Outcomes among HIV-1 Infected Individuals First Starting Antiretroviral Therapy with Concurrent Active TB or Other AIDS-Defining Disease

Background Tuberculosis (TB) is common among HIV-infected individuals in many resource-limited countries and has been associated with poor survival. We evaluated morbidity and mortality among individuals first starting antiretroviral therapy (ART) with concurrent active TB or other AIDS-defining disease using data from the “Prospective Evaluation of Antiretrovirals in Resource-Limited Settings” (PEARLS) study. Methods Participants were categorized retrospectively into three groups according to presence of active confirmed or presumptive disease at ART initiation: those with pulmonary and/or extrapulmonary TB (“TB” group), those with other non-TB AIDS-defining disease (“other disease”), or those without concurrent TB or other AIDS-defining disease (“no disease”). Primary outcome was time to the first of virologic failure, HIV disease progression or death. Since the groups differed in characteristics, proportional hazard models were used to compare the hazard of the primary outcome among study groups, adjusting for age, sex, country, screening CD4 count, baseline viral load and ART regimen. Results 31 of 102 participants (30%) in the “TB” group, 11 of 56 (20%) in the “other disease” group, and 287 of 1413 (20%) in the “no disease” group experienced a primary outcome event (p = 0.042). This difference reflected higher mortality in the TB group: 15 (15%), 0 (0%) and 41 (3%) participants died, respectively (p<0.001). The adjusted hazard ratio comparing the “TB” and “no disease” groups was 1.39 (95% confidence interval: 0.93–2.10; p = 0.11) for the primary outcome and 3.41 (1.72–6.75; p<0.001) for death. Conclusions Active TB at ART initiation was associated with increased risk of mortality in HIV-1 infected patients.

[1]  M. Wulfsohn,et al.  Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings , 2012, PLoS medicine.

[2]  C. Giaquinto,et al.  Polymorphisms of innate immunity genes influence disease progression in HIV-1-infected children , 2012, AIDS.

[3]  M. Plana,et al.  Very late initiation of HAART impairs treatment response at 48 and 96 weeks: results from a meta-analysis of randomized clinical trials. , 2012, The Journal of antimicrobial chemotherapy.

[4]  G. d’Ettorre,et al.  Rate and determinants of treatment response to different antiretroviral combination strategies in subjects presenting at HIV-1 diagnosis with advanced disease , 2011, BMC infectious diseases.

[5]  Lerato Mohapi,et al.  Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. , 2011, The New England journal of medicine.

[6]  J. Montaner,et al.  Antiretroviral Therapy in Prevention of HIV and TB: Update on Current Research Efforts , 2011, Current HIV research.

[7]  B. Hernández-Novoa,et al.  Response to HAART in treatment-naive HIV-infected patients with a prior diagnosis of tuberculosis or other opportunistic infections. , 2011, Current HIV research.

[8]  S. Lawn,et al.  Optimum time to start antiretroviral therapy during HIV-associated opportunistic infections , 2011, Current Opinion in Infectious Diseases.

[9]  N. Nagelkerke,et al.  The Effect of Tuberculosis on Mortality in HIV Positive People: A Meta-Analysis , 2010, PloS one.

[10]  W. El-Sadr,et al.  Timing of initiation of antiretroviral drugs during tuberculosis therapy. , 2010, The New England journal of medicine.

[11]  A. Zolopa,et al.  Early Antiretroviral Therapy Reduces AIDS Progression/Death in Individuals with Acute Opportunistic Infections: A Multicenter Randomized Strategy Trial , 2009, PloS one.

[12]  Ross J. Harris,et al.  Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[13]  C. Barros,et al.  Effect of Simultaneous Use of Highly Active Antiretroviral Therapy on Survival of HIV Patients With Tuberculosis , 2009, Journal of acquired immune deficiency syndromes.

[14]  W. Manosuthi,et al.  Survival Rate and Risk Factors of Mortality Among HIV/Tuberculosis-Coinfected Patients With and Without Antiretroviral Therapy , 2006, Journal of acquired immune deficiency syndromes.

[15]  Milton C Weinstein,et al.  The survival benefits of AIDS treatment in the United States. , 2006, The Journal of infectious diseases.

[16]  Fernando Aiuti,et al.  Failure to reconstitute CD4+ T-cells despite suppression of HIV replication under HAART. , 2006, AIDS reviews.

[17]  I. Pešić,et al.  The prevalence and risk of immune restoration disease in HIV‐infected patients treated with highly active antiretroviral therapy , 2005, HIV medicine.

[18]  P. Price,et al.  Immune restoration disease after antiretroviral therapy , 2004, AIDS.

[19]  A. Mocroft,et al.  Decline in the AIDS and death rates in the EuroSIDA study: an observational study , 2003, The Lancet.

[20]  Christopher Dye,et al.  The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. , 2003, Archives of internal medicine.

[21]  J. J. Henning,et al.  Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, January 28, 2000 , 1998, HIV clinical trials.

[22]  髙折 晃史,et al.  19th Conference on Retroviruses and Opportunistic Infections , 2012 .

[23]  B. Stilwell,et al.  Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach. 2006 revision. , 2006 .

[24]  C. Sabin The changing clinical epidemiology of AIDS in the highly active antiretroviral therapy era , 2002, AIDS.