Comparison of effects of isoniazid plus ART and ART only regimen on the incidence of tuberculosis and HIV progression in HIV positive patients: a retrospective cohort study at two hospitals in Addis Ababa, Ethiopia

Dumessa Edessa, Tolera Woldeyes, Workineh Shibeshi


Background: Tuberculosis is a major opportunistic complication of HIV-infection. Antiretroviral therapy (ART) lowers incidence of tuberculosis (TB) but may not be sufficient to control HIV-related tuberculosis, implying a need for additional interventions. The aim of this study was to compare the effects of isoniazid preventive therapy (IPT) plus ART and ART only regimens on the incidence of active TB and HIV progression in HIV positive patients.

Methods: The retrospective cohort study was conducted at Tikur Anbessa Specialized Hospital and Zewditu Memorial Hospital on 185 patients receiving IPT plus ART and 557 patients receiving ART only. Incidence rates (IR) were used to determine incidence rates of tuberculosis. Time to AIDS and TB event were compared using student t-test. Risks of the outcomes were identified using regression models.

Results: The study showed a reduced tuberculosis incidence rate from 7.44 to 1.8 cases/100 person-years [PYs] by IPT plus ART compared to ART only. In reference to ART alone, the IPT plus ART significantly reduced risks of active TB (adjusted odds ratio [AOR] 0.24; 95% CI 0.09–0.63; P=0.004) and had about 16 months of TB protection (P<0.001). In addition, the IPT plus ART delayed HIV progression to AIDS more significantly than the ART only (P=0.029). However, it increased risks of adverse events (AOR 3.33; 95% CI 1.35–8.19; P=0.01) more than the ART only.

Conclusions: The wider use of IPT with ART impacts more on incidence of tuberculosis and time to AIDS while simultaneously increasing risks of adverse events than the ART only. 


Antiretroviral therapy, HIV-infected, Tuberculosis, Isoniazid preventive therapy

Full Text:



Golub JE, Saraceni V, Cavalcante SC, Antonio G, Pacheco AG, Moultona LH, et al. The impact of antiretroviral therapy and Isoniazid preventive therapy on tuberculosis incidence in HIV-infected patients in Rio de Janeiro, Brazil. AIDS. 2007;21 (11):1441–8.

Frigati LJ, Kranzer K, Cotton MF, Schaaf HS, Lombard CJ, Zar HJ. The impact of isoniazid preventive therapy and antiretroviral therapy on tuberculosis in children infected with HIV in a high tuberculosis incidence setting. Thorax. 2011;66:496–501.

Martinson N, Hoffmann C, and Chaisson R. Epidemiology of Tuberculosis and HIV: Recent Advances in Understanding and Responses. Proc Am Thorac Soc. 2010;8: 288–93.

Akolo C, Adetifa I, Shepperd S, Volmink J. Treatment of latent tuberculosis infection in HIV infected persons. The Cochrane Collaboration. 2010;1:1–81.

Vieira de Souza CT, Hökerberg YHM, Pacheco SJB, Rolla VC, Passos SRL. Effectiveness and safety of isoniazid chemoprophylaxis for HIV-1 infected patients from Rio de Janeiro. Mem Inst Oswaldo Cruz. 2009;104 (3):462–7.

Lawn SD, Wood R and Wilkinson RJ. Changing Concepts of “Latent Tuberculosis Infection” in Patients Living with HIV Infection. Clinical and Developmental Immunology. 2010;2011:1–9.

Pawlowski A, Jansson M, Skold M, Rottenberg ME, Ka llenius G. Tuberculosis and HIV Co-Infection. PLoS Pathogens. 2012;8(2):1–7.

Chamie G, Luetkemeyer A, Charlebois E, and Havlir DV. Tuberculosis as Part of the Natural History of HIV Infection in Developing Countries. Clin Infect Dis. 2010;50(3): S245–54.

Lawn SD, Ayles H, Egwaga S, Williams B, Mukadi YD, Filho EDS, et al. Potential utility of empirical tuberculosis treatment for HIV-infected patients with advanced immunodeficiency in high TB-HIV burden settings. Int J Tuberc Lung Dis. 2011;15(3):287–95.

Frothingham R, Stout JE, Hamilton CD. Current issues in global tuberculosis control. International Society for Infectious Diseases. 2005;9:297–311.

Meya DB and McAdam KPWJ. The TB pandemic: an old problem seeking new solutions. J Intern Med. 2007;261:309–29.

Sabina Mugusi. Optimization of HIV and tuberculosis co-treatment in Tanzania: drug-drug interactions and clinical outcomes. 2013;1 – 17.

Loeffler AM. Pediatric Tuberculosis. Seminars in Respiratory Infection. 2003;18(4):272–91.

Swaminathan S, Menon PA, Gopalan N, Perumal V, Santhanakrishnan RK, Ramachandran R, et al. Efficacy of a Six-Month versus a 36-Month Regimen for Prevention of Tuberculosis in HIV-Infected Persons in India: A Randomized Clinical Trial. PLoS ONE. 2012;7(12):1–9.

Golub JE, Astemborski J, Ahmed M, Cronin W, Mehta SH, Kirk GD, et al. Long-term effectiveness of diagnosing and treating latent tuberculosis infection in a cohort of HIV-infected and at risk injection drug users. J Acquir Immune Defic Syndr. 2008;49(5):532–7.

Montaner JSG, Hogg R, Wood E, Kerr T, Tyndall M, Levy AR, et al. The case for expanding access to highly active antiretroviral therapy to curb the growth of the HIV epidemic. Lancet. 2006;368:531–6.

Rhatigan J, Jain S, Mukherjee JS, and Porter ME. Applying the Care Delivery Value Chain: HIV/AIDS Care in Resource Poor Settings. Global Health Delivery Project. 2009;1–13.

Mosimaneotsile B, Mathoma A, Chengeta B, Nyirenda S, Agizew TB, Tedla Z, et al. Isoniazid Tuberculosis Preventive Therapy in HIV-Infected Adults Accessing Antiretroviral Therapy: A Botswana Experience, 2004–2006. J Acquir Immune Defic Syndr. 2010;54:71–7.

Grant AD, Charalambous S, Fielding KL, Day JH, Corbett EL, Chaisson RE, et al. Effect of Routine Isoniazid Preventive Therapy on Tuberculosis Incidence among HIV-Infected Men in South Africa: A Novel Randomized Incremental Recruitment Study. JAMA. 2005;293(22):2719–25.

Sonnenberg P, Glynn JR, Fielding K, Murray J, Godfrey-Faussett P, and Shearer S. How Soon after Infection with HIV Does the Risk of Tuberculosis Start to Increase? A Retrospective Cohort Study in South African Gold Miners. JID. 2005;191:150–8.

Lawn SD, Myer L, Edwards D, Bekkera LG and Wood R. Short-term and long-term risk of tuberculosis associated with CD4 cell recovery during antiretroviral therapy in South Africa. AIDS. 2009;23:1717–25.

Lawn SD, Myer L, Edwards D, Bekkera LG and Wood R. Burden of tuberculosis in an antiretroviral treatment programme in sub-Saharan Africa: impact on treatment outcomes and implications for tuberculosis control. AIDS. 2006;20:1605–12.

Lawn SD, Myer L, Edwards D, Bekkera LG and Wood R. Short-term and long-term risk of tuberculosis associated with CD4 cell recovery during antiretroviral therapy in South Africa. AIDS. 2009;23:1717–25.

Komati S, Shaw PA, Stubbs N, Mathibedi MJ, Malan L, Sangweni P, et al. Tuberculosis risk factors and mortality for HIV-infected persons receiving antiretroviral therapy in South Africa. AIDS. 2010;24:1849–55.

Maher D, Harries A, and Getahun H. Tuberculosis and HIV interaction in sub-Saharan Africa: impact on patients and programmes; implications for policies. Tropical Medicine and International Health. 2005;10(8):734–42.

Fawzi WW, Msamanga G, Spiegelman D, Wei R, Kapiga S, Villamor E, et al. Randomized Trial of Multivitamin Supplements and HIV Disease Progression and Mortality. N Engl J Med. 2004;351(1):23–32.

Selwyn PA, Algabes P, Hartel D, Buono D, Schoenbaun EE, Klein RS, et al. Clinical Manifestations and Predictors of disease progression in drug users with HIV infection. N Engl J Med. 1992;327(24):1698–1703.

Farzadegan H, Hoover DH, Astemborski J, Lyles CM, Margolick JB, Markham RB, et al. Sex differences in HIV-1 viral load and progression to AIDS. The Lancet. 1998;352:1510–14.

Webber MP, Schoenbaum EE, Gourevitch MN, Buono D and Klein RS. A prospective study of HIV disease progression in female and male drug users. AIDS. 1999;13:257–62.

Samet JH, Cheng DM, Libman H, Nunes DP, Alperen JK, and Saitz R. Alcohol Consumption and HIV Disease Progression. J Acquir Immune Defic Syndr. 2007;46(2):194–9.

Gore-Felton C, and Koopman C. Behavioral Mediation of the Relationship between Psychosocial Factors and HIV Disease Progression. Psychosomatic Medicine. 2008;70:569–74.

Furber AS, Maheswaran R, Newell JN, and Carroll C. Is smoking tobacco an independent risk factor for HIV infection and progression to AIDS? A systemic review. Sex Transm Infect 2007;83:41–6.

Gutierrez EB, Gomes V, Picone CM, Suga H and Atomiya AN. Active tuberculosis and Mycobacterium tuberculosis latent infection in patients with HIV/AIDS. HIV Medicine. 2009;10:564–72.

Bucher HC, Griffith LE, Guyatt GH, Sudre P, Naef M, Pedram Sendi P, et al. Isoniazid prophylaxis for tuberculosis in HIV infection: a meta-analysis of randomized controlled trials. AIDS. 1999;13:501–7.

Wilkinson D. Drugs for preventing tuberculosis in HIV infected persons. The Cochrane Library 2003;(4):1–6.