Natural History and Factors Associated with Early and Delayed Mortality in HIV-Infected Patients Treated of Tuberculosis under Directly Observed Treatment Short-Course Strategy: A Prospective Cohort Study in India

Gerardo Alvarez-Uria, Praveen Kumar Naik, Raghavakalyan Pakam, Lakshminaryana Bachu, Manoranjan Midde, Gerardo Alvarez-Uria, Praveen Kumar Naik, Raghavakalyan Pakam, Lakshminaryana Bachu, Manoranjan Midde

Abstract

Despite the impressive global results of DOTS in India, the effectiveness of DOTS for the treatment of tuberculosis in HIV-infected patients is not well known. This is an observational prospective cohort study performed in Anantapur District, Andhra Pradesh, India. The study included 1000 DOTS antituberculosis treatment (ATT) episodes and 840 person-years. CD4 lymphocyte count was below 200 cells/mm(3) in 77% of the cases, and 21% were retreatments. Two thirds were presented with extrapulmonary tuberculosis, and the most common form of extrapulmonary tuberculosis was tuberculous meningitis followed by pleuritis, abdominal tuberculosis, and lymphadenitis. Cumulative incidence of mortality was 16%, 26%, 39%, and 46% at 1, 3, 12, and 24 months, respectively. Factors associated with three-month (early) mortality were being homeless, having low CD4+ lymphocyte count, having tuberculous meningitis, belonging to a socially disadvantaged community, having more than 35 years, and being on an antiretroviral therapy at the moment of initiating the ATT. Factors associated with delayed mortality were having low CD4+ lymphocyte count, belonging to a socially disadvantaged community, receiving a category II ATT because of a previous episode of ATT and having acid fast bacilli in sputum before the ATT initiation. These findings indicate that there is an urgent need to improve the treatment of tuberculosis in HIV-infected patients in India.

Figures

Figure 1
Figure 1
Kaplan-Meier survival curves of all patients and by type of tuberculosis. AFB: acid fast bacilli; CI: confidence interval.
Figure 2
Figure 2
Kaplan-Meier survival curves by age, gender, literacy, being homeless, community, CD4+ lymphocyte count (cells/mm3), presence of AFB+ sputum, type of antituberculosis treatment, and timing of the antiretroviral therapy. (AFB: acid fast bacilli; ART: antiretroviral therapy; ATT: antituberculosis treatment; OC/BC: nondisadvantaged communities: other castes and backward castes; ST/SC, disadvantaged communities: scheduled tribes, scheduled castes.)

References

    1. WHO. Global Tuberculosis Control. 2011.
    1. WHO. Progress Report 2011: Global HIV/AIDS Response. 2011.
    1. Kwan CK, Ernst JD. HIV and tuberculosis: a deadly human syndemic. Clinical Microbiology Reviews. 2011;24(2):351–376.
    1. Schutz C, Meintjes G, Almajid F, Wilkinson RJ, Pozniak A. Clinical management of tuberculosis and HIV-1 co-infection. European Respiratory Journal. 2010;36(6):1460–1481.
    1. WHO. Treatment of Tuberculosis: Guidelines For National Programmes. 3rd edition. 2003. WHO/CDS/TB/2003.313.
    1. Tiwari P, Soneja M, Sharma SK. Tuberculosis management—time for paradigm shift? Indian Journal of Tuberculosis. 2011;58:97–101.
    1. Tripathy S, Anand A, Inamdar V, et al. Clinical response of newly diagnosed HIV seropositive & seronegative pulmonary tuberculosis patients with the RNTCP short course regimen in Pune, India. Indian Journal of Medical Research. 2011;133(5):521–528.
    1. Swaminathan S, Narendran G, Venkatesan P, et al. Efficacy of a 6-month versus 9-month intermittent treatment regimen in HIV-infected patients with tuberculosis: a randomized clinical trial. American Journal of Respiratory and Critical Care Medicine. 2010;181(7):743–751.
    1. UNAIDS/WHO. Country Progress Report. UNGASS; 2010.
    1. Alvarez-Uria G, Midde M, Naik PK. Trends and risk factors for HIV infection among young pregnant women in rural India. International Journal of Infectious Diseases. 2012;16(2):e121–e123.
    1. Alvarez-Uria G, Midde M, Pakam R, Naik PK. Gender differences, routes of transmission, socio-demographic characteristics and prevalence of HIV related infections of adults and children in an HIV cohort from a rural district of India. Infectious Disease Reports. 2012;4(1):p. e19.
    1. Tarantino L, Giorgio A, de Stefano G, Farella N, Perrotta A, Esposito F. Disseminated mycobacterial infection in AIDS patients: abdominal US features and value of fine-needle aspiration biopsy of lymph nodes and spleen. Abdominal Imaging. 2003;28(5):602–608.
    1. Sharma SK, Smith-Rohrberg D, Tahir M, Mohan A, Seith A. Radiological manifestations of splenic tuberculosis: a 23-patient case series from India. Indian Journal of Medical Research. 2007;125(5):669–678.
    1. WHO. Treatment of Tuberculosis: Guidelines for National Programmes. 4th edition 2010.
    1. WHO. Antiretroviral Therapy for HIV Infection in Adults and Adolescents. 2006.
    1. Ministry of Health and Family Welfare India. Technical and Operational Guideline for Tuberculosis Control. 2005.
    1. Alvarez-Uria G, Midde M, Naik PK. Socio-demographic risk factors associated with HIV infection in patients seeking medical advice in a rural hospital of India. Journal of Public Health Research. 2012;1(1):p. e14.
    1. Schonlau M. Boosted regression (boosting): an introductory tutorial and a Stata plugin. Stata Journal. 2005;5(3):330–354.
    1. Kleinbaum DG, Klein M. Survival Analysis, a Self-Learning Text. 2nd edition. New York, NY, USA: Springer; 2005.
    1. Harrell FE, Califf RM, Pryor DB, Lee KL, Rosati RA. Evaluating the yield of medical tests. The Journal of the American Medical Association. 1982;247:2543–2546.
    1. Kleinbaum DG, Klein M, Pryor ER. Logistic Regression: A Self-learning Text. New York, NY, USA: Springer; 2010.
    1. Sanchez M, Bartholomay P, Arakaki-Sanchez D, et al. Outcomes of TB treatment by HIV status in national recording systems in Brazil, 2003–2008. PLoS One. 2012;7e33129
    1. Thuy TT, Shah NS, Anh MH, et al. HIV-associated TB in an giang province, Vietnam, 2001–2004: epidemiology and TB treatment outcomes. PloS One. 2007;2(6):p. e507.
    1. Mukadi YD, Maher D, Harries A. Tuberculosis case fatality rates in high HIV prevalence populations in sub-Saharan Africa. AIDS. 2001;15(2):143–152.
    1. Straetemans M, Bierrenbach AL, Nagelkerke N, Glaziou P, van der Werf MJ. The effect of tuberculosis on mortality in HIV positive people: a meta-analysis. PLoS One. 2010;5(12)e15241
    1. Gopi PG, Vasantha M, Muniyandi M, Chandrasekaran V, Balasubramanian R, Narayanan PR. Risk factors for non-adherence to directly observed treatment (DOT) in a rural tuberculosis unit, South India. The Indian Journal of Tuberculosis. 2007;54(2):66–70.
    1. Jha UM, Satyanarayana S, Dewan PK, et al. Risk factors for treatment default among re-treatment tuberculosis patients in India, 2006. PLoS One. 2010;5(1)e8873
    1. Dasgupta R, Ghanashyam I. Connecting the DOTS: spectre of a public health iatrogenesis? Indian Journal of Community Medicine. 2012;37(1):13–15.
    1. Khan FA, Minion J, Pai M, et al. Treatment of active tuberculosis in HIV-coinfected patients: a systematic review and meta-analysis. Clinical Infectious Diseases. 2010;50(9):1288–1299.
    1. Alvarez-Uria G, Midde M, Pakam R, Kannan S, Bachu L, Naik PK. Factors associated with late presentation of HIV and estimation of antiretroviral treatment need according to CD4 lymphocyte count in a resource-limited setting: data from an HIV cohort study in India. Interdisciplinary Perspectives on Infectious Diseases. 2012;2012:7 pages.293795
    1. Mojumdar K, Vajpayee M, Chauhan NK, Mendiratta S. Late presenters to HIV care and treatment, identification of associated risk factors in HIV-1 infected Indian population. BMC Public Health. 2010;10, article 416
    1. Waitt CJ, Squire SB. A systematic review of risk factors for death in adults during and after tuberculosis treatment. International Journal of Tuberculosis and Lung Disease. 2011;15(7):871–885.
    1. Santha T, Garg R, Frieden TR, et al. Risk factors associated with default, failure and death among tuberculosis patients treated in a DOTS programme in Tiruvallur District, South India, 2000. International Journal of Tuberculosis and Lung Disease. 2002;6(9):780–788.
    1. Koenig SP, Riviere C, Leger P, et al. High mortality among patients with AIDS who received a diagnosis of tuberculosis in the first 3 months of antiretroviral therapy. Clinical Infectious Diseases. 2009;48(6):829–831.
    1. Alvarez-Uria G, Azcona JM, Midde M, Naik PK, Reddy S, Reddy R. Rapid diagnosis of pulmonary and extrapulmonary tuberculosis in HIV-infected patients. Comparison of LED fluorescent microscopy and the geneXpert MTB/RIF assay in a district hospital in India. Tuberculosis Research and Treatment. 2012;2012:4 pages.932862

Source: PubMed

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