Clinical trial NCT00324103: Structured Treatment Interruptions in Chronic HIV Infection
Official title: Antiretroviral Treatment With Structured Treatment Interruptions (STI) Versus Continuous Antiretroviral Treatment in HIV+ Patients With Persistent Suppression of Viral Replication
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infection
Keywords: HIV
Chronic Infection
Clinical Trial
Structured Treatment Interruption
Lead sponsor: Istituto Superiore di Sanità
Sponsor class: OTHER
First posted: 2006-05-10
Enrollment: 600
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: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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:
measure: occurrence of grade 3 or 4 adverse events (clinical and laboratory)
measure: proportion of patients with HIV-RNA < 400 copies/ml at the end of follow-up
measure: proportion of patients with CD4+ cell count > 350/mm3 at the end of follow-up
measure: rate of virological failure
measure: emergence of resistance
measure: HIV-related events.
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Istituto Superiore di Sanità
Study officials:
affiliation: Istituto Superiore di Sanità
name: Stefano Vella, MD
role: STUDY_CHAIR
References: