Mortality of TB-HIV Co-Infection Patients Based on CD4 Level: Meta-Analysis
Abstract
Background: Tuberculosis (TB) is the most common cause of death in patients with the Human Immunodeficiency Virus (HIV). Understanding CD4 as a predictor of mortality from TBHIV coinfection is critical to improving disease management and minimizing mortality. This study aims to examine the mortality risk of TBHIV-coinfected patients based on CD4 values.
Subjects and Method: Metaanalysis was performed according to the PRISMA flow chart and the PICO model (Population: TBHIV coinfected patients, Intervention: CD4 value <200 cells/µL, Comparison: CD4≥200 cells/µL, Outcome: mortality). The databases used are Google Scholar, PubMed, Scopus, Proquest, and Science Direct. Keywords used (coinfection OR "mixed infection") AND (HIV OR "Human Immunodeficiency Virus") AND (TB OR “tuberculosis”) AND ("CD4 count" OR "T4 lymphocyte") AND “mortality”. The inclusion criteria were full-text articles with cohort studies published in 20122022, articles in English, and multivariate analysis using the adjusted hazard ratio. Analysis was performed with Revman 5.3.
Results: 17 articles with cohort design originating from Ethiopia, Khayelitsha, Kenya, Cape Town, Uganda, Brazil, Suriname, Sao Paulo, Guinea Bissau, Myanmar, Durban, Ireland, China, and multicountry studies between Europe and Latin America totaling 24,514 research sample. A meta-analysis of 10 study cohorts concluded that CD4<200 cells/µL had a 2.00 times risk of mortality compared with CD4 values ≥200 cells/µL (aHR=2.00; 95% CI 1.44 to 2.78; p<0.001). A meta-analysis of 7 study cohorts concluded that CD4<100 cells/µL had a 2.40 time risk of mortality compared with CD4 values≥200 cells/µL (aHR=2.40; 95% CI 1.61 to 3.57; p<0.001). A meta-analysis of 7 study cohorts concluded that CD4<50 cells/µL had a 3.12 times risk of mortality compared with CD4 values≥200 cells/μL (aHR=3.12; 95% CI 1.51 to 6.46; p<0.001).
Conclusion: Decreased CD4 values increase the risk of mortality.
Keywords: tuberculosis, HIV, CD4, mortality, meta-analysis
Correspondence: Victoria Husadani Permata Sari. Master’s Program in Public Health, Universitas Sebelas Maret. Jl. Ir Sutami 36A, Surakarta 57126, Jawa Tengah. Email: victoriahusadani@gmail.com. Mobile: 081393539020.
Indonesian Journal of Medicine (2022), 07(04): 456470
https://doi.org/10.26911/theijmed.2022.07.04.11
References
Assefa A, Gelaw B, Getnet G, Yitayew G (2014). The effect of incident tuberculosis on immunological response of HIV patients on highly active antiretroviral therapy at the university of Gondar hospital, northwest Ethiopia: a retrospective follow-up study. BMC Infect Dis. (27): 14468. Doi: 10.1186/1471233414468.
Brothers TD, Kirkland S, Theou S, Zona S, Malagoli A, Wallace LM, Stentarelli C, et all., (2017). Predictors of transitions in frailty severity and mortality among people aging with HIV. PLoS One. 12(10). Doi: 10.1371/journal.pone.0185352.
de Faria Gomes NM, da Mota Bastos MC, Marins RM, Barbosa AA, Soares LC, de Oliveira Wilken de Abreu AM, Souto Filho JT (2015). Differences between Risk Factors Associated with Tuberculosis Treatment Abandonment and Mortality. Pulm Med. Doi: 10.1155/2015/546106.
Ellis P, Martin W, Dodd P (2017). CD4 count and tuberculosis risk in HIV positive adults not on ART: A systematic review and meta-analysis. PeerJ. 2017(12). Doi: 10.7717/PEERJ.4165/SUPP4.
Gandhi NR, Andrews JR, Brust JCM, Weissman D, Heo M, Moll AP, Friedland GH, Shah NS (2012). Risk factors for mortality among MDR and XDR-TB patients in a high HIV prevalence setting. IJTLD. 16(1):90–97. Doi: 10.5588/ijtld.11.0153.
Kantipong P, Murami K, Moolphate S, Aung M, Yamada N (2012). Causes of mortality among tuberculosis and HIV coinfected patients in Chiang rai, northern Thailand. HIV/AIDS Res. Palliat. Care. 4:159–168. Doi: 10.2147/HIV.S33535.
Kiros T, Dejen E, Tiruneh M, Tiruneh T, Eyayu T, Amogne K (2019). The magnitude and Associated Factors of Pulmonary Tuberculosis Among HIV/AIDS Patients Attending Antiretroviral Therapy Clinic at Debre Tabor Specialized Hospital, Northwest Ethiopia. HIV AIDS (Auckl. 12:849–58.
Kisuya J, Chemtai A, Raballah E, Okumu W, Keter A, Ouma C (2018). The role of Mycobacterium tuberculosis antigen-specific cytokines in the determination of acid-fast bacilli culture status in pulmonary tuberculosis patients coinfected with human immunodeficiency virus. Pan Afr Med J. 31:166.
Layer EH, Kennedy CE, Beckham SW, Mbwambo JK, Likindikoki S, Davis WW, Kerrigan DL, Brahmbatt H. (2014). Multilevel factors affecting entry into and engagement in the HIV continuum of care in Iringa, Tanzania. PloS one. 9(8). Doi: 10.1371/JOURNAL.PONE.0104961.
Mitku AA, Dessie ZG, Muluneh EK, Workie DL (2016). Prevalence and associated factors of TB/HIV coinfection among HIV Infected patients in Amhara region, Ethiopia. Afr Health Sci. 16(2):588–95.
Moola S, Munn Z, Tufanaru C, Aromataris E, Sears K, Sfetcu R, Currie M, Quereshi M, Mattis P, Lisy K, Mu P (2017). Checklist for Cohort Studies. Joanna Briggs Institute Reviewer’s Manual; pp. 1–7. Available at: https://joannabriggs.org/ebp/critical_appraisal_tools
Muyaya LM, Musanda EM, Tamuzi JL (2019). Human immunodeficiency virus-associated tuberculosis care in Botswana: evidence from a real-world setting. BMC Infect Dis. 19(1):767.
Naidoo K, Baxter C, Abdool Karim SS (2013). When to start antiretroviral therapy during tuberculosis treatment. Curr Opin Infect Dis. 26(1):35–42.
Nansera D, Bajunirwe F, Elyanu P, Asiimwe C, Amanyire G, Graziano FM (2012). Mortality and loss to follow-up among tuberculosis and HIV coinfected patients in rural southwestern Uganda. IJTLD. 16(10):1371–1376. Doi: 10.5588/ijtld.11.0589.
Odume B, Pathmanathan I, Pals S, Dokubo K, Onotu D, Obinna O, Anand D, Okpokoro E, Dutt S, Ekong E, Chukwurah N, Dakum P, Tomlinson H (2017). Delay in the Provision of Antiretroviral Therapy to HIVinfected TB Patients in Nigeria. UJPH. 5(5): 248–255. Doi: 10.13189/ujph.2017.050507.
Peetluk LS, Rebeiro PF, Ridolfi FM, Andrade BB, CordeiroSantos M, Kritski A (2022). A Clinical Prediction Model for Unsuccessful Pulmonary Tuberculosis Treatment Outcomes. Clin Infect Dis an Off Publ Infect Dis Soc Am. 74(6):973–82.
Pullar ND, Steinum H, Bruun JN, DyrholRiise AM (2014). HIV patients with latent tuberculosis living in a low endemic country do not develop active disease during a 2-year follow-up; a Norwegian prospective multicenter study. BMC Infect Dis. 14:667.
Tancredi MV, Sakabe S, Waldman EA (2022). Mortality and survival of tuberculosis coinfected patients living with AIDS in São Paulo, Brazil: a 12year cohort study. BMC infectious diseases. 22(1):223. Doi: 10.1186/s12879022072326.
Thapa S, Shrestha U (2022). Immune Reconstitution Inflammatory Syndrome. StatPearls [Internet]. 2022 May 10 [cited 2022 Aug 22]; Available from: https://www.ncbi.nlm.nih.gov/books/NBK567803/
Tweya H, BenSmith A, Kalulu M, Jahn A, Ng’ambi W, Mkandawire E, Gabriel L, Phiri S (2014). Timing of antiretroviral therapy and regimen for HIV-infected patients with tuberculosis: the effect of revised HIV guidelines in Malawi. BMC Public Health. 14:183.
Wejse C, Patsche CB, Kühle A, Bamba FJV, Mendes MS, Lemvik G, Gomes V, Rudolf F (2015). Impact of HIV1, HIV2, and HIV1+2 dual infection on the outcome of tuberculosis. Int J Infect Dis. 32:128–34.
Wondimu W, Dube L, Kabeta T (2020). Factors affecting survival rates among adult TB/HIV coinfected patients in Mizan tepi university teaching hospital, southwest Ethiopia. HIV/AIDS Res Palliat Care [Internet]. 12:157–64. Available from: https://www.scopus.com/inward/record.uri?eid=2s2.085083824518&doi=10.2147%2FHIV.S242756&partnerID=40&md5=65ffba40e565a522254e2b6f2bd3d07e
World Health Organization (2021). Global Tuberculosis Report 2021. 1–57.
YendeZuma N, Naidoo K (2016). The Effect of Timing of Initiation of Antiretroviral Therapy on Loss to Followup in HIV Tuberculosis Coinfected Patients in South Africa: An OpenLabel, Randomized, Controlled Trial. J Acquir Immune Defic Syndr. 72(4):430–6.
Yuengling KA, Padayatchi N, Wolf A, Mathema B, Brown T, Horsburgh R, O’Donnell M (2018). Effect of Antiretroviral Therapy on Treatment Outcomes in a Prospective Study of Extensively drug-resistant Tuberculosis (XDR-TB) HIV Coinfection Treatment in KwaZulu-Natal, South Africa. J. Acquir. Immune Defic. Syndr. 79(4): 474–480. Doi: 10.1097/QAI. 0000000000001833.
