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Observational Study
. 2015 Dec 30;10(12):e0145380.
doi: 10.1371/journal.pone.0145380. eCollection 2015.

Major Challenges in Clinical Management of TB/HIV Coinfected Patients in Eastern Europe Compared with Western Europe and Latin America

Anne Marie W Efsen  1 , Anna Schultze  2 , Frank A Post  3 , Alexander Panteleev  4 , Hansjakob Furrer  5 , Robert F Miller  6 , Marcelo H Losso  7 , Javier Toibaro  7 , Aliaksandr Skrahin  8 , Jose M Miro  9 , Joan A Caylà  10 , Enrico Girardi  11 , Mathias Bruyand  12 , Niels Obel  13 , Daria N Podlekareva  1 , Jens D Lundgren  1 , Amanda Mocroft  2 , Ole Kirk  1 ; TB:HIV study group in EuroCoord
Affiliations
Observational Study

Major Challenges in Clinical Management of TB/HIV Coinfected Patients in Eastern Europe Compared with Western Europe and Latin America

Anne Marie W Efsen et al. PLoS One. .

Abstract

Objectives: Rates of TB/HIV coinfection and multi-drug resistant (MDR)-TB are increasing in Eastern Europe (EE). We aimed to study clinical characteristics, factors associated with MDR-TB and predicted activity of empiric anti-TB treatment at time of TB diagnosis among TB/HIV coinfected patients in EE, Western Europe (WE) and Latin America (LA).

Design and methods: Between January 1, 2011, and December 31, 2013, 1413 TB/HIV patients (62 clinics in 19 countries in EE, WE, Southern Europe (SE), and LA) were enrolled.

Results: Significant differences were observed between EE (N = 844), WE (N = 152), SE (N = 164), and LA (N = 253) in the proportion of patients with a definite TB diagnosis (47%, 71%, 72% and 40%, p<0.0001), MDR-TB (40%, 5%, 3% and 15%, p<0.0001), and use of combination antiretroviral therapy (cART) (17%, 40%, 44% and 35%, p<0.0001). Injecting drug use (adjusted OR (aOR) = 2.03 (95% CI 1.00-4.09), prior anti-TB treatment (3.42 (1.88-6.22)), and living in EE (7.19 (3.28-15.78)) were associated with MDR-TB. Among 585 patients with drug susceptibility test (DST) results, the empiric (i.e. without knowledge of the DST results) anti-TB treatment included ≥3 active drugs in 66% of participants in EE compared with 90-96% in other regions (p<0.0001).

Conclusions: In EE, TB/HIV patients were less likely to receive a definite TB diagnosis, more likely to house MDR-TB and commonly received empiric anti-TB treatment with reduced activity. Improved management of TB/HIV patients in EE requires better access to TB diagnostics including DSTs, empiric anti-TB therapy directed at both susceptible and MDR-TB, and more widespread use of cART.

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Conflict of interest statement

Competing Interests: AMW reports a personal grant from University Hospital Copenhagen. AS reports grants and travel support from University College London. HF reports consultancy fees from ViiV, Gilead, Abbvie, MSD, Jannsen, BMS and grants from ViiV, Gilead, AbbVie, Roche, Boehringer, MSD, BMS, Janssen outside the submitted work. RM reports payment for lectures from ViiV, Merck, Gilead and Janssen outside the submitted work. JMM reports consultancy fees from Abbvie, Novartis, payment for lectures from Abbvie, Bristol-Myers Squibb, Gilead Sciences, Merck and Novartis y ViiV Healthcare and grants from Cubist, Gilead, ViiV Healthcare, Novartis, Merck, Fondo de Investigaciones Sanitarias - Instituto de Salud Carlos III, Fundación para la Investigación y Prevención del Sida en España, Ministerio de Sanidad, Servicios Sociales e Igualdad, National Institutes of Health and NEAT outside the submitted work. EG reports board membership for Janssen-Cilag, consultancy fees from Abbot-Diagnostics, payment for lectures from BMS, ViiV Healthcare, Jannsen and grants from Gilead Sciences outside the submitted work. JT reports grants from EuroCoord and University of Buenos Aires, CICAL during conduct of the study. MHL reports grants from EuroCoord, employment from University of Buenos Aires, Hospital JM Ramos Mejia, CICAL and grants from NIH, University of Minnesota, University of New South Wales, travel fees from Gador outside the submitted work. AM reports speaker fees, travel fees and honorarium from BI, Gilead, Pfizer, Merck and BMS outside the submitted work. OK reports board membership from Gilead, Merck, ViiV, consultancy fees from Gilead, payment for lectures from Abbott, Gilead, Tibotec, travel fees from Abbott, BMS, Gilead, Merck, ViiV and grants from Bristol-Myers Squibb, Janssen, Merck, Pfizer, GlaxoSmithKline outside the submitted work. For the remaining authors, none were declared. Although several authors have received grants, honoraria or travel support from a number of pharmaceutical companies, none have declared a conflict of interest in relation to the work presented in this manuscript. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Factors associated with MDR-TB in multivariable logistic regression analysis.
Fig 2
Fig 2. Proportion (95% CI) receiving RHZ-based empiric therapy (a) and proportion (95%CI) with MDR-TB (b) in different countries and study regions.
The intraregional differences in the use of RHZ-based empiric anti-TB treatment are shown in relation to the observed MDR-TB prevalence.
Fig 3
Fig 3. Susceptibility of empiric anti-TB treatment (a)1 and hypothetical susceptibility presuming RHZE had been initiated (b)2.
1The number of active drugs for a patient was calculated based on initial anti-TB therapy and DST results within the first month of therapy (available for 585/1396 patients). 2The number of active drugs in the initial anti-TB treatment regimen, assuming RHZE had been initiated in all subjects (available for 585/1396 patients).
See this image and copyright information in PMC

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