Structured Treatment Interruptions in Chronic HIV Infection

HIV Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00324103
• Other study ID #: ISS PART
• Status: Completed
• Phase: Phase 3
• First received: May 8, 2006
• Last updated: May 8, 2006
• Start date: June 2001
• Est. completion date: June 2004

Study information

• Verified date: October 2005
• Source: Istituto Superiore di Sanità
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Istituto Superiore di Sanità
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 600
• Est. completion date: June 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infection
• HIV Infections
• Infection

Intervention

Drug:
• Structured Treatment Interruptions

Locations

Country	Name	City	State
Italy	Istituto Superiore di Sanità	Rome

Sponsors (1)

Lead Sponsor	Collaborator
Istituto Superiore di Sanità

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	proportion of patients with CD4+ cell count above 500/mm3 at the end of follow-up (2 years) in the two treatment arms.
Secondary	occurrence of grade 3 or 4 adverse events (clinical and laboratory)
Secondary	proportion of patients with HIV-RNA < 400 copies/ml at the end of follow-up
Secondary	proportion of patients with CD4+ cell count > 350/mm3 at the end of follow-up
Secondary	rate of virological failure
Secondary	emergence of resistance
Secondary	HIV-related events.