prevention of early mortality by presumptive tuberculosis (tb) treatment

Conditions: HIV Infection; Tuberculosis

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.


Eligibility 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)

Keywords: tb