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Effectiveness of Anti-HIV Therapy (HAART) in HIV-Infected Patients With Tuberculosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00004736
Recruitment Status : Completed
First Posted : August 31, 2001
Last Update Posted : September 11, 2008
Information provided by:

Study Description
Brief Summary:

The purpose of this study is to see if a type of anti-HIV therapy called HAART is effective in lowering levels of HIV and boosting the immune system in HIV-infected patients with tuberculosis (TB).

HIV-infected patients with TB have higher levels of HIV and lower CD4 cell counts (cells in the body that fight infection) than HIV-infected patients without TB. HAART has been effective in reducing HIV levels and increasing CD4 cells in patients without TB. However, its effects in HIV-infected patients with TB are unknown.

Condition or disease Intervention/treatment Phase
HIV Infections Tuberculosis Drug: Nelfinavir mesylate Drug: Ethambutol hydrochloride Drug: Isoniazid Drug: Pyrazinamide Drug: Lamivudine Drug: Rifabutin Drug: Stavudine Drug: Zidovudine Phase 1

Detailed Description:

Previous studies have focused on characterizing viral and immune dynamics after initiation of HAART in patients without opportunistic infection. The development of TB in HIV-infected individuals is associated with an elevation in HIV RNA levels, a decrease in CD4 cell counts, and an increase in activated (CD38) lymphocytes and proinflammatory cytokines (IL-1, TNF-alpha, and IL-6). Response to HAART may differ in individuals with an active opportunistic infection such as TB.

HIV-infected patients with active TB follow an anti-TB regimen including rifabutin and are observed for a maximum of 24 weeks before they initiate HAART. Plasma samples for 24-hour post-rifabutin dosing are collected at entry and at Weeks 4, 8, and 12, then again at Weeks 2, 3, 4, 12, and 24 after HAART initiation. Analyses of these samples are used to explore the relationship between cytokines and rifabutin metabolism and the effect of nelfinavir on rifabutin pharmacokinetics. The HAART regimen is nelfinavir plus lamivudine (3TC) plus either zidovudine (ZDV) or stavudine (d4T). After initiation of HAART, all patients undergo intensive monitoring of viral and immune dynamics for 2 months. The patients continue to be followed for 1 year from the time of starting HAART. Neither the HAART drug regimen nor anti-TB medications will be provided by the study and must be obtained by prescription. If patients are intolerant of the HAART regimen or exhibit virologic rebound, primary providers can alter or modify this regimen. As part of substudy A5065s, patients who experience signs or symptoms of paradoxical reactions (i.e., new persistent fevers that develop after initiating HAART and which last for more than 1 week without an identifiable source; marked worsening or emergence of intrathoracic lymphadenopathy, pulmonary infiltrates; worsening or emergence of cervical adenopathy on serial physical examinations; or worsening of other tuberculous lesions) have additional clinical evaluations (including a chest x-ray, a target clinical assessment, concomitant medications, and signs and symptoms) weekly for 4 weeks, then every month thereafter until the symptoms resolve.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Primary Purpose: Treatment
Official Title: Viral and Immune Dynamics in HIV-Infected Patients With Tuberculosis

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U.S. FDA Resources

Arms and Interventions

Outcome Measures

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

Patients may be eligible for this study if they:

  • Are HIV-positive.
  • Have an HIV RNA level of 20,000 copies/ml or more within 30 days of study entry.
  • Are at least 18 years old.
  • Agree to use an effective method of birth control during the study.
  • Agree to be treated with rifabutin at least 2 weeks before starting HAART (applies only to patients infected with TB).
  • Plan to start HAART within 6 months of starting TB therapy (applies only to patients infected with TB).
  • Can take 3TC, nelfinavir, and either ZDV or d4T.
  • Are available for follow-up for at least 1 year.

Exclusion Criteria

Patients will not be eligible for this study if they:

  • Have taken a combination of anti-HIV drugs for greater than 3 months.
  • Have started HAART since they were infected with TB (applies only to patients infected with TB).
  • Are resistant to more than one medication used to treat TB (applies only to patients infected with TB).
  • Have had more than 16 weeks of TB therapy (applies only to patients infected with TB).
  • Are taking rifampin to treat TB and cannot switch to rifabutin at least 2 weeks before starting HAART (applies only to patients infected with TB).
  • Are pregnant or breast-feeding.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00004736

United States, California
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
United States, Illinois
Cook County Hosp
Chicago, Illinois, United States, 60612
United States, New York
Beth Israel Med Ctr
New York, New York, United States, 10003
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Columbia Presbyterian Med Ctr
New York, New York, United States, 10032
United States, Pennsylvania
Univ of Pennsylvania at Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
Brown Univ / Miriam Hosp
Providence, Rhode Island, United States, 02906
Miriam Hosp / Brown Univ
Providence, Rhode Island, United States, 02906
United States, Tennessee
Vanderbilt Univ Med Ctr
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: Diane Havlir
Study Chair: Constance Benson
More Information

ClinicalTrials.gov Identifier: NCT00004736     History of Changes
Other Study ID Numbers: ACTG A5062
First Posted: August 31, 2001    Key Record Dates
Last Update Posted: September 11, 2008
Last Verified: June 2003

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
AIDS-Related Opportunistic Infections
Drug Therapy, Combination
Antitubercular Agents
Anti-HIV Agents

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
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents