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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Luis Montaner, The Wistar Institute
ClinicalTrials.gov Identifier:
NCT00100646
First received: January 4, 2005
Last updated: August 26, 2014
Last verified: November 2013
  Purpose

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.


Condition Intervention
HIV Infections
Behavioral: Structured treatment interruption
Drug: Lamivudine
Drug: Lopinavir/Ritonavir
Drug: Stavudine
Biological: Rabies de novo antigen

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Clinical Trial Assessing Continuous HAART Versus Interrupted HAART in a Resource Poor Clinic

Resource links provided by NLM:


Further study details as provided by The Wistar Institute:

Primary Outcome Measures:
  • To compare intermittent ART to continuous therapy by comparing endpoint CD4 counts between Groups 1 and 2 [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Response to rabies vaccination and booster [ Time Frame: Weeks 16, 22, and 92 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Comparison of treatment-associated toxicity and safety of 2 to 8 weeks of antiretroviral therapy (ART) interruption versus continuous ART [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Viral evolution and genotypic changes that confer drug resistance [ Time Frame: During intermittent and continuous treatment ] [ Designated as safety issue: Yes ]
  • Effect of treatment interruption on cardiovascular adverse experiences risk factors [ Time Frame: From Weeks 0 to 144 ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: March 2007
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Behavioral: Structured treatment interruption
Interruptions in treatment will last 2, 4, and 8 weeks in between 16-week periods of ART
Other Name: STI
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
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00100646

Locations
South Africa
University of the Witwatersrand
Johannesburg, South Africa
Sponsors and Collaborators
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 the Witwatersrand
  More Information

Additional Information:
Publications:

Responsible Party: Luis Montaner, Professor and Director, HIV-1 Immunopathogenesis Laboratory, The Wistar Institute
ClinicalTrials.gov Identifier: NCT00100646     History of Changes
Other Study ID Numbers: 1R01AI051986-01A2, R01 AI 51986, Protocol 2411209, 1 R01 AI051986-01A2, R01 A151986-01
Study First Received: January 4, 2005
Last Updated: August 26, 2014
Health Authority: United States: Federal Government

Keywords provided by The Wistar Institute:
Treatment Interruption
Treatment Naive

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Ritonavir
Lopinavir
Lamivudine
Stavudine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Antimetabolites

ClinicalTrials.gov processed this record on September 18, 2014