Times of initiation of antiretroviral therapy in patients with tuberculosis and human immunodeficiency virus co-infection with CD4 count less than 350 cells/mm3
Abstract
OBJECTIVE
To examine the mortality rates of various initiation times of antiretroviral therapy (ART) after starting tuberculosis treatment.
METHODS
We conducted a retrospective cohort study using medical records of outpatients with the diagnosis of TB/HIV co-infection in Khon Kaen Hospital, Thailand between January 2007 and August 2017. We included the patients who started tuberculosis treatment and various times of starting ART with CD4 count less than 350 cells/mm3. We separated patients into 3 groups by the time of initiated ART starting within the first 4 weeks, 5 to 8 weeks, and 9 to12 weeks after starting tuberculosis treatment. We compared the risk of all-cause mortality within 1 year after start tuberculosis treatment among three groups as our primary outcome. Our secondary outcomes were sputum conversion at 2 months after starting tuberculosis treatment and rate of CD4 count increasing in 1 year after tuberculosis treatment.
RESULTS
A total of 132 patients with TB/HIV co-infection and CD4 count less than 350 cells/mm3 were included in the study; 62 patients started ART within the first 4 weeks after TB treatment, 45 patients started in 5 to 8 weeks and 25 patients started in 9 to 12 weeks. The primary outcome was reached by 1 (2%) patient in the first group, 2 (8%) patients in the second group, and 1 (4%) patient in the third group. (relative risk [RR], 2.76, 95% CI, 0.26 to 29.47 and RR, 2.48, 95% CI, 0.16 to 38.13). Only 28 of 132 patients (21%) had been recorded data on sputum conversion at 2 months after tuberculosis treatment, the result showed no significant difference in improving sputum conversion between starting ART at 5 to 8 weeks and starting ART within the first 4 weeks (RR, 1.30, 95% CI, 0.77 to 2.21). CD4 level increasing rates among the three groups were not significantly different (mean difference (MD), 2556.79, 95% CI, -1011.56 to 6125.14 and MD, 86.67, 95% CI, -1333.69 to 1507.04).
CONCLUSION
The study showed no significant difference between mortality rate and various initiation time of ART after start tuberculosis treatment.
References
World Health Organization (WHO). Global Tuberculosis Report 2015.www.who.int/tb/publications/global_report/en/
Lawn SD, Myer L, Edwards D, Bekker L-G, Wood R. Short-term and long-term risk of tuberculosis associated with CD4 cell recovery during antiretroviral therapy in South Africa. AIDS Lond Engl. 2009 Aug 24;23(13):1717–25.
Kwan CK, Ernst JD. HIV and tuberculosis: a deadly human syndemic. Clin Microbiol Rev. 2011 Apr;24(2):351–76.
Uthman OA, Okwundu C, Gbenga K, Volmink J, Dowdy D, Zumla A, et al. Optimal Timing of Antiretroviral Therapy Initiation for HIV-Infected Adults With Newly Diagnosed Pulmonary Tuberculosis: A Systematic Review and Meta-analysis. Ann Intern Med. 2015 Jul 7;163(1):32.
Mfinanga SG, Kirenga BJ, Chanda DM, Mutayoba B, Mthiyane T, Yimer G, et al. Early versus delayed initiation of highly active antiretroviral therapy for HIV-positive adults with newly diagnosed pulmonary tuberculosis (TB-HAART): a prospective, international, randomised, placebo-controlled trial. Lancet Infect Dis. 2014 Jul 1;14(7):563–71.
Blanc F-X, Sok T, Laureillard D, Borand L, Rekacewicz C, Nerrienet E, et al. Earlier versus Later Start of Antiretroviral Therapy in HIV-Infected Adults with Tuberculosis. N Engl J Med. 2011 Oct 20;365(16):1471–81.
Manosuthi W, Mankatitham W, Lueangniyomkul A, Thongyen S, Likanonsakul S, Suwanvattana P, et al. Time to initiate antiretroviral therapy between 4 weeks and 12 weeks of tuberculosis treatment in HIV-infected patients: results from the TIME study. J Acquir Immune Defic Syndr 1999. 2012 Aug 1;60(4):377–83.
Velasco M, Castilla V, Sanz J, Gaspar G, Condes E, Barros C, et al. Effect of simultaneous use of highly active antiretroviral therapy on survival of HIV patients with tuberculosis. J Acquir Immune Defic Syndr 1999. 2009 Feb 1;50(2):148–52.
Torok ME, Yen NT, Chau TT, et al. Timing of initiation of antiretroviral therapy in human immunodefi ciency virus (HIV)-associated tuberculous meningitis. Clin Infect Dis 2011;52: 1374–83.
Havlir DV, Kendall MA, Ive P, et al. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med 2011; 365: 1482–91.
Braitstein P, Brinkhof MW, Dabis F, et al. Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet 2006; 367: 817–24.
Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray AL, et al. Integration of Antiretroviral Therapy with Tuberculosis Treatment. New England Journal of Medicine. 2011 Oct 20;365(16):1492–501.
Badri M, Wilson D, Wood R. Effect of highly active antiretroviral therapy on incidence of tuberculosis in South Africa: a cohort study. Lancet 2002; 359:2059–64.
Kirk O, Gatell JM, Mocroft A, et al. Infections with Mycobacterium tuberculosis and Mycobacterium avium among HIV-infected patients after the introduction of highly active antiretroviral therapy. Am J Respir Crit Care Med 2000; 162:865–72.
Dean GL, Edwards SG, Ives NJ, et al. Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy. AIDS 2002; 16:75–83.
Pedral-Sampaio DB, Alves CR, Netto EM, Brites C, Oliveira AS, Badaro R. Efficacy and safety of efavirenz in HIV patients on rifampin for tuberculosis. Braz J Infect Dis 2004; 8:211–6.
Lawn SD, Bekker L-G, Miller RF. Immune reconstitution disease associated with mycobacterial infections in HIV-infected individuals receiving antiretrovirals. Lancet Infect Dis 2005; 5:361–73.
Li J, Munsiff SS, Driver CR, Sackoff J. Relapse and acquired rifampin resistance in HIV-infected patients with tuberculosis treated with rifampin or rifabutin-based regimens in New York City, 1997–2000. Clin Infect Dis 2005; 41:83–91.
Vernon A, Burman W, Benator D, Khan A, Bozeman L. Acquired rifamycin monoresistance in patients with HIV-related tuberculosis treated with once-weekly rifapentine and isoniazid. Lancet 1999; 353: 1843–7.
McIlleron H, Wash P, Burger A, Norman J, Folb PI, Smith P. Determinants of rifampicin, isoniazid, pyrazinamide and ethambutol pharmacokinetics in a cohort of tuberculosis patients. Antimicrob Agents Chemother 2006; 50:1170–7.
Weiner M, Benator D, Burman W, et al. Association between acquired rifamycin resistance and the pharmacokinetics of rifabutin and isoniazid among patients with HIV and tuberculosis. Clin Infect Dis 2005; 40:1481–91.
Perriens JH, St. Louis ME, Mukadi YB, et al. Pulmonary tuberculosis in HIV-infected patients in Zaire: a controlled trial of treatment for either 6 or 12 months. N Engl J Med 1995; 332:779–84.
Kitahata MM, Gange SJ, Abraham AG, et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 2009; 360: 1815–26.
Whalen C, Nsubuga P, Okwera A, et al. Impact of pulmonary tuberculosis on survival of HIV-infected adults: a prospective epidemiologic study in Uganda. AIDS 2000; 14: 1219–28.
Ledergerber B, Egger M, Erard V, et al. AIDS-related opportunistic illnesses occurring after initiation of potent antiretroviral therapy: the Swiss HIV Cohorts Study. JAMA 1999; 282: 2220–26.
