Immune and Viral Outcomes of HIV-1 Therapy Interruption

Study Description

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Brief 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.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Behavioral: Treatment interruption/reinitiation schedule	Phase 1

Detailed 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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	20 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Immune and Viral Outcomes of HIV-1 Therapy Interruption
Study Start Date :	September 2000
Actual Primary Completion Date :	May 2003
Actual Study Completion Date :	July 2003

Arms and Interventions

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Outcome Measures

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Primary Outcome Measures :

1. Viral suppression in the absence of therapy, compared to a structured treatment interruption (STI) group maintaining continual suppression

Secondary Outcome Measures :

1. Safety of sequential STIs
2. 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
3. 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

Eligibility Criteria

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Ages Eligible for Study:	17 Years and older (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

United States, Pennsylvania
The Wistar Institute
Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

The Wistar Institute

Investigators

Principal Investigator:	Luis J. Montaner	The Wistar Institute

More Information

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Publications of Results:

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. Epub 2004 Dec 28.

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. 2003 Nov 7;17(16):2337-43.

Other Publications:

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

Responsible Party:	Luis Montaner, Professor and Director, HIV-1 Immunopathogenesis Laboratory, The Wistar Institute
ClinicalTrials.gov Identifier:	NCT00051818 History of Changes
Other Study ID Numbers:	5R01AI048398-01 ( U.S. NIH Grant/Contract ); AI048398
First Posted:	January 24, 2003
Last Update Posted:	February 9, 2016
Last Verified:	December 2005

Keywords provided by Luis Montaner, The Wistar Institute:

chronic HIV infection; treatment interruption; HIV-specific immune response	immune response; virological response; treatment experienced

Additional relevant MeSH terms:

HIV Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases	Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases