Tuberculosis associated mortality in a prospective cohort in Sub Saharan Africa: Association with HIV and antiretroviral therapy.
OBJECTIVE
Nine out of ten tuberculosis deaths occur in tuberculosis-burdened countries, particularly Sub Saharan Africa. In these setting mortality has not been fully described. We describe the magnitude and pattern of TB mortality in Tanzania.


METHODS
A multicenter prospective cohort study was conducted among HIV infected and uninfected pulmonary tuberculosis patients from time of anti-TB treatment initiation to completion. Patients were censored at the time of treatment completion, or at their last visit for those who did not complete TB treatment. Kaplan-Meier curves were used to estimate time to death; cox proportional hazards model was used to examine risk factors for mortality.


RESULTS
A total of 58 deaths out of 1696 patients (3.4%) occurred, two thirds (n=39) during the first two months of treatment. Compared to HIV un-infected TB patients, mortality risk for TB/HIV co-infected patients was least when antiretroviral therapy (ART) was initiated after 14 days of anti-TB (RR=3.55; 95% CI: 1.44, 8.73 p<0.0001) and highest when ART was initiated 90 days or less prior to anti-TB and within the first 14 days of anti-TB therapy (RR=10; 95% CI: 3.28, 30.54; p<0.0001).


CONCLUSIONS
Meticulously planned and supervised antiretroviral therapy reduces mortality among TB/HIV patients. Among patients with TB/HIV naïve of ART, withholding ART until the third week of anti-tuberculosis therapy will likely reduce TB mortality in Tanzania. Patients on ART and later develop tuberculosis should be closely monitored.
Division of Therapeutic Immunology, Department of Laboratory Medicine (LABMED), Karolinska Institutet, and the center for allogeneic stem cell transplantation, (CAST), Karolinska University Hospital, Stockholm, Sweden; Department of Internal Medicine, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
Tumaini J
TJ
Nagu
Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
Said
S
Aboud
Management and development for health (MDH), Dar es Salaam.
Ramadhani
R
Mwiru
Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
Mecky I
MI
Matee
Division of Therapeutic Immunology, Department of Laboratory Medicine (LABMED), Karolinska Institutet, and the center for allogeneic stem cell transplantation, (CAST), Karolinska University Hospital, Stockholm, Sweden.
Martin
M
Rao
Department of Global health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Wafaie W
WW
Fawzi
Division of Infection and Immunity, University College London, and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, United Kingdom, UK.
Alimuddin
A
Zumla
Division of Therapeutic Immunology, Department of Laboratory Medicine (LABMED), Karolinska Institutet, and the center for allogeneic stem cell transplantation, (CAST), Karolinska University Hospital, Stockholm, Sweden. Electronic address: markus.maeurer@ki.se.
Markus J
MJ
Maeurer
Department of Internal Medicine, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
Ferdinand
F
Mugusi
D000293:Adolescent; D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D060085:Coinfection / Q000188:drug therapy; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D014397:Tuberculosis, Pulmonary / Q000150:complications* / Q000188:drug therapy / Q000401:mortality*; D055815:Young Adult
D019380:Anti-HIV Agents; D000995:Antitubercular Agents
ART; ARV; Antiretroviral therapy; HIV; TB; TB/HIV; death; survival; treatment outcome