Antiretroviral Treatment With Structured Treatment Interruptions (STI) Versus Continuous Antiretroviral Treatment in HIV+ Patients With Persistent Suppression of Viral Replication
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Istituto Superiore di Sanità
- Enrollment
- 600
- Locations
- 2
- Primary Endpoint
- proportion of patients with CD4+ cell count above 500/mm3 at the end of follow-up (2 years) in the two treatment arms.
Study Overview
Brief Summary
In the last years Structured Treatment Interruptions (STI) have been proposed to reduce HAART-related toxicity and to increase patients' compliance. ISS PART is a randomized comparison of repeated STIs versus continuous HAART in chronically HIV-infected subjects with persistent suppression of viral replication. The two arms of the study will be compared in terms of immunological response (proportion of patients with CD4>500/mmc) at 2 years.
Detailed Description
Patients are randomized in a 1 to 1 ratio to continue their current antiretroviral regimen (Arm A) or to undergo structured treatment interruptions (STI) (Arm B) according to the following scheme: STIs of 1, 1, 2, 2 and 3 months each followed by a 3-month therapy period.
During STIs, therapy is resumed in the presence of an HIV-RNA rebound > 50,000 copies/ml or of a CD4+ T cell decline > 25% of the baseline count (> 35% for patients with CD4+ > 500/mm3 at randomization). After the first cycle, subsequent STIs are performed only if an HIV-RNA level < 400 copies/ml is reached after 2 months of therapy resumption.
At the time of treatment interruptions patients in arm B who are on treatment with non-nucleoside reverse transcriptase inhibitors suspend these drugs first and continue the treatment with the other drugs of the combination for 3 days if nevirapine-treated and for 6 days in case of previous efavirenz-based regimen.
Patients are seen at the clinical site every three months for arm A and monthly for arm B. On these occasions, blood samples are obtained for biochemical and viro-immunological assessments.
The toxicity grading scale of the AIDS Clinical Trial Group (ACTG) is used for the reporting of clinical and laboratory adverse events.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •first-line antiretroviral therapy (3 or 4 drugs) for 6 to 18 months (one previous therapy change for toxicity or non-compliance is allowed)
- •HIV-RNA level below 400 copies/ml for at least 6 months;
- •CD4+ count > 350 /mm3;
- •pre-HAART CD4+ > 100/mm3
- •no previous AIDS diagnosis.
Exclusion Criteria
- •Previous antiretroviral therapy with 1 or 2 drugs (except ARV prophylaxis in pregnancy)
- •Pregnancy or breastfeeding
- •Previous diagnosis of AIDS
- •Grade 3 or 4 adverse event in the 15 days before enrolment
- •Neoplasia
- •Previous therapy with IL-2, interferon (in the last 2 years) or experimental therapies
Outcomes
Primary Outcomes
proportion of patients with CD4+ cell count above 500/mm3 at the end of follow-up (2 years) in the two treatment arms.
Secondary Outcomes
- occurrence of grade 3 or 4 adverse events (clinical and laboratory)
- proportion of patients with HIV-RNA < 400 copies/ml at the end of follow-up
- proportion of patients with CD4+ cell count > 350/mm3 at the end of follow-up
- rate of virological failure
- emergence of resistance
- HIV-related events.