Incidence and Predictors of Mortality and the Effect of Tuberculosis Immune Reconstitution Inflammatory Syndrome in a Cohort of TB/HIV Patients Commencing Antiretroviral Therapy

Worodria, William MMed*†‡; Massinga-Loembe, Marguerite PhD§; Mazakpwe, Doreen MBChB‡; Luzinda, Kenneth MBChB‡; Menten, Joris MSc§; Van Leth, Frank MD, PhD‖¶; Mayanja-Kizza, Harriet MBChB, MMed, MSc*‡; Kestens, Luc PhD†§; Mugerwa, Roy D MBChB, MMed*‡; Reiss, Peter MD, PhD‖; Colebunders, Robert MD, PhD‡#**; For the TB-IRIS Study Group

JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e3182255dc2
Clinical Science
Abstract

Background: Tuberculosis-HIV (TB-HIV) coinfection remains an important cause of mortality in antiretroviral therapy (ART) programs. In a cohort of TB-HIV-coinfected patients starting ART, we examined the incidence and predictors of early mortality.

Methods: Consecutive TB-HIV-coinfected patients eligible for ART were enrolled in a cohort study at the Mulago National Tuberculosis and Leprosy Program clinic in Kampala, Uganda. Predictors of mortality were assessed using Cox proportional hazards analysis.

Results: Three hundred and two patients [median CD4 count 53 cells/μL (interquartile range, 20-134)] were enrolled. Fifty-three patients died, 36 (68%) of these died within the first 6 months of TB diagnosis. Male sex [hazard (HR): 2.19; 95% confidence interval (CI): 1.19 to 4.03; P = 0.011], anergy to tuberculin skin test [HR: 2.59 (1.10 to 6.12); P = 0.030], a positive serum cryptococcal antigen result at enrollment (HR: 4.27; 95% CI: 1.50 to 12.13; P = 0.006) and no ART use (HR: 4.63; 95% CI: 2. 37 to 9.03; P < 0.001) were independent predictors of mortality by multivariate analysis. Six (10%) patients with TB immune reconstitution inflammatory syndrome died, and in most, an alternative contributing cause of death was identified.

Conclusions: Mortality among these TB-HIV-coinfected patients was high particularly when presenting with advanced HIV disease and not starting ART, reinforcing the need for timely and joint treatment for both infections. Screening for a concomitant cryptococcal infection and antifungal treatment for patients with cryptococcal antigenemia may further improve clinical outcome.

Author Information

From the *Department of Medicine, Makerere University College of Health Sciences, Mulago Hospital, Kampala, Uganda; †Department of Medical Sciences, University of Antwerp, Antwerp, Belgium; ‡Infectious diseases Network for Treatment and Research in Africa, Kampala, Uganda; §Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium; ‖Academic Medical Centre, Department of Global Health and Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands; ¶KNCV Tuberculosis Foundation, The Hague, The Netherlands; #Department of Epidemiology and Social Medicine, University of Antwerp, Antwerp, Belgium; and **Department of Clinical Sciences Institute of Tropical Medicine, Antwerp, Belgium.

Received for publication January 16, 2011; accepted May 19, 2011.

Supported by Netherlands Organization for Scientific Research—WOTRO Science for Global Development, grant NACCAP W 07.05.20100; EC FP6 Specific Targeted Research Project (STREP) grant LSHP-CT-2007-037659-TBIRIS. This work was done as part of the Infectious Diseases Network for Treatment and Research in Africa (INTERACT).

Presented on: “Risk factors for early mortality in a cohort of TB-HIV patients commencing antiretroviral therapy” at the 41st Union World Conference on Lung Health, November 11-15, 2010, Berlin, Germany.

The members of TB-IRIS study group are listed in Appendix I.

The authors have no conflicts of interest to disclose.

Correspondence to: Dr William Worodria, MMed, Department of Medicine, Mulago Hospital, PO Box 7051, Kampala, Uganda (e-mail: worodria@yahoo.com).

© 2011 Lippincott Williams & Wilkins, Inc.