Burden of tuberculosis in an antiretroviral treatment programme in sub-Saharan Africa: impact on treatment outcomes and implications for tuberculosis control

Objectives:To determine burden and risk factors for tuberculosis (TB) in an antiretroviral treatment (ART) programme and its impact on ART outcomes. Design:Prospective cohort study. Methods:Prevalent TB was assessed at baseline and incident TB was ascertained prospectively over 3 years among 944 patients accessing a community-based ART programme in South Africa. Results:At enrollment, median CD4 cell count was 96 cells/μl and 52% of patients had a previous history of TB. Prevalent TB (current antituberculosis treatment or active TB) was present in 25% and was strongly associated with advanced immunodeficiency. During 782 person-years of ART, 81 cases of TB were diagnosed. The incidence was 22.1/100 person-years during the first 3 months of ART and decreased to an average of 4.5/100 person-years during the second and third years. In multivariate analysis, risk of incident TB during follow-up was only associated with the current absolute CD4 cell count at that time point; an increase of 100 cells/μl was associated with a 25% lower risk (P = 0.007). Although prevalent and incident TB were associated with greater than two-fold increased mortality risk, they did not compromise immunological and virological outcomes among survivors at 48 weeks. Conclusions:Late initiation of ART was associated with a major burden of TB in this ART programme. TB reduced survival but did not impair immunovirological outcomes. Reductions in TB incidence during ART were dependent on CD4 cell count; however, after 3 years of treatment, rates were still 5- to 10-fold higher than among non-HIV-infected people. Earlier initiation of ART may reduce this burden of TB.

[1]  S. Lawn,et al.  Incidence of tuberculosis during highly active antiretroviral therapy in high-income and low-income countries. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[2]  L. Myer,et al.  CD4 cell count recovery among HIV-infected patients with very advanced immunodeficiency commencing antiretroviral treatment in sub-Saharan Africa , 2006, BMC infectious diseases.

[3]  L. Myer,et al.  Early mortality among adults accessing a community-based antiretroviral service in South Africa: implications for programme design , 2005, AIDS.

[4]  L. Myer,et al.  Impact of HIV infection on the epidemiology of tuberculosis in a peri-urban community in South Africa: the need for age-specific interventions. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[5]  A. Telenti,et al.  CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. , 2003, Archives of internal medicine.

[6]  L. Myer,et al.  Efficacy of antiretroviral therapy in resource-poor settings: are outcomes comparable to those in the developed world? , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[7]  N. Ives,et al.  Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy , 2002, AIDS.

[8]  B. Marston,et al.  Tuberculosis in sub-Saharan Africa: opportunities, challenges, and change in the era of antiretroviral treatment , 2006, The Lancet.

[9]  M. Lederman,et al.  CD4+ T-lymphocyte nadir and the effect of highly active antiretroviral therapy on phenotypic and functional immune restoration in HIV-1 infection. , 2002, Clinical immunology.

[10]  N. Breslow,et al.  Statistical methods in cancer research. Volume II--The design and analysis of cohort studies. , 1987, IARC scientific publications.

[11]  S. Lawn,et al.  How effectively does HAART restore immune responses to Mycobacterium tuberculosis? Implications for tuberculosis control , 2005, AIDS.

[12]  Norman E. Breslow,et al.  Statistical Methods in Cancer Research, Vol. II: The Design and Analysis of Cohort Studies. , 1990 .

[13]  E. Messou,et al.  Risk factors for active tuberculosis after antiretroviral treatment initiation in Abidjan. , 2005, American journal of respiratory and critical care medicine.

[14]  L. Myer,et al.  Determinants of mortality and nondeath losses from an antiretroviral treatment service in South Africa: implications for program evaluation. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[15]  Brian G. Williams,et al.  Antiretroviral Drugs for Tuberculosis Control in the Era of HIV/AIDS , 2003, Science.

[16]  G. Maartens,et al.  Risk Factors for Developing Tuberculosis in HIV‐1‐Infected Adults From Communities With a Low or Very High Incidence of Tuberculosis , 2000, Journal of acquired immune deficiency syndromes.

[17]  R. Wood,et al.  Effect of highly active antiretroviral therapy on incidence of tuberculosis in South Africa: a cohort study , 2002, The Lancet.

[18]  B. Everitt,et al.  Analysis of longitudinal data , 1998, British Journal of Psychiatry.

[19]  S. Lawn,et al.  Immune reconstitution disease associated with mycobacterial infections in HIV-infected individuals receiving antiretrovirals. , 2005, The Lancet. Infectious diseases.

[20]  S. Lawn,et al.  How can earlier entry of patients into antiretroviral programs in low-income countries be promoted? , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[21]  S. Lawn,et al.  Tuberculosis among HIV-infected patients receiving HAART: long term incidence and risk factors in a South African cohort , 2005, AIDS.

[22]  J. Cuzick A Wilcoxon-type test for trend. , 1985, Statistics in medicine.

[23]  J. Cuzick,et al.  A Wilcoxon-type test for trend. , 1985, Statistics in medicine.

[24]  P. Small,et al.  Clinical management of tuberculosis in the context of HIV infection. , 2004, Annual review of medicine.