Structured Treatment Interruptions in Chronic HIV Infection

Sponsor

Istituto Superiore di Sanità (Other)

Overall Status

Completed

CT.gov ID

NCT00324103

Collaborator

(none)

600

Enrollment

Location

Duration (Months)

16.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infection	Drug: Structured Treatment Interruptions	Phase 3

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.

In arm B, plasma genotype is obtained in samples taken after 15 or 30 days of drug suspension.

Patients will discontinue the study in case of : early therapy resumption for 2 consecutive times (only arm B patients); acute retroviral syndrome (only for arm B patients); AIDS-defining event; severe adverse event; pregnancy; non-compliance; patient' s request; physician's decision.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Antiretroviral Treatment With Structured Treatment Interruptions (STI) Versus Continuous Antiretroviral Treatment in HIV+ Patients With Persistent Suppression of Viral Replication

Study Start Date :

Jun 1, 2001

Study Completion Date :

Jun 1, 2004

Outcome Measures

Primary Outcome Measures

proportion of patients with CD4+ cell count above 500/mm3 at the end of follow-up (2 years) in the two treatment arms. []

Secondary Outcome Measures

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. []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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