Decreased All-Cause and Liver-Related Mortality Risk in HIV/Hepatitis B Virus Coinfection Coinciding With the Introduction of Tenofovir-Containing Combination Antiretroviral Therapy
van Welzen, Berend J; Smit, Colette; Boyd, Anders; Lieveld, Faydra I; Mudrikova, Tania; Reiss, Peter; Brouwer, Annemarie E; Hoepelman, Andy I M; Arends, Joop E
(2020) Open forum infectious diseases, volume 7, issue 7
(Article)
Abstract
Background: The development of efficacious combination antiretroviral therapy (cART) has led to a dramatic decrease in mortality in HIV-positive patients. Specific data on the impact in HIV/hepatitis B virus (HBV)-coinfected patients are lacking. In this study, all-cause and cause-specific mortality risks stratified per era of diagnosis are investigated. Methods: Data
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were analyzed from HIV/HBV-coinfected patients enrolled in the ATHENA cohort between January 1, 1998, and December 31, 2017. Risk for (cause-specific) mortality was calculated using Cox proportional hazard regression analysis, comparing patients diagnosed before 2003 with those diagnosed ≥2003. Risk factors for all-cause and liver-related mortality were also assessed using Cox proportional hazard regression analysis. Results: A total of 1301 HIV/HBV-coinfected patients were included (14 882 person-years of follow-up). One-hundred ninety-eight patients (15%) died during follow-up. The adjusted hazard ratio (aHR) for all-cause mortality in patients diagnosed in or after 2003 was 0.50 (95% CI, 0.35-0.72) relative to patients diagnosed before 2003. Similar risk reduction was observed for liver-related (aHR, 0.29; 95% CI, 0.11-0.75) and AIDS-related mortality (aHR, 0.44; 95% CI, 0.22-0.87). Use of a tenofovir-containing regimen was independently associated with a reduced risk of all-cause and liver-related mortality. Prior exposure to didanosine/stavudine was strongly associated with liver-related mortality. Ten percent of the population used only lamivudine as treatment for HBV. Conclusions: All-cause, liver-related, and AIDS-related mortality risk in HIV/HBV-coinfected patients has markedly decreased over the years, coinciding with the introduction of tenofovir. Tenofovir-containing regimens, in absence of major contraindications, should be strongly encouraged in this population.
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Keywords: Coinfection, Hepatitis B virus, HIV, Liver-related mortality, Tenofovir, Clinical Neurology, Oncology, Journal Article
ISSN: 2328-8957
Publisher: Oxford University Press
Note: Funding Information: Financial support. The ATHENA cohort is managed by Stichting HIV Monitoring and supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment. Potential conflicts of interest. Berend van Welzen: no conflict of interest. Colette Smit: grants from the Netherlands Ministry of Health, Welfare and Sport, National Institute for Public Health and the Environment, Centre for Infectious Disease Control during the conduct of the study. Anders Boyd: grants from ANRS and Sidaction outside the submitted work. Faydra Lieveld: no conflict of interest. Tania Mudrikova: grant from Gilead and honoraria paid to the institution for scientific advisory board participation from Viiv outside the submitted work. Peter Reiss: grants from Gilead Sciences, Merck, and ViiV Healthcare and honoraria paid to the institution for scientific advisory board participation from Gilead Sciences, ViiV Healthcare, and Merck & Teva outside the submitted work. Annemarie Brouwer: no conflict of interest. Andy Hoepelman: no conflict of interest. Joop Arends: honoraria paid to the institution for scientific advisory board participation from Gilead, MSD, and ViiV healthcare outside the submitted work. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Clinical centers. Amsterdam UMC, AMC site, Amsterdam: HIV treating physicians: M. van der Valk,* S. E. Geerlings, A. Goorhuis, J. W. Hovius, B. Lempkes, F. J. B. Nellen, T. van der Poll, J. M. Prins, P. Reiss, M. van Vugt, W. J. Wiersinga, F. W. M. N. Wit. HIV nurse consultants: M. van Duinen, J. van Eden, A. Hazenberg, A. M. H. van Hes, F. J. J. Pijnappel, S. Y. Smalhout, A. M. Weijsenfeld. HIV clinical virologists/chemists: S. Jurriaans, N. K. T. Back, H. L. Zaaijer, B. Berkhout, M. T. E. Cornelissen, C. J. Schinkel, K. C. Wolthers. Amsterdam UMC, VUmc site, Amsterdam: HIV treating physicians: E. J. G. Peters,* M. A. van Agtmael, R. S. Autar, M. Bomers, K. C. E. Sigaloff. HIV nurse consultants: M. Heitmuller, L. M. Laan. HIV clinical virologists/chemists: C. W. Ang, R. van Houdt, M. Jonges. Emma Kinderziekenhuis (Amsterdam UMC, AMC site): HIV treating physicians: T. W. Kuijpers, D. Pajkrt, H. J. Scherpbier. HIV nurse consultants: C. de Boer, A. van der Plas, A. M. Weijsenfeld. Admiraal De Ruyter Ziekenhuis, Goes: HIV treating physicians: M. van den Berge,* A. Stegeman. HIV nurse consultants: S. Baas, L. Hage de Looff. HIV clinical virologists/chemists: A. Buiting, A. Reuwer, J. Veenemans, B. Wintermans. Catharina Ziekenhuis, Eindhoven: HIV treating physicians: M. J. H. Pronk,* H. S. M. Ammerlaan. HIV nurse consultants: D. N. J. van den Bersselaar, E. S. de Munnik. HIV clinical virologists/chemists: B. Deiman, A. R. Jansz, V. Scharnhorst, J. Tjhie, M. C. A. Wegdam. DC Klinieken Lairesse—HIV Focus Centrum: HIV treating physicians: A. van Eeden,* J. Nellen, M. van der Valk. HIV nurse consultants: W. Brokking, L. J. M. Elsenburg, H. Nobel. HIV clinical virologists/chemists: C. J. Schinkel. ETZ (Elisabeth-TweeSteden Ziekenhuis), Tilburg: HIV treating physicians: M. E. E. van Kasteren,* M. A. H. Berrevoets, A. E. Brouwer. HIV nurse consultants: A. Adams, R. van Erve, B. A. F. M. de Kruijf-van de Wiel, S. Keelan-Phaf, B. van de Ven. Data collection: B. A. F. M. de Kruijf-van de Wiel, B. van der Ven. HIV clinical virologists/chemists: A. G. M. Buiting, J. L. Murck. Erasmus MC, Rotterdam: HIV treating physicians: T. E. M. S. de Vries-Sluijs,* H. I. Bax, E. C. M. van Gorp, N. C. de Jong-Peltenburg, M. de Mendonça Melo, E. van Nood, J. L. Nouwen, B. J. A. Rijnders, C. Rokx, C. A. M. Schurink, L. Slobbe, A. Verbon. HIV nurse consultants: N. Bassant, J. E. A. van Beek, M. Vriesde, L. M. van Zonneveld. Data collection: J. de Groot. HIV clinical virologists/chemists: C. A. B. Boucher, M. P. G Koopmans, J. J. A van Kampen. Erasmus MC–Sophia, Rotterdam: HIV treating physicians: P. L. A. Fraaij, A. M. C. van Rossum, C. L. Vermont. HIV nurse consultants: L. C. van der Knaap, E. Visser. Flevoziekenhuis, Almere: HIV treating physicians: J. Branger,* R. A. Douma. HIV nurse consultant: A. S. Cents-Bosma, C. J. H. M. Duijf-van de Ven. HagaZiekenhuis, Den Haag: HIV treating physicians: E. F. Schippers,* C. van Nieuwkoop. HIV nurse consultants: J. M. van IJperen, J. Geilings. Data collection: G. van der Hut. HIV clinical virologist/chemist: N. D. van Burgel. HMC (Haaglanden Medisch Centrum), Den Haag: HIV treating physicians: E. M. S. Leyten,* L. B. S. Gelinck, F. Mollema. HIV nurse consultants: S. Davids-Veldhuis, C. Tearno, G. S. Wildenbeest. HIV clinical virologists/chemists: E. Heikens. Isala, Zwolle: HIV treating physicians: P. H. P. Groeneveld,* J. W. Bouwhuis, A. J. J. Lammers. HIV nurse consultants: S. Kraan, A. G. W. van Hulzen, M. S. M. Kruiper. Data collection: G. L. van der Bliek, P. C. J. Bor. HIV clinical virologists/chemists: S. B. Debast, G. H. J. Wagenvoort. Leids Universitair Medisch Centrum, Leiden: HIV treating physicians: F. P. Kroon,* M. G. J. de Boer, H. Jolink, M. M. C. Lambregts, A. H. E. Roukens, H. Scheper. HIV nurse consultants: W. Dorama, N. van Holten. HIV clinical virologists/chemists: E. C. J. Claas, E. Wessels. Maasstad Ziekenhuis, Rotterdam: HIV treating physicians: J. G. den Hollander,* R. El Moussaoui, K. Pogany. HIV nurse consultants: C. J. Brouwer, J. V. Smit, D. Struik-Kalkman. Data collection: T. van Niekerk. HIV clinical virologists/chemists: O. Pontesilli. Maastricht UMC+, Maastricht: HIV treating physicians: S. H. Lowe,* A. M. L. Oude Lashof, D. Posthouwer, M. E. van Wolfswinkel. HIV nurse consultants: R. P. Ackens, K. Burgers, J. Schippers. Data collection: B. Weijenberg-Maes. HIV clinical virologists/chemists: I. H. M. van Loo, T. R. A. Havenith. Medisch Centrum Leeuwarden, Leeuwarden: HIV treating physicians: M. G. A. van Vonderen,* L. M. Kampschreur. HIV nurse consultants: S. Faber, R. Steeman-Bouma. HIV clinical virologists/ chemists: A. Al Moujahid. Medisch Spectrum Twente, Enschede: HIV treating physicians: G. J. Kootstra,* C. E. Delsing. HIV nurse consultants: M. van der Burg-van de Plas, L. Scheiberlich. Noordwest Ziekenhuisgroep, Alkmaar: HIV treating physicians: W. Kortmann,* G. van Twillert,* R. Renckens. HIV nurse consultant and data collection: D. Ruiter-Pronk, F. A. van Truijen-Oud. HIV clinical virologists/chemists: J. W. T. Cohen Stuart, E. R. Jansen, M. Hoogewerf, W. Rozemeijer, W. A. van der Reijden, J. C. Sinnige. OLVG, Amsterdam: HIV treating physicians: K. Brinkman,* G. E. L. van den Berk, W. L. Blok, K. D. Lettinga, M. de Regt, W. E. M. Schouten, J. E. Stalenhoef, J. Veenstra, S. M. E. Vrouenraets. HIV nurse consultants: H. Blaauw, G. F. Geerders, K. Hoeksema, M. J. Kleene, M. Kok, M. Knapen, I. B. van der Meché, E. Mulder-Seeleman, A. J. M. Toonen, S. Wijnands, E. Wttewaal. HIV clinical virologists: D. Kwa. Radboudumc, Nijmegen: HIV treating physicians: R. van Crevel,* K. van Aerde, A. S. M. Dofferhoff, S. S. V. Henriet, H. J. M. ter Hofstede, J. Hoogerwerf, M. Keuter, O. Richel. HIV nurse consultants: M. Albers, K. J. T. Grintjes-Huisman, M. de Haan, M. Marneef, R. Strik-Albers. HIV clinical virologists/chemists: J. Rahamat-Langendoen, F. F. Stelma. HIV clinical pharmacology consultant: D. Burger. Rijnstate, Arnhem: HIV treating physicians: E. H. Gisolf,* R. J. Hassing, M. Claassen. HIV nurse consultants: G. ter Beest, P. H. M. van Bentum, N. Langebeek. HIV clinical virologists/chemists: R. Tiemessen, C. M. A. Swanink. Spaarne Gasthuis, Haarlem: HIV treating physicians: S. F. L. van Lelyveld,* R. Soetekouw. HIV nurse consultants: L. M. M. van der Prijt, J. van der Swaluw. Data collection: N. Bermon. HIV clinical virologists/chemists: W. A. van der Reijden, R. Jansen, B. L. Herpers, D. Veenendaal. Medisch Centrum Jan van Goyen, Amsterdam: HIV treating physicians: D. W. M. Verhagen, F. N. Lauw. HIV nurse consultants: M. C. van Broekhuizen, M. van Wijk. Universitair Medisch Centrum Groningen, Groningen: HIV treating physicians: W. F. W. Bierman,* M. Bakker, J. Kleinnijenhuis, E. Kloeze, A. Middel, D. F. Postma, E. H. Schölvinck, Y. Stienstra, C. L. A. R. Verhage, M. Wouthuyzen-Bakker. HIV nurse consultants: A. Boonstra, H. de Groot-de Jonge, P. A. van der Meulen, D. A. de Weerd. HIV clinical virologists/chemists: H. G. M. Niesters, C. C. van Leer-Buter, M. Knoester. Universitair Medisch Centrum Utrecht, Utrecht: HIV treating physicians: A. I. M. Hoepelman,* J. E. Arends, R. E. Barth, A. H. W. Bruns, P. M. Ellerbroek, T. Mudrikova, J. J. Oosterheert, E. M. Schadd, B. J. van Welzen. HIV nurse consultants: K. Aarsman, B. M. G. Griffioen-van Santen, I. de Kroon. Data collection: M. van Berkel, C. S. A. M. van Rooijen. HIV clinical virologists/chemists: R. Schuurman, F. Verduyn-Lunel, A. M. J. Wensing. Publisher Copyright: © The Author(s) 2020.
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