Anti-HIV Treatment Interruptions in HIV Infected Adults in South Africa

August 26, 2014 updated by: Luis Montaner, The Wistar Institute

A Randomized Clinical Trial Assessing Continuous HAART Versus Interrupted HAART in a Resource Poor Clinic

HIV infected people often must take anti-HIV drugs for long periods, leading to long-term drug exposure and toxicity. Interruptions in anti-HIV therapy, also known as structured treatment interruptions (STIs), may have few negative health effects and may be helpful to the overall long-term health of HIV-infected people. The purpose of this study is to determine if sequential short-term STIs of antiretroviral therapy (ART) in HIV infected individuals in a resource-constrained environment can retain the immune reconstitution benefits of continuous treatment while potentially lessening rates of toxicity associated with continuous therapy strategies and at the same time, lessen costs associated with ART.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Long-term toxicity and the high cost of medications are two problems faced by HIV infected people taking ART. Previous studies in HIV-infected patients suggest that ART with STIs may decrease drug exposure and lessen long-term drug toxicity, while not sacrificing viral suppression and patient health. This study will determine if ART with STIs can maintain the same level of immune function in HIV-infected people as continuous ART. This study will recruit patients in South Africa.

This study will last 3.5 years. At study entry, all participants will begin daily ART consisting of lamivudine, lopinavir/ritonavir, and stavudine. At Month 6, only participants who have responded well to ART (CD4 count greater than 450 cells/uL and viral load less than 50 copies/ml at Month 6) will be randomly assigned to one of two groups. Group 1 participants will participate in STIs during therapy, and Group 2 participants will receive continuous therapy. People in Group 1 will have treatment interruptions of 2, 4, and 8 weeks of duration in between 16-week periods of ART. Group 1 participants will re-initiate therapy if their CD4 count drops below 350 cells or evidence of clinical disease progression is present. Group 2 participants will continue taking ART throughout the study.

At screening, participants will undergo medical history assessment, a physical exam, and magnetic resonance imaging (MRI) and dual energy x-ray absorptiometry (DEXA) scans. There will be at least 22 study visits occurring approximately every 8 weeks, each lasting 45 to 60 minutes. At each study visit, participants will be required to bring any remaining pills with them so adherence can be assessed and will undergo medical assessments. Blood collection will occur at nearly all visits. For female participants, urine collection will occur at all visits. Participants will receive rabies vaccinations at Weeks 16, 17, and 22. A visit at Week 92 will include an MRI and participants will receive a rabies vaccine booster.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
      • Johannesburg, South Africa
        • University of the Witwatersrand

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • HIV infected
  • CD4 count of 200 to 350 cells/mm3 within 60 days of starting study treatment
  • Antiretroviral naive. Participants who have received antiretrovirals through postexposure prophylaxis or short course therapy to prevent mother-to-child transmission are eligible for this study.
  • Willing to adhere to study treatment
  • Willing to be followed for the duration of this study

Exclusion Criteria:

  • History of AIDS-defining illness (CDC category C). Patients with a history of pulmonary tuberculosis are not excluded.
  • Newly diagnosed AIDS-defining opportunistic infection or other condition requiring acute therapy at study entry
  • Previous therapy with agents with significant myelosuppressive, neurotoxic, pancreatotoxic, hepatotoxic, or cytotoxic potential within 30 days prior to study entry
  • History of immunomodulatory therapy within 4 weeks prior to screening, or cannot abstain from immunomodulators during the study
  • Previously received rabies vaccine
  • Current alcohol or drug abuse that, in the opinion of the investigator, may interfere with the study
  • Diarrhea (more than 6 stools per day for 7 consecutive days) within 30 days prior to study entry
  • Active or suspected acute hepatitis within 30 days of study entry
  • Bilateral peripheral neuropathy of Grade 2 or higher at screening
  • Inability to tolerate oral medication
  • Any clinical condition that, in the opinion of the investigator, would interfere with the study
  • Pregnancy or breastfeeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Highly active antiretroviral therapy (HAART) consisting of lamivudine, lopinavir/ritonovir, and stavudine for 16 weeks with three structured treatment interruptions for 2, 4, and 8 weeks each; rabies vaccine at Weeks 16, 17, 22 and 92.
Drug: Lamivudine
300 mg tablet taken orally daily
Behavioral: Structured treatment interruption
Interruptions in treatment will last 2, 4, and 8 weeks in between 16-week periods of ART
Other Names:
  • STI
Drug: Lopinavir/Ritonavir
400 mg lopinavir/100 mg ritonavir tablet taken orally twice daily
Drug: Stavudine
Dosage dependent on weight
Biological: Rabies de novo antigen
Vaccine injected intramuscularly
Active Comparator: 2
Continuous HAART consisting of lamivudine, lopinavir/ritonovir, and stavudine throughout the study; rabies vaccine at Weeks 16, 17, 22 and 92.
Drug: Lamivudine
300 mg tablet taken orally daily
Drug: Lopinavir/Ritonavir
400 mg lopinavir/100 mg ritonavir tablet taken orally twice daily
Drug: Stavudine
Dosage dependent on weight
Biological: Rabies de novo antigen
Vaccine injected intramuscularly

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To compare intermittent ART to continuous therapy by comparing endpoint CD4 counts between Groups 1 and 2
Time Frame: Throughout study
Throughout study
Response to rabies vaccination and booster
Time Frame: Weeks 16, 22, and 92
Weeks 16, 22, and 92

Secondary Outcome Measures

Outcome Measure
Time Frame
Comparison of treatment-associated toxicity and safety of 2 to 8 weeks of antiretroviral therapy (ART) interruption versus continuous ART
Time Frame: Throughout study
Throughout study
Determine the outcome of immune reconstitution by monitoring changes in T-cell subsets and the ability to maintain cell-mediated responses against various antigens
Time Frame: Before and after intermittent strategy
Before and after intermittent strategy
Viral evolution and genotypic changes that confer drug resistance
Time Frame: During intermittent and continuous treatment
During intermittent and continuous treatment
Effect of treatment interruption on cardiovascular adverse experiences risk factors
Time Frame: From Weeks 0 to 144
From Weeks 0 to 144

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Wistar Institute

Investigators

  • Principal Investigator: Luis J. Montaner, DVM, MSc, DPhil, The Wistar Institute
  • Principal Investigator: Ian M. Sanne, MBBCH, FCP(SA), DTM&H, University of Witwatersrand, South Africa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

March 1, 2010

Study Completion (Actual)

March 1, 2010

Study Registration Dates

First Submitted

January 4, 2005

First Submitted That Met QC Criteria

January 4, 2005

First Posted (Estimate)

January 5, 2005

Study Record Updates

Last Update Posted (Estimate)

August 27, 2014

Last Update Submitted That Met QC Criteria

August 26, 2014

Last Verified

November 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1R01AI051986-01A2 (U.S. NIH Grant/Contract)
  • R01AI051986 (U.S. NIH Grant/Contract)
  • Protocol 2411209
  • R01 A151986-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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