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Published in: BMC Infectious Diseases 1/2018

Open Access 01-12-2018 | Research article

Differences in response to antiretroviral therapy in HIV-positive patients being treated for tuberculosis in Eastern Europe, Western Europe and Latin America

Authors: Yanink Caro-Vega, Anna Schultze, Anne Marie W. Efsen, Frank A. Post, Alexander Panteleev, Aliaksandr Skrahin, Jose M. Miro, Enrico Girardi, Daria N. Podlekareva, Jens D. Lundgren, Juan Sierra-Madero, Javier Toibaro, Jaime Andrade-Villanueva, Simona Tetradov, Jan Fehr, Joan Caylà, Marcelo H. Losso, Robert F. Miller, Amanda Mocroft, Ole Kirk, Brenda Crabtree-Ramírez

Published in: BMC Infectious Diseases | Issue 1/2018

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Abstract

Background

Efavirenz-based antiretroviral therapy (ART) regimens are preferred for treatment of adult HIV-positive patients co-infected with tuberculosis (HIV/TB). Few studies have compared outcomes among HIV/TB patients treated with efavirenz or non-efavirenz containing regimens.

Methods

HIV-positive patients aged ≥16 years with a diagnosis of tuberculosis recruited to the TB:HIV study between Jan 1, 2011, and Dec 31, 2013 in 19 countries in Eastern Europe (EE), Western Europe (WE), and Latin America (LA) who received ART concomitantly with TB treatment were included. Patients either received efavirenz-containing ART starting between 15 days prior to, during, or within 90 days after starting tuberculosis treatment, (efavirenz group), or other ART regimens (non-efavirenz group). Patients who started ART more than 90 days after initiation of TB treatment, or who experienced ART interruption of more than 15 days during TB treatment were excluded. We describe rates and factors associated with death, virological suppression, and loss to follow up at 12 months using univariate, multivariate Cox, and marginal structural models to compare the two groups of patients.

Results

Of 965 patients (647 receiving efavirenz-containing ART, and 318 a non-efavirenz regimen) 50% were from EE, 28% from WE, and 22% from LA. Among those not receiving efavirenz-containing ART, regimens mainly contained a ritonavir-boosted protease inhibitor (57%), or raltegravir (22%). At 12 months 1.4% of patients in WE had died, compared to 20% in EE: rates of virological suppression ranged from 21% in EE to 61% in WE. After adjusting for potential confounders, rates of death (adjusted Hazard Ratio; aHR, 95%CI: 1.13, 0.72–1.78), virological suppression (aHR, 95%CI: 0.97, 0.76–1.22), and loss to follow up (aHR, 95%CI: 1.17, 0.81–1.67), were similar in patients treated with efavirenz and non-efavirenz containing ART regimens.

Conclusion

In this large, prospective cohort, the response to ART varied significantly across geographical regions, whereas the ART regimen (efavirenz or non-efavirenz containing) did not impact on the proportion of patients who were virologically-suppressed, lost to follow up or dead at 12 months.
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Literature
1.
go back to reference WHO. Global tuberculosis report. World Health Organization, 2014. WHO. Global tuberculosis report. World Health Organization, 2014.
2.
go back to reference Podlekareva DN, Mocroft A, Post FA, Riekstina V, Miro JM, Furrer H, et al. Mortality from HIV and TB coinfections is higher in Eastern Europe than in Western Europe and Argentina. AIDS. 2009;23(18):2485–95.CrossRefPubMed Podlekareva DN, Mocroft A, Post FA, Riekstina V, Miro JM, Furrer H, et al. Mortality from HIV and TB coinfections is higher in Eastern Europe than in Western Europe and Argentina. AIDS. 2009;23(18):2485–95.CrossRefPubMed
3.
go back to reference Podlekareva DN, Efsen AM, Schultze A, Post FA, Skrahina AM, Panteleev A, et al. Tuberculosis-related mortality in people living with HIV in Europe and Latin America: an international cohort study. Lancet HIV. 2016;3(3):e120–31.CrossRefPubMed Podlekareva DN, Efsen AM, Schultze A, Post FA, Skrahina AM, Panteleev A, et al. Tuberculosis-related mortality in people living with HIV in Europe and Latin America: an international cohort study. Lancet HIV. 2016;3(3):e120–31.CrossRefPubMed
4.
go back to reference Mukadi YD, Maher D, Harries A. Tuberculosis case fatality rates in high HIV prevalence populations in sub-Saharan Africa. AIDS. 2001;15(2):143–52.CrossRefPubMed Mukadi YD, Maher D, Harries A. Tuberculosis case fatality rates in high HIV prevalence populations in sub-Saharan Africa. AIDS. 2001;15(2):143–52.CrossRefPubMed
5.
go back to reference Zhou J, Elliott J, Li PC, Lim PL, Kiertiburanakul S, Kumarasamy N, et al. Risk and prognostic significance of tuberculosis in patients from the TREAT Asia HIV observational database. BMC Infect Dis. 2009;9:46.CrossRefPubMedPubMedCentral Zhou J, Elliott J, Li PC, Lim PL, Kiertiburanakul S, Kumarasamy N, et al. Risk and prognostic significance of tuberculosis in patients from the TREAT Asia HIV observational database. BMC Infect Dis. 2009;9:46.CrossRefPubMedPubMedCentral
6.
go back to reference Gupta RK, Lucas SB, Fielding KL, Lawn SD. Prevalence of tuberculosis in post-mortem studies of HIV-infected adults and children in resource-limited settings: a systematic review and meta-analysis. AIDS. 2015;29(15):1987–2002.CrossRefPubMedPubMedCentral Gupta RK, Lucas SB, Fielding KL, Lawn SD. Prevalence of tuberculosis in post-mortem studies of HIV-infected adults and children in resource-limited settings: a systematic review and meta-analysis. AIDS. 2015;29(15):1987–2002.CrossRefPubMedPubMedCentral
7.
go back to reference Balcha TT, Skogmar S, Sturegard E, Bjorkman P, Winqvist N. Outcome of tuberculosis treatment in HIV-positive adults diagnosed through active versus passive case-finding. Glob Health Action. 2015;8:27048.CrossRefPubMed Balcha TT, Skogmar S, Sturegard E, Bjorkman P, Winqvist N. Outcome of tuberculosis treatment in HIV-positive adults diagnosed through active versus passive case-finding. Glob Health Action. 2015;8:27048.CrossRefPubMed
9.
go back to reference Havlir DV, Kendall MA, Ive P, Kumwenda J, Swindells S, Qasba SS, et al. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med. 2011;365(16):1482–91.CrossRefPubMedPubMedCentral Havlir DV, Kendall MA, Ive P, Kumwenda J, Swindells S, Qasba SS, et al. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med. 2011;365(16):1482–91.CrossRefPubMedPubMedCentral
10.
go back to reference Blanc FX, 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;365(16):1471–81.CrossRefPubMedPubMedCentral Blanc FX, 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;365(16):1471–81.CrossRefPubMedPubMedCentral
11.
go back to reference Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray AL, et al. Integration of antiretroviral therapy with tuberculosis treatment. N Engl J Med. 2011;365(16):1492–501.CrossRefPubMedPubMedCentral Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray AL, et al. Integration of antiretroviral therapy with tuberculosis treatment. N Engl J Med. 2011;365(16):1492–501.CrossRefPubMedPubMedCentral
12.
go back to reference Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray A, et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med. 2010;362(8):697–706.CrossRefPubMedPubMedCentral Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray A, et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med. 2010;362(8):697–706.CrossRefPubMedPubMedCentral
13.
go back to reference Schwander S, Rusch-Gerdes S, Mateega A, Lutalo T, Tugume S, Kityo C, et al. A pilot study of antituberculosis combinations comparing rifabutin with rifampicin in the treatment of HIV-1 associated tuberculosis. A single-blind randomized evaluation in Ugandan patients with HIV-1 infection and pulmonary tuberculosis. Tuber Lung Dis. 1995;76(3):210–8.CrossRefPubMed Schwander S, Rusch-Gerdes S, Mateega A, Lutalo T, Tugume S, Kityo C, et al. A pilot study of antituberculosis combinations comparing rifabutin with rifampicin in the treatment of HIV-1 associated tuberculosis. A single-blind randomized evaluation in Ugandan patients with HIV-1 infection and pulmonary tuberculosis. Tuber Lung Dis. 1995;76(3):210–8.CrossRefPubMed
14.
go back to reference Chien JY, Chien ST, Huang SY, Yu CJ. Safety of rifabutin replacing rifampicin in the treatment of tuberculosis: a single-Centre retrospective cohort study. J Antimicrob Chemother. 2014;69(3):790–6.CrossRefPubMed Chien JY, Chien ST, Huang SY, Yu CJ. Safety of rifabutin replacing rifampicin in the treatment of tuberculosis: a single-Centre retrospective cohort study. J Antimicrob Chemother. 2014;69(3):790–6.CrossRefPubMed
15.
go back to reference Rawson TM, Brima N, Almajid F, Pozniak AL, Janmohamed A, Mandalia S, et al. Outcomes from treating tuberculosis with rifampicin or rifabutin in HIV-infected persons also receiving antiretroviral therapy. J Acquir Immune Defic Syndr. 2015;68(5):e84–7.CrossRefPubMed Rawson TM, Brima N, Almajid F, Pozniak AL, Janmohamed A, Mandalia S, et al. Outcomes from treating tuberculosis with rifampicin or rifabutin in HIV-infected persons also receiving antiretroviral therapy. J Acquir Immune Defic Syndr. 2015;68(5):e84–7.CrossRefPubMed
16.
go back to reference WHO. Priority research questions for tuberculosis/human immunodeficiency virus (TB/HIV) in HIV-prevalent and resource-limited settings. Geneva: World Health Organization; 2010. WHO. Priority research questions for tuberculosis/human immunodeficiency virus (TB/HIV) in HIV-prevalent and resource-limited settings. Geneva: World Health Organization; 2010.
17.
go back to reference WHO. Tuberculosis care with TB-HIV co-management : integrated Management of Adolescent and Adult Illness (IMAI). 2007. WHO. Tuberculosis care with TB-HIV co-management : integrated Management of Adolescent and Adult Illness (IMAI). 2007.
18.
go back to reference WHO. Guidelines for national programmes and other stakeholders. 2012. WHO. Guidelines for national programmes and other stakeholders. 2012.
19.
go back to reference Migliori GB, Zellweger JP, Abubakar I, Ibraim E, Caminero JA, De Vries G, et al. European union standards for tuberculosis care. Eur Respir J. 2012;39(4):807–19. Migliori GB, Zellweger JP, Abubakar I, Ibraim E, Caminero JA, De Vries G, et al. European union standards for tuberculosis care. Eur Respir J. 2012;39(4):807–19.
23.
go back to reference Avila D, Althoff KN, Mugglin C, Wools-Kaloustian K, Koller M, Dabis F, et al. Immunodeficiency at the start of combination antiretroviral therapy in low-, middle-, and high-income countries. J Acquir Immune Defic Syndr. 2014;65(1):e8–16.PubMed Avila D, Althoff KN, Mugglin C, Wools-Kaloustian K, Koller M, Dabis F, et al. Immunodeficiency at the start of combination antiretroviral therapy in low-, middle-, and high-income countries. J Acquir Immune Defic Syndr. 2014;65(1):e8–16.PubMed
24.
go back to reference Crabtree-Ramirez B, Caro-Vega Y, Shepherd BE, Wehbe F, Cesar C, Cortes 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.CrossRefPubMedPubMedCentral Crabtree-Ramirez B, Caro-Vega Y, Shepherd BE, Wehbe F, Cesar C, Cortes 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.CrossRefPubMedPubMedCentral
26.
go back to reference Boulle A, Van Cutsem G, Cohen K, Hilderbrand K, Mathee S, Abrahams M, et al. Outcomes of nevirapine- and efavirenz-based antiretroviral therapy when coadministered with rifampicin-based antitubercular therapy. JAMA. 2008;300(5):530–9.CrossRefPubMed Boulle A, Van Cutsem G, Cohen K, Hilderbrand K, Mathee S, Abrahams M, et al. Outcomes of nevirapine- and efavirenz-based antiretroviral therapy when coadministered with rifampicin-based antitubercular therapy. JAMA. 2008;300(5):530–9.CrossRefPubMed
27.
go back to reference Murphy RA, Marconi VC, Gandhi RT, Kuritzkes DR, Sunpath H. Coadministration of lopinavir/ritonavir and rifampicin in HIV and tuberculosis co-infected adults in South Africa. PLoS One. 2012;7(9):e44793.CrossRefPubMedPubMedCentral Murphy RA, Marconi VC, Gandhi RT, Kuritzkes DR, Sunpath H. Coadministration of lopinavir/ritonavir and rifampicin in HIV and tuberculosis co-infected adults in South Africa. PLoS One. 2012;7(9):e44793.CrossRefPubMedPubMedCentral
28.
go back to reference Maartens G, Decloedt E, Cohen K. Effectiveness and safety of antiretrovirals with rifampicin: crucial issues for high-burden countries. Antivir Ther. 2009;14(8):1039–43.CrossRefPubMed Maartens G, Decloedt E, Cohen K. Effectiveness and safety of antiretrovirals with rifampicin: crucial issues for high-burden countries. Antivir Ther. 2009;14(8):1039–43.CrossRefPubMed
29.
go back to reference Minchella PA, Armitage AE, Darboe B, Jallow MW, Drakesmith H, Jaye A, et al. Elevated hepcidin at HIV diagnosis is associated with incident tuberculosis in a retrospective cohort study. Int J Tuberc Lung Dis. 2014;18(11):1337–9.CrossRefPubMed Minchella PA, Armitage AE, Darboe B, Jallow MW, Drakesmith H, Jaye A, et al. Elevated hepcidin at HIV diagnosis is associated with incident tuberculosis in a retrospective cohort study. Int J Tuberc Lung Dis. 2014;18(11):1337–9.CrossRefPubMed
30.
go back to reference Grinsztejn B, De Castro N, Arnold V, Veloso VG, Morgado M, Pilotto JH, et al. Raltegravir for the treatment of patients co-infected with HIV and tuberculosis (ANRS 12 180 reflate TB): a multicentre, phase 2, non-comparative, open-label, randomised trial. Lancet Infect Dis. 2014;14(6):459–67.CrossRefPubMed Grinsztejn B, De Castro N, Arnold V, Veloso VG, Morgado M, Pilotto JH, et al. Raltegravir for the treatment of patients co-infected with HIV and tuberculosis (ANRS 12 180 reflate TB): a multicentre, phase 2, non-comparative, open-label, randomised trial. Lancet Infect Dis. 2014;14(6):459–67.CrossRefPubMed
32.
go back to reference Howe CJ, Cole SR, Westreich DJ, Greenland S, Napravnik S, Eron JJ Jr. Splines for trend analysis and continuous confounder control. Epidemiology. 2011;22(6):874–5.CrossRefPubMedPubMedCentral Howe CJ, Cole SR, Westreich DJ, Greenland S, Napravnik S, Eron JJ Jr. Splines for trend analysis and continuous confounder control. Epidemiology. 2011;22(6):874–5.CrossRefPubMedPubMedCentral
33.
go back to reference Cain LE, Robins JM, Lanoy E, Logan R, Costagliola D, Hernan MA. When to start treatment? A systematic approach to the comparison of dynamic regimes using observational data. Int J Biostat. 2010;6(2):Article 18.CrossRefPubMed Cain LE, Robins JM, Lanoy E, Logan R, Costagliola D, Hernan MA. When to start treatment? A systematic approach to the comparison of dynamic regimes using observational data. Int J Biostat. 2010;6(2):Article 18.CrossRefPubMed
34.
go back to reference TB: HIV Study writing Group. One-year mortality of HIV-positive patients treated for rifampicin- and isoniazidsusceptible tuberculosis in Eastern Europe, Western Europe, and Latin America. AIDS. 2017;31(3):375–84. TB: HIV Study writing Group. One-year mortality of HIV-positive patients treated for rifampicin- and isoniazidsusceptible tuberculosis in Eastern Europe, Western Europe, and Latin America. AIDS. 2017;31(3):375–84.
35.
go back to reference Efsen AM, Schultze A, Post FA, Panteleev A, Furrer H, Miller RF, et al. Major challenges in clinical management of TB/HIV Coinfected patients in Eastern Europe compared with Western Europe and Latin America. PLoS One. 2015;10(12):e0145380.CrossRefPubMedPubMedCentral Efsen AM, Schultze A, Post FA, Panteleev A, Furrer H, Miller RF, et al. Major challenges in clinical management of TB/HIV Coinfected patients in Eastern Europe compared with Western Europe and Latin America. PLoS One. 2015;10(12):e0145380.CrossRefPubMedPubMedCentral
36.
go back to reference Bassett IV, Chetty S, Wang B, Mazibuko M, Giddy J, Lu Z, et al. Loss to follow-up and mortality among HIV-infected people co-infected with TB at ART initiation in Durban, South Africa. J Acquir Immune Defic Syndr. 2012;59(1):25–30.CrossRefPubMedPubMedCentral Bassett IV, Chetty S, Wang B, Mazibuko M, Giddy J, Lu Z, et al. Loss to follow-up and mortality among HIV-infected people co-infected with TB at ART initiation in Durban, South Africa. J Acquir Immune Defic Syndr. 2012;59(1):25–30.CrossRefPubMedPubMedCentral
37.
go back to reference Crabtree-Ramirez B, Caro-Vega Y, Shepherd BE, Grinsztejn B, Wolff M, Cortes CP, et al. Time to HAART initiation after diagnosis and treatment of opportunistic infections in patients with AIDS in Latin America. PLoS One. 2016;11(6):e0153921.CrossRefPubMedPubMedCentral Crabtree-Ramirez B, Caro-Vega Y, Shepherd BE, Grinsztejn B, Wolff M, Cortes CP, et al. Time to HAART initiation after diagnosis and treatment of opportunistic infections in patients with AIDS in Latin America. PLoS One. 2016;11(6):e0153921.CrossRefPubMedPubMedCentral
Metadata
Title
Differences in response to antiretroviral therapy in HIV-positive patients being treated for tuberculosis in Eastern Europe, Western Europe and Latin America
Authors
Yanink Caro-Vega
Anna Schultze
Anne Marie W. Efsen
Frank A. Post
Alexander Panteleev
Aliaksandr Skrahin
Jose M. Miro
Enrico Girardi
Daria N. Podlekareva
Jens D. Lundgren
Juan Sierra-Madero
Javier Toibaro
Jaime Andrade-Villanueva
Simona Tetradov
Jan Fehr
Joan Caylà
Marcelo H. Losso
Robert F. Miller
Amanda Mocroft
Ole Kirk
Brenda Crabtree-Ramírez
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2018
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-018-3077-x

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