Early and Intermittent Antiretroviral Therapy in Naive HIV Infected Adults

Study Overview
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Brief Summary
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The primary objective of the trial is to assess the ability of an early and intermittent antiretroviral therapy in maintaining an immunological stability in antiretroviral naive HIV infected adults, to offer a potential alternative strategy to differed and continuous antiretroviral treatment.This is a 2-year phase II, open-label, multicentric proof of concept trial. The patients included are treated following a pulse-therapy scheme, i.e. 6-month periods with once daily boosted-PI based therapy in alternance with 6-month periods without antiretroviral therapy. The preferentially recommended treatment of the study is atazanavir boosted with ritonavir, associated with a fixed combination of abacavir and lamivudine or emtricitabine + tenofovir.The patients are closely followed to assess the efficacy and the tolerance of the strategy, with clinical, biochemical, immunological, virological and pharmacokinetic evaluations.

Official Title
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ARNS 141 TIPI : A Pilot Trial to Assess the Ability of an Intermittent Antiretroviral Therapy in Maintaining an Immunological Stability in Antiretroviral naïve HIV Infected Adults, With CD4 Count Above 500/mm3

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Structured treatment interruption


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult confirmed HIV-1 infection no previous treatment with antiretroviral drugs or interleukin-2 CD4 count ≥ 500/mm3 no active opportunistic infection written informed consent Exclusion Criteria: non barrier contraception in women of child bearing potential, pregnant or breastfeeding woman, pregnancy project within the next 2 years HIV-2 infection (with or without HIV-1), recent HIV primary infection, resistance to trial drugs at study entry, Ag HBs+, HCV requiring specific therapy previous history of cerebrovascular accident or coronary heart disease, splenectomy previous CD4 count < 400/mm3 CD4 percentage < 15% hemoglobin < 8 g/dl, neutrophils < 750/mm3, platelets < 100.000/mm3, creatinine clearance < 50 ml/mn, AST or ALT or total bilirubin > 3 ULN

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intermittent treatment<br>6 months on antiretroviral treatment and 6 months off treatment | Drug: Structured treatment interruption<br>* The preferentially recommended treatment of the study is atazanavir boosted with ritonavir, associated with a fixed combination of abacavir and lamivudine or emtricitabine + tenofovir Usual dosage recommended : atazanavir : 300 mg/d ritonavir : 100 mg/d abacavir 600 mg and lamivudine 300 mg : once a day tenofovir 245 mg and emtricitabine 200 mg : once a day<br>* Other names: STI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients with mean CD4 count at M21 and M24 above or equal to the mean CD4 count at screening and inclusion, without experiencing a decrease below 400/mm3 throughout the study. |  | M21 and M24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients following the strategy of the trial and with AIDS related and non AIDS-related (cardiovascular, renal, hepatic, infectious, cancerous) serious clinical event |  | M12 and M24 | 
| number, type and time to AIDS and non AIDS-related serious clinical events |  | from week 0 to M24 | 
| number, type and time to clinical and biological events (whatever the grade of severity) |  | from week 0 to M24 | 
| existence and nature of HIV genotypic mutations associated with antiretroviral resistance |  | M9 and M24 and at any time visit in case of failure | 
| proportion of patients having followed the strategy of the trial |  | from week 0 to M24 | 
| evolution of HIV RNA and HIV DNA throughout the study |  | from week 0 to M24 for RNA and each 6 months for DNA | 
| Quality of life and observance (questionnaires) |  | QL each 6 months, observance at M1, M6, M13 and M18 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ANTIRETROVIRAL THERAPY, STRUCTURED TREATMENT INTERRUPTIONS, treatment naive