Staccato: A Trial of CD4 Guided Treatment Interruption, Compared to Continuous Treatment, for HIV Infection

Study Overview
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Brief Summary
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Treatment of HIV repairs the immune system, but continuous treatment is expensive and causes side effects. Would it not be better to treat intermittently, e.g. stop treatment when the immune system has recovered, and start again only when damage reappears? That is the question which STACCATO proposes to answer. Approximately 500 patients were recruited for this trial from 2002 to 2004. One third were treated continuously; in two thirds, the treatment was interrupted whenever the CD4 count, a measure of immune recovery, exceeded 350. At the end of 2005, the two treatment groups will be compared in order to see which fared better regarding amount of drugs used, side effects, CD4 counts, and development of resistance to treatment.

Detailed Description
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Continuous treatment has been very successful in diminishing the diseases and deaths caused by HIV. However, continuous treatment is expensive. Intermittent treatment will always cost less than continuous treatment, and therefore has the potential to facilitate access to highly active antiretroviral therapy (HAART) in developing countries. HAART also causes many undesirable effects. Intermittent treatment decreases exposure to drugs and is therefore expected to decrease side effects. STACCATO is a randomised trial of intermittent versus continuous anti-retroviral treatment. At least 600 patients on HAART, with viremia below 50 copies/ml and CD4 count above 350 cells/ml were randomised to one of two arms, in 1:2 proportions: Arm 1: Continuation (control) arm: Drugs are continued or changed according to current guidelines and good clinical practice. Arm 2: CD4-guided arm: Drugs discontinued and reintroduced according to CD4 counts, with HAART being administered only if CD4 count is < 350 cells/ml. Randomized treatment will continue during an average of approximately 2 years, and will be followed by a period of 12 to 24 weeks' continuous treatment, for patients in both arms. Endpoints: The amount of drugs used, side effects, viremia and CD4 counts, number of clinical events, at the end of the randomized treatment period, and again 12 to 24 weeks later. A subproject will study the effect of treatment interruption on resistance development, mutations in proviral DNA and proviral DNA levels.

Official Title
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A Randomized Trial of CD4 Guided Treatment Interruption, Compared to Continuous Treatment, for HIV Infection

Conditions
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HIV Infection, AIDS

Intervention / Treatment
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* Drug: Treatment interruption


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CD4 lymphocyte count above 350/microliter and viral HIV1-RNA below 50 copies/ml on antiretroviral treatment. Exclusion Criteria: Virologic failure of treatment. Failure of treatment defined as a treatment switch motivated by high viral loads on treatment.

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 |
| --- |
|Drug: Treatment interruption|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amounts of drugs used |  |  | 
| Response of viral load to retreatment after interruption |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opportunistic infections and deaths |  |  | 
| Adverse effects |  |  | 
| CD4 counts |  |  | 
| Resistance development |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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STI, Scheduled treatment interruptions