Marchenko O. H.

PREDICTION OF TUBERCULOSIS DEVELOPMENT IN HIV-INFECTED PATIENTS ON ANTIRETROVIRAL THERAPY


About the author:

Marchenko O. H.

Heading:

CLINICAL AND EXPERIMENTAL MEDICINE

Type of article:

Scentific article

Annotation:

The HIV epidemic has become global. Therefore, according to the latest data in the world, about 37 million people live with HIV. Effective antiretroviral therapy (ART) allows to prolong and improve the quality of life of HIV-infected individuals, but its prescription does not always lead to a decrease in HIV viral load and restoration of immune system function. Thus in the ART era, tuberculosis (TB) remains the major cause of hospitalization and death in patients with acquired immunodeficiency syndrome (AIDS). The search for predictors of the development of TB in patients on ART is an urgent scientific and practical task. The purpose of the study is to investigate the predictors of progression and to create a prognostic model for the development of TB in HIV-infected patients, receiving ART, based on the determination of clinical and genetic markers. A retrospective cohort study of 181 HIV-infected patients was conducted. To achieve the goal, the data of the specified cohort of 29 patients were compared with those of those who did not have signs of TB on ART – 152 persons. The univariate and multivariate logistic regression analysis was used to identify the associations between the clinical, genetic parameters and TB development in HIV-infected persons on ART with calculation of the odds ratio (OR) and its 95% confidence interval [95% CI]. P-values less than 0.05 were assumed to be statistically significant. The significance of the statistical model was evaluated using the criterion χ2, diagnostic power – by the analysis of operating characteristics of diagnostic tests (Receiver Operating Characteristic – ROC), which included determining of the sensitivity, specificity, the total number of correct predictions and constructing a ROC – curve with measuring the area under it (AUC). As a result of the analysis of 27 potential predictors of the development of TB in patients on ART, 8 significant risk factors were identified in HIV-infected patients with TB development/activation, namely: male (OR=4,38, p=0,020), injecting drug use (OR=2,72, p=0,054), initial viral load of HIV > 1.0x105 copies/ml (OR=2,25, p = 0,051), immunological failure of ART (OR=6,16, p = 0,000), low adherence to ART (OR=4,44, p = 0,004), body mass index (BMI) below18,5 kg/m2 (OR=3,10, p = 0,009), haemoglobin level below 100 g/l (OR=2,36, p = 0,037), and allele 299Gly of TLR4 gene (OR=3,35, p = 0,011). A prognostic model of 5 predictors was created, including: male gender (OR=5,02, p=0,018), initial viral load of HIV > 1.0x105 copies/ml (OR=3,92, p=0,009), immunological failure of ART (OR=9,85, p=0,000), BMI < 18.5 kg/ m2 (OR=3,51, p=0,016) and carrier of the allele 299Gly of the TLR4 gene (OR=4,07,p=0,010), statistically significant (χ²=44,64, р<0,001) with operational characteristics: sensitivity – 72,4%, specificity – 86,0% and had a high predictive efficiency (area under the ROC curve – 0,8407). Implementation the proposed prognostic model into practice will provide an opportunity to predict the probability of the TB development/activation in HIV-infected patients on ART with sufficient precision, and to individualize the tactics of managing this category of patients based on complex evaluation of simple clinical features.

Tags:

HIV-infection, development/activation of tuberculosis on ART, polymorphism, predictive model.

Bibliography:

  1. Global AIDS monitoring 2019: UNAIDS. 2019. [Internet]. 2019 [cited 28 August 2019]. Available from: http://www.unaids.org/sites/default/ files/media_asset/global-aids-monitoring_en.pdf
  2. VIL-infektsiia v Ukraini. Informatsiinyi biuleten № 48. Derzhavna ustanova «Ukrainskyi tsentr kontroliu za sotsialno nebezpechnymy khvorobamy Ministerstva okhorony zdorovia Ukrainy». № 48. 2017 r. [Internet]. 2017 [cited 28 August 2019]. Dostupno: https://phc.org.ua/uploads/ documents/c21991/1489e96901f2c3c26f4210ba6a9698cc.pdf [in Ukrainian].
  3. Cox JA, Kiggundu D, Elpert L, Meintjes G, Colebunders R, Alamo S, et al. Temporal trends in death causes in adults attending an urban HIV clinic in Uganda: a retrospective chart review. [Internet]. BMJ open. 2016 Jan 16;6(1):1-10. 2016 [cited 28 August 2019]. Available from: https:// bmjopen.bmj.com/content/bmjopen/6/1/e008718.full.pdf
  4. da Silva Escada RO, Velasque L, Ribeiro SR, Cardoso SW, Marins LMS, Grinsztejn E, et al. Mortality in patients with HIV-1 and tuberculosis coinfection in Rio de Janeiro, Brazil-associated factors and causes of death. BMC infectious diseases. 2017 May 30;17(1):373.
  5. Luo B, Sun J, Cai R, Shen Y, Liu L, Wang J, et al. Spectrum of opportunistic infections and risk factors for in-hospital mortality of admitted AIDS patients in Shanghai. Medicine. 2016 May 27;95(21):e3802.
  6. Holubovska OA, Petrenko VI, Shkurba AV, Sukach MM. Kliniko-laboratorni osoblyvosti perebihu koinfektsii tuberkulozu ta khronichnoho hepatytu S u VIL-infikovanykh khvorykh. Medychna nauka Ukrainy. 2015;11(3-4):50-5. [in Ukrainian].
  7. Van Rie A, Westreich D, Sanne I. Tuberculosis in patients receiving antiretroviral treatment: incidence, risk factors and prevention strategies. Journal of acquired immune deficiency syndromes. 2011 April;56(4):349-55.
  8. Gunda D, Maganga S, Nkandala I, Kilonzo S, Mpondo B, Shao E, et al. Prevalence and Risk Factors of Active TB among Adult HIV Patients Receiving ART in Northwestern Tanzania: A Retrospective Cohort Study. Canadian Journal of Infectious Diseases and Medical Microbiology. 2018;2018:1-7.
  9. Pathmanathan I, Dokubo E, Shiraishi R, Agolory S, Auld A, Onotu D, et al. Incidence and predictors of tuberculosis among HIV-infected adults after initiation of antiretroviral therapy in Nigeria, 2004-2012. Plos One. 2017;12(3):e0173309.
  10. Crump J, Wu X, Kendall M, Ive P, Kumwenda J, Grinsztejn B, et al. Predictors and outcomes of Mycobacterium tuberculosis bacteremia among patients with HIV and tuberculosis co-infection enrolled in the ACTG A5221 STRIDE study. BMC Infectious Diseases. 2015;15(1):12.
  11. Koval T, Dubynska G. Prohnozuvannia perebihu VIL-infektsii ta poshuk predyktoriv rozvytku SNIDu ta lehenevoho tuberkulozu. ScienceRise. Medical Science. 2017;10(18):16-9. [in Ukrainian].
  12. Klinichnyi protokol antyretrovirusnoi terapii VIL-infektsii u doroslykh ta pidlitkiv: Nakaz MOZ Ukrainy vid 12.07.2010 r. № 551 [Internet]. 2010 [cited 28 August 2019]. Dostupno: https://phc.org.ua/uploads/documents/17d68b/b5fdd660e1cf98ee0b35bd1e43fd482f.pdf [in Ukrainian].
  13. Klinichnyi protokol diahnostyky ta likuvannia oportunistychnykh infektsii i zahalnykh symptomiv u doroslykh ta pidlitkiv (Nakaz MOZ Ukrainy 13.04.2007, № 182) [Internet]. 2007 [cited 28 August 2019]. Dostupno: https://zakon.rada.gov.ua/rada/file/docs/4/d242884.doc [in Ukrainian].
  14. Crabtree-Ramírez B, Caro-Vega Y, Shepherd B, Wehbe F, Cesar C, Cortés C, et al. Cross-Sectional Analysis of Late HAART Initiation in Latin America and the Caribbean: Late Testers and Late Presenters. Plos One. 2011;6(5):e20272.

Publication of the article:

«Bulletin of problems biology and medicine» Issue 3 (152), 2019 year, 146-151 pages, index UDK 616.002.5-02:[616.98:578.828:615.281.8]-037

DOI: