Immune and Viral Outcomes of HIV-1 Therapy Interruption

HIV Infections Clinical Trial

Official title:

Immune and Viral Outcomes of HIV-1 Therapy Interruption

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00051818
• Other study ID #: 5R01AI48398-01
• Secondary ID: AI048398
• Status: Completed
• Phase: Phase 1
• First received: January 16, 2003
• Last updated: February 8, 2016
• Start date: September 2000
• Est. completion date: July 2003

Study information

• Verified date: December 2005
• Source: The Wistar Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if stopping anti-HIV drugs for a period of time is safe and effective for enhancing the immune function of patients with HIV.

Description:

Our preliminary studies have shown that structured treatment interruption of highly active antiretroviral therapy (HAART) may boost patients' immune responses to HIV-1. In this study, we will test the hypothesis that repeated structured treatment interruptions will increase HIV-1 immunity and result in better control of viral replication than in controls. We will test this hypothesis by determining time to viral rebound after withdrawal of antiretroviral therapy in a randomized, non-blinded study of a well-characterized subject population from a single center. Patients in this study will be randomized to either treatment interruption or control groups. Patients will be monitored for adherence to therapy and changes in immune status following HAART interruption. CD4 percentage, CD 4 and CD8 mediated anti-HIV-1 responses, cell surface T-cell antigen expression, and thymic function will be assessed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: July 2003
• Est. primary completion date: May 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 17 Years and older

Eligibility

Inclusion Criteria

• HIV-1 positive

• HIV RNA < 500 copies/ml on a regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) and either one protease inhibitor (PI) or one nonnucleoside reverse transcriptase inhibitor (NNRTI) for 6 months prior to study entry - HIV RNA < 50 copies/ml at study screening

• CD4 > 400 cells/mm3 with CD4 nadir of > 100 cells/mm3

• Agree to Medication Event Monitoring System monitoring of one component of antiretroviral regimen

• HIV-1 viral load >10,000 copies/ml at any time prior to initiating the current uninterrupted HAART regimen

• Willing to abstain from all immunomodulatory drugs during the study

Study Design

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Behavioral:
• Treatment interruption/reinitiation schedule

Locations

Country	Name	City	State
United States	The Wistar Institute	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
The Wistar Institute

Country where clinical trial is conducted

United States, 

References & Publications (3)

Montaner LJ. Structured treatment interruptions to control HIV-1 and limit drug exposure. Trends Immunol. 2001 Feb;22(2):92-6. Review. — View Citation

Papasavvas E, Grant RM, Sun J, Mackiewicz A, Pistilli M, Gallo C, Kostman JR, Mounzer K, Shull J, Montaner LJ. Lack of persistent drug-resistant mutations evaluated within and between treatment interruptions in chronically HIV-1-infected patients. AIDS. 2 — View Citation

Papasavvas E, Kostman JR, Mounzer K, Grant RM, Gross R, Gallo C, Azzoni L, Foulkes A, Thiel B, Pistilli M, Mackiewicz A, Shull J, Montaner LJ. Randomized, controlled trial of therapy interruption in chronic HIV-1 infection. PLoS Med. 2004 Dec;1(3):e64. Ep — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Viral suppression in the absence of therapy, compared to a structured treatment interruption (STI) group maintaining continual suppression
Secondary	Safety of sequential STIs
Secondary	changes in immune reconstitution in relation to sequential STIs, including CD4 T-cell changes, recall responses, and T-cell activation, as measured by cell surface antigen changes
Secondary	genotypic changes occurring in HIV-1 protease and reverse transcriptase regions after sequential STIs and their relation to clinical failure under the ART regimen at study entry