* History of AIDS-defining event in the 18 months prior to screening
* Pregnancy or breast feeding

Primary outcomes:
measure: Immunological failure, defined by a CD4 cell count below 300/µl confirmed by a retest 14 days later during the study
Secondary outcomes:
measure: 1993 Centers for Disease Control (CDC) classification of HIV infection B or C events
measure: Proportions of patients with CD4 count over 450/µl at week 96
measure: Proportions of patients with plasma HIV load over 400 and 1000/ml thresholds
measure: Plasma and peripheral blood mononuclear cells (PBMC) HIV resistance patterns
measure: Proportions of patients withdrawing initial treatment strategy
measure: Assessment of lipodystrophy and metabolic abnormalities
measure: Antiretroviral therapy (ARTs) adherence assessment
measure: Quality of life assessment
measure: Cost impact of the strategies
Other outcomes:
Locations:
city: Paris
country: France
facility: Service des Maladies Infectieuses
city: Toulouse Cedex 9
country: France
facility: Service des Maladies Infectieuses et Tropicales Hopital Purpan
Study officials:
affiliation: Service des Maladies Infectieuses et Tropicales Hopital Purpan Toulouse
name: Bruno Marchou, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Inserm SC10
name: Jean Pierre Aboulker, MD
role: STUDY_CHAIR
References:
citation: Delobel P, Saliou A, Nicot F, Dubois M, Trancart S, Tangre P, Aboulker JP, Taburet AM, Molina JM, Massip P, Marchou B, Izopet J; ANRS 106-Window Study Team. Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. PLoS One. 2011;6(6):e21655. doi: 10.1371/journal.pone.0021655. Epub 2011 Jun 27.
citation: Charreau I, Jeanblanc G, Tangre P, Boyer L, Saouzanet M, Marchou B, Molina JM, Aboulker JP, Durand-Zaleski I; ANRS 106 Study Group. Costs of intermittent versus continuous antiretroviral therapy in patients with controlled HIV infection: a substudy of the ANRS 106 Window Trial. J Acquir Immune Defic Syndr. 2008 Dec 1;49(4):416-21. doi: 10.1097/QAI.0b013e31818a657c.