Long-term mortality after tuberculosis treatment among persons living with HIV in Haiti

Yvetot Joseph, Zhiwen Yao, Akanksha Dua, Patrice Severe, Sean E Collins, Heejung Bang, Marc Antoine Jean-Juste, Oksana Ocheretina, Alexandra Apollon, Margaret L McNairy, Kathryn Dupnik, Etienne Cremieux, Anthony Byrne, Jean W Pape, Serena P Koenig, Yvetot Joseph, Zhiwen Yao, Akanksha Dua, Patrice Severe, Sean E Collins, Heejung Bang, Marc Antoine Jean-Juste, Oksana Ocheretina, Alexandra Apollon, Margaret L McNairy, Kathryn Dupnik, Etienne Cremieux, Anthony Byrne, Jean W Pape, Serena P Koenig

Abstract

Introduction: Long-term mortality among TB survivors appears to be higher than control populations without TB in many settings. However, data are limited among persons with HIV (PWH). We assessed the association between cured TB and long-term mortality among persons with PWH in Haiti.

Methods: A prospective cohort of PWH from the CIPRA HT-001 trial was followed from study enrolment (August 2005 to July 2008) to study closure (December 2018) to compare mortality between participants with and without TB. The index date for the survival analysis was defined as 240 days after TB diagnosis or randomization date. Time to death was described using Kaplan-Meier curves, and log-rank tests were used to compare time to death between the TB and no-TB cohorts. The association between TB and long-term mortality was estimated with multivariable Cox models.

Results: Of the 816 participants in the CIPRA HT-001 trial, 77 were excluded for a history of TB prior to study enrolment and 31 were excluded due to death or attrition prior to the index date, leaving 574 in the no-TB and 134 in the TB cohort. Twenty-four (17.9%) participants in the TB and 48 (8.4%) in the no-TB cohort died during follow-up. Five and 10-year mortality rates were 14.2% and 17.9% respectively, in the TB cohort, and 6.1% and 8.4% in the no-TB cohort. In Kaplan-Meier analysis, participants in the TB cohort had a significantly shorter time to death (log-rank p < 0.001). In multivariable analysis, TB treatment was the only predictor of mortality (HR: 2.78; 95% CI: 1.61, 4.79). Sensitivity analyses, which included only baseline TB cases, an index date of two years after TB diagnosis, and study enrolment and case-control matching yielded results that were consistent with primary analyses.

Conclusions: PWH who are successfully treated for TB have higher long-term mortality than those who are never diagnosed with TB, even after accounting for acute TB-related mortality. A better understanding of the underlying mechanisms associated with TB sequelae is critically needed to guide specific interventions. Until then, more aggressive measures for health promotion and disease prevention are essential to improve long-term survival for PWH after TB treatment.

Trial registration: ClinicalTrials.gov NCT00120510.

Keywords: AIDS; HIV; long-term mortality; opportunistic infections; tuberculosis.

© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.

Figures

Figure 1
Figure 1
CIPRA HT‐001 original study design and observational follow‐up.
Figure 2
Figure 2
Study population for current analysis.
Figure 3
Figure 3
Time from CIPRA HT‐001 enrollment to TB diagnosis for patients with incident TB.
Figure 4
Figure 4
Kaplan–Meier estimates of survival in the TB and No‐TB cohorts (starting from 240 days after TB diagnosis or randomization date).

References

    1. Global Tuberculosis Report . Geneva: World Health Organization; 2020.; 2020. [cited 2020 Dec 30]. Available from:
    1. Global HIV and AIDS statistics — 2020 fact sheet. UNAIDS. [cited 2020 Sep 25]. Available from:
    1. Fox GJ, Nguyen VN, Dinh NS, Nghiem LPH, Le TNA, Nguyen TA, et al. Post‐treatment mortality among patients with tuberculosis: a prospective cohort study of 10 964 patients in Vietnam. Clin Infect Dis. 2019;68(8):1359–66.
    1. Hoger S, Lykens K, Beavers SF, Katz D, Miller TL. Longevity loss among cured tuberculosis patients and the potential value of prevention. Int J Tuberc Lung Dis. 2014;18(11):1347–52.
    1. Shuldiner J, Leventhal A, Chemtob D, Mor Z. Mortality after anti‐tuberculosis treatment completion: results of long‐term follow‐up. Int J Tuberc Lung Dis. 2016;20(1):43–8.
    1. Christensen AS, Roed C, Andersen PH, Andersen AB, Obel N. Long‐term mortality in patients with pulmonary and extrapulmonary tuberculosis: a Danish nationwide cohort study. Clin Epidemiol. 2014;6:405–21.
    1. Miller TL, Wilson FA, Pang JW, Beavers S, Hoger S, Sharnprapai S, et al. Mortality hazard and survival after tuberculosis treatment. Am J Public Health. 2015;105(5):930–7.
    1. Tocque K, Convrey RP, Bellis MA, Beeching NJ, Davies PD. Elevated mortality following diagnosis with a treatable disease: tuberculosis. Int J Tuberc Lung Dis. 2005;9(7):797–802.
    1. Blondal K, Rahu K, Altraja A, Viiklepp P, Rahu M. Overall and cause‐specific mortality among patients with tuberculosis and multidrug‐resistant tuberculosis. Int J Tuberc Lung Dis. 2013;17(7):961–8.
    1. Romanowski K, Baumann B, Basham CA, Ahmad Khan F, Fox GJ, Johnston JC. Long‐term all‐cause mortality in people treated for tuberculosis: a systematic review and meta‐analysis. Lancet Infect Dis. 2019;19(10):1129–37.
    1. Koenig SP, Kim A, Shepherd BE, Cesar C, Veloso V, Cortes CP, et al. Increased mortality after tuberculosis treatment completion in persons living with human immunodeficiency virus in Latin America. Clin Infect Dis. 2020;71(1):215–7.
    1. Severe P, Juste MA, Ambroise A, Eliacin L, Marchand C, Apollon S, et al. Early versus standard antiretroviral therapy for HIV‐infected adults in Haiti. N Engl J Med. 2010;363(3):257–65.
    1. Collins SE, Jean Juste MA, Koenig SP, Secours R, Ocheretina O, Bernard D, et al. CD4 deficit and tuberculosis risk persist with delayed antiretroviral therapy: 5‐year data from CIPRA HT‐001. Int J Tuberc Lung Dis. 2015;19(1):50–7.
    1. Blumberg HM, Burman WJ, Chaisson RE, Daley CL, Etkind SC, Friedman LN, et al. American thoracic society/centers for disease control and prevention/infectious diseases society of America: treatment of tuberculosis. Am J Respir Crit Care Med. 2003;167(4):603–62.
    1. Ministère de la Santè Publique et de la population (MSPP) . Programme National de Lutte contre la Tuberculose (PNLT): Manuel de Normes de la Tuberculose en Haiti. Port‐au‐Prince, Haiti: MSPP; 2013.
    1. Fitzgerald DW, Desvarieux M, Severe P, Joseph P, Johnson WD Jr, Pape JW. Effect of post‐treatment isoniazid on prevention of recurrent tuberculosis in HIV‐1‐infected individuals: a randomised trial. Lancet. 2000;356(9240):1470–4.
    1. Hermans SM, Zinyakatira N, Caldwell J, Cobelens FGJ, Boulle A, Wood R. High rates of recurrent TB disease: a population‐level cohort study. Clin Infect Dis. 2020.
    1. Marx FM, Dunbar R, Enarson DA, Williams BG, Warren RM, van der Spuy GD, et al. The temporal dynamics of relapse and reinfection tuberculosis after successful treatment: a retrospective cohort study. Clin Infect Dis. 2014;58(12):1676–83.
    1. Basu S, Maru D, Poolman E, Galvani A. Primary and secondary tuberculosis preventive treatment in HIV clinics: simulating alternative strategies. Int J Tuberc Lung Dis. 2009;13(5):652–8.
    1. Pasipanodya JG, Miller TL, Vecino M, Munguia G, Garmon R, Bae S, et al. Pulmonary impairment after tuberculosis. Chest. 2007;131(6):1817–24.
    1. Menezes AM, Hallal PC, Perez‐Padilla R, Jardim JR, Muino A, Lopez MV, et al. Tuberculosis and airflow obstruction: evidence from the PLATINO study in Latin America. Eur Respir J. 2007;30(6):1180–5.
    1. Byrne AL, Marais BJ, Mitnick CD, Lecca L, Marks GB. Tuberculosis and chronic respiratory disease: a systematic review. Int J Infect Dis. 2015;32:138–46.
    1. Crothers K, Butt AA, Gibert CL, Rodriguez‐Barradas MC, Crystal S, Justice AC, et al. Increased COPD among HIV‐positive compared to HIV‐negative veterans. Chest. 2006;130(5):1326–33.
    1. Akanbi MO, Taiwo BO, Achenbach CJ, Ozoh OB, Obaseki DO, Sule H, et al. HIV associated chronic obstructive pulmonary disease in Nigeria. J AIDS Clin Res. 2015;6(5):1000453.
    1. Pefura‐Yone EW, Fodjeu G, Kengne AP, Roche N, Kuaban C. Prevalence and determinants of chronic obstructive pulmonary disease in HIV infected patients in an African country with low level of tobacco smoking. Respir Med. 2015;109(2):247–54.
    1. Garcia Garrido HM, Mak AMR, Wit F, Wong GWM, Knol MJ, Vollaard A, et al. Incidence and risk factors for invasive pneumococcal disease and community‐acquired pneumonia in human immunodeficiency virus‐infected individuals in a high‐income setting. Clin Infect Dis. 2020;71(1):41–50.
    1. Kirwan PD, Amin‐Chowdhury Z, Croxford SE, Sheppard C, Fry N, Delpech VC, et al. Invasive pneumococcal disease in people with human immunodeficiency virus in England, 1999–2017. Clin Infect Dis. 2020.
    1. Collini PJ, Bewley MA, Mohasin M, Marriott HM, Miller RF, Geretti AM, et al. HIV gp120 in the lungs of antiretroviral therapy‐treated individuals impairs alveolar macrophage responses to pneumococci. Am J Respir Crit Care Med. 2018;197(12):1604–15.
    1. Summary of WHO Position Papers ‐ Recommendations for Routine Immunization. Updated April 2019. [cited 2020 Aug11]. Available from:
    1. Guidelines for Managing Advanced HIV Disease and Rapid Initiation of Antiretroviral Therapy. World Health Organization, 2017. [cited 2019 Sep 1, 2019]. Available from:
    1. French N, Nakiyingi J, Carpenter LM, Lugada E, Watera C, Moi K, et al. 23‐valent pneumococcal polysaccharide vaccine in HIV‐1‐infected Ugandan adults: double‐blind, randomised and placebo controlled trial. Lancet. 2000;355(9221):2106–11.
    1. French N, Gordon SB, Mwalukomo T, White SA, Mwafulirwa G, Longwe H, et al. A trial of a 7‐valent pneumococcal conjugate vaccine in HIV‐infected adults. N Engl J Med. 2010;362(9):812–22.
    1. Watera C, Nakiyingi J, Miiro G, Muwonge R, Whitworth JA, Gilks CF, et al. 23‐Valent pneumococcal polysaccharide vaccine in HIV‐infected Ugandan adults: 6‐year follow‐up of a clinical trial cohort. AIDS. 2004;18(8):1210–3.
    1. US Department of Health and Human Services . Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Figure: Recommended Immunization Schedule for Adults and Adolescents with HIV Infection. [cited 2020 Aug 1]. Available from:
    1. Lonnroth K, Jaramillo E, Williams BG, Dye C, Raviglione M. Drivers of tuberculosis epidemics: the role of risk factors and social determinants. Soc Sci Med. 2009;68(12):2240–6.
    1. Pettit AC, Giganti MJ, Ingle SM, May MT, Shepherd BE, Gill MJ, et al. Increased non‐AIDS mortality among persons with AIDS‐defining events after antiretroviral therapy initiation. J Int AIDS Soc. 2018;21:25031.
    1. Nou E, Lo J, Grinspoon SK. Inflammation, immune activation, and cardiovascular disease in HIV. AIDS. 2016;30(10):1495–509.
    1. Huaman MA, Kryscio RJ, Fichtenbaum CJ, Henson D, Salt E, Sterling TR, et al. Tuberculosis and risk of acute myocardial infarction: a propensity score‐matched analysis. Epidemiol Infect. 2017;145(7):1363–7.
    1. Chung WS, Lin CL, Hung CT, Chu YH, Sung FC, Kao CH, et al. Tuberculosis increases the subsequent risk of acute coronary syndrome: a nationwide population‐based cohort study. Int J Tuberc Lung Dis. 2014;18(1):79–83.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa