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

HIV Infections Clinical Trial

Official title:

Viral and Immune Dynamics in HIV-Infected Patients With Tuberculosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004736
• Other study ID #: ACTG A5062
• Secondary ID: AACTG A5062
• Status: Completed
• Phase: Phase 1
• First received: February 25, 2000
• Last updated: September 10, 2008

Study information

• Verified date: June 2003
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Efficacy Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• Tuberculosis

Intervention

Drug:
• Nelfinavir mesylate

• Ethambutol hydrochloride

• Isoniazid

• Pyrazinamide

• Lamivudine

• Rifabutin

• Stavudine

• Zidovudine

Locations

Country	Name	City	State
United States	Cook County Hosp	Chicago	Illinois
United States	Univ of Southern California / LA County USC Med Ctr	Los Angeles	California
United States	Vanderbilt Univ Med Ctr	Nashville	Tennessee
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Beth Israel Med Ctr	New York	New York
United States	Columbia Presbyterian Med Ctr	New York	New York
United States	Univ of Pennsylvania at Philadelphia	Philadelphia	Pennsylvania
United States	Brown Univ / Miriam Hosp	Providence	Rhode Island
United States	Miriam Hosp / Brown Univ	Providence	Rhode Island
United States	Univ of California / San Diego Treatment Ctr	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

External Links

•   Click here for more information about Isoniazid
•   Click here for more information about Lamivudine
•   Click here for more information about Nelfinavir mesylate
•   Click here for more information about Rifabutin
•   Click here for more information about Stavudine
•   Click here for more information about Zidovudine
•   Haga clic aquí para ver información sobre este ensayo clínico en español.