Tuberculosis Prevention for HIV Infected Adults

Novel TB Prevention Regimens for HIV-Infected Adults

This study compares three different tuberculosis (TB) prevention regimens against the standard regimen of 6 months of isoniazid. It is being conducted in Soweto, South Africa. People who are HIV positive and have a positive tuberculin skin test without signs of active tuberculosis may join.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Tuberculosis
• Intervention / Treatment: Drug: Isoniazid; Drug: Rifapentine; Drug: Rifampin

Detailed Description

AIDS is the leading cause of death in sub-Saharan Africa, and TB is the leading cause of death in patients with AIDS on that continent. Preventive therapy for HIV infected people with latent TB infection is important to reduce the risk of progression to active TB. Although preventive TB therapy is generally recommended throughout the Western world for people with HIV, it is not routinely advocated or provided to patients in developing countries. Six months of self-supervised INH is the gold standard of preventive TB therapy. Newer preventive regimens with a shorter duration of treatment and intermittent dosing could improve compliance and permit treatment supervision through dosing observation. This study will compare the standard INH regimen with two new regimens: rifapentine and INH observed once weekly for 12 weeks and rifampin and INH observed twice weekly for 12 weeks.

Patients will be interviewed to identify risk factors for TB and symptoms of active TB. A physical examination and chest radiograph will be performed on all potential patients to identify and exclude all active TB cases (these patients will be referred for appropriate treatment of their infection).

Patients who meet the inclusion criteria will be randomized to one of the following treatment arms: rifapentine/INH for 12 weeks, observed weekly; rifampin/INH for 12 weeks, observed twice weekly; INH for 6 months, self-supervised; or continuous INH, self-supervised. Patients randomized to the two self-administered INH arms will be given a 1 month supply of INH and instructed to take one pill each day. Patients in the continuous INH arm will take INH continuously until the end of the study. Depending on when the patient enrolls in the study, the patient could take INH for 1 to 4 years. Each patient will be provided with education on the need to adhere to the protocol and information on potential study drug related toxicity. All patients will be given their first dose of study medication during the enrollment period. Patients in the shorter-course, observed regimens will be given each of their doses in a clinic under the supervision of a study nurse.

At each study encounter, possible toxicity will be assessed via interview. Patients will be followed every 6 months after the completion of preventive therapy until the study closes. Outreach workers will perform home visits to encourage follow-up and determine vital status for any patient who has missed a scheduled follow-up visit. Patients with evidence of active tuberculosis at any follow-up visit will be evaluated and treated appropriately. Patients will be offered a small incentive for fulfilling study requirements. The equivalent of $5 (30 rand) will be paid after successful entry into the trial and at each 6 month visit as compensation for time spent in the study and to cover travel expenses.

• Study Type: Interventional
• Enrollment (Actual): 1148
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Africa
  • Soweto, South Africa
    • Chris Hani Baragwanath Hospital

Participation Criteria

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
• Tuberculin test (PPD) positive 5 mm or greater
• Chest x-ray negative for pulmonary tuberculosis

Exclusion Criteria:

• Pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 2	Drug: Isoniazid; 300mg; Drug: Rifampin; Rifampin 600 mg
Active Comparator: 1	Drug: Isoniazid; 300mg; Drug: Rifapentine; Rifapentine 900 mg
Active Comparator: 3	Drug: Isoniazid; 300mg
Active Comparator: 4	Drug: Isoniazid; 300mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Development of confirmed, probable, or possible active pulmonary or extrapulmonary tuberculosis (TB)	6/2008

Secondary Outcome Measures

Outcome Measure	Time Frame
Risk of TB and death	6/2008
rates of adherence, adverse reactions and treatment discontinuation	6/2008
patterns of antibiotic resistance	6/2008
clinical and epidemiological factors associated with developing TB	6/2008

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Richard Chaisson, MD, Johns Hopkins Medical Institute

Publications and helpful links

General Publications

• Singh P, Moulton LH, Barnes GL, Gupta A, Msandiwa R, Chaisson RE, Martinson NA. Pregnancy in Women With HIV in a Tuberculosis Preventive Therapy Trial. J Acquir Immune Defic Syndr. 2022 Dec 1;91(4):397-402. doi: 10.1097/QAI.0000000000003078.
• Martinson NA, Barnes GL, Moulton LH, Msandiwa R, Hausler H, Ram M, McIntyre JA, Gray GE, Chaisson RE. New regimens to prevent tuberculosis in adults with HIV infection. N Engl J Med. 2011 Jul 7;365(1):11-20. doi: 10.1056/NEJMoa1005136.

Study record dates

Study Major Dates

• Study Start: September 1, 2002
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: March 27, 2003
• First Submitted That Met QC Criteria: March 27, 2003
• First Posted (Estimate): March 28, 2003

Study Record Updates

• Last Update Posted (Estimate): October 22, 2012
• Last Update Submitted That Met QC Criteria: October 19, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Preventive therapy
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Fatty Acid Synthesis Inhibitors; Rifapentine; Rifampin; Isoniazid
• Other Study ID Numbers: 1R01AI048526-01A1 (U.S. NIH Grant/Contract); 5R01AI048526-02 (U.S. NIH Grant/Contract)