Prevention of Early Mortality by Presumptive Tuberculosis (TB) Treatment

• Status: Terminated
• Trial end date: 2013-06-01
• Target enrollment: 0
• Participant gender: All

Summary

This study investigates the prevention of early mortality in patients initiating antiretroviral therapy (ART) in sub-Saharan Africa where 79% of the co-infected cases of TB reside. Many published studies have shown a surprisingly high proportion of all patients initiated on ART dying within 6 months (8-26%) with increasing risk with decreasing CD4 T cell count. The majority (median 70%) occur in the first 3 months with the greatest proportion of deaths due to previously undiagnosed tuberculosis (TB). The investigators will enroll patients from 4 geographically diverse countries (Gabon, Mozambique, South Africa, and Uganda) in a randomized open label clinical trial targeting a population of people with high mortality risk; patients with CD4 T cell count < 50 cells/μl and body mass index (BMI) < 18 kg/m2. Severely immunocompromised patients with low BMI in the intervention arm will receive presumptive anti-TB 4-drug chemotherapy and subsequently initiate ART within 2 weeks compared to ART alone. The main objective is to measure and compare early mortality in the group presumptively treated for TB in addition to ART. Other sub-objectives are to determine the predictors of early mortality and the causes of death by autopsy (traditional and verbal), to determine if presumptive anti-TB treatment affects viral suppression with ART, and to assess incidence rates and characterize drug toxicity in patients dually treated. Because of the high rates of TB co-infection in sub-Saharan Africa in the HIV-infected, the investigators expect that patients presumptively treated for TB in addition to HIV will have a lower mortality rate than patients receiving ART only. This trial is expected to be of great public health benefit and generalisability.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Prof JMA Lange
• Collaborator: European and Developing Countries Clinical Trials Partnership (EDCTP)
• Treatments: Efavirenz

Criteria

Inclusion Criteria:

• Aged > 18 years old

• HIV-1 positive

• Eligible for antiretroviral treatment with CD4 T cell count < 50 cells/μl

• BMI < 18

Exclusion Criteria:

• Patients with smear-positive pulmonary TB

• Patients who fulfill the diagnostic criteria for smear-negative pulmonary or extrapulmonary TB (http://www.who.int/tb/publications/2006/tbhiv_recommendations.pdf ).

• Previous TB treatment (history of TB medication for > 1 month

• History of using antiretroviral drugs

• Symptomatic known underlying liver disease or transaminases > 5x upper limit of normal

• Known or suspected drug resistance to more than one first-line TB drug according to WHO criteria but excluding HIV infection (e.g. household contacts of MDRTB patients)

• Pregnant or breast-feeding

• Patients with cryptococcal meningitis (CrAG positive with neurologic symptoms)

• Patients with other severe (opportunistic) disease such as disseminated KS, malignant lymphoma, toxoplasmosis who may not be able to tolerate anti-TB medication or require other specific therapy

• Patients with danger signs (respiratory rate > 30 per minute, heart rate > 120bpm, temperature > 39oC, and unable to ambulate)

• Taking other potentially life-saving medications (e.g. for other OIs, or immunosuppressants) that are incompatible with anti-TB chemotherapy or ART

• Unable to swallow TB medications

• Unable to follow-up at the clinic for regularly scheduled follow-up (e.g. too far from clinic)