Current German/Austrian antiretroviral treatment guidelines recommend more than 20 combination regimens for first-line therapy, without a preference. Regimens include two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an integrase strand transfer inhibitor (INSTI), a non-NRTI (NNRTI) or a boosted protease inhibitor (PI). The objective was to examine the outcomes of recommended first-line ART in Germany.
This nationwide observational study included treatment-naïve chronically HIV-1 infected patients receiving one of the recommended first-line regimens. Patients were allocated to three arms (INSTI, NNRTI, PI) and were prospectively followed for 24 months. Delayed treatment initiation was defined by a baseline CD4 T-cell count of < 350/µl or CDC clinical stage C.
Among a total of 434 patients enrolled, virologic failure was rare and occurred in 4.3% (6/141) in the PI arm, in 3.3% (4/122) in the NNRTI arm and in 0.6% (1/171) in the INSTI arm (p = 0.10). De novo drug resistance mutations developed in only two patients in the NNRTI arm. Nonetheless, treatment modifications were frequent (51%) and mostly performed for strategic reasons. Retention on all initial compounds at month 24 was 64%, 49%, and 22% in the INSTI, NNRTI and PI arms respectively. Delayed treatment initiation was common (47%) and more frequently observed in patients in the PI arm. It was not associated with virological failure.
High efficacy and low virological failure rates were observed with recommended first-line regimens independent of delayed treatment initiation, chosen regimen and subsequent treatment modifications, demonstrating the validity of the current treatment guidelines.
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We thank Nikola Hanhoff from dagnae e.V., Berlin, and Birgit Mück from MUC Research for study coordination and monitoring, Paul Lauscher from MUC Research, Munich, for statistical analyses. We thank all participating patients as well as the staff and investigators of the PROPHET study group: Practice Kreuzberg, Hubert Schulbin, Berlin; Center for Infectiology Berlin Prenzlauer Berg GmbH (Zibp), Axel Baumgarten, Christoph Mayr, Berlin; MVZ Aerzteforum Seestrasse, Wolfgang Schmidt, Berlin; Department of Medicine I, Bonn University Hospital, Jürgen Rockstroh, Bonn; Praxis Ebertplatz, Christoph Wyen, Esther Voigt, Tim Kümmerle, Cologne; Practice Hohenstaufenring, Stefan Scholten, Stephan Schneeweiss, Cologne; Department I of Internal Medicine, University Hospital of Cologne, Gerd Fätkenheuer, Cologne; Center for HIV and Hepatogastroenterology, Stefan Mauss, Düsseldorf; University HIV/STD Center, Essen, Department of Dermatology and Venerology, University Hospital Essen, Stefan Esser, Essen; Infektiologikum Frankfurt, Markus Bickel, Stephan Klauke, Thomas Lutz; Infektiologikum Freiburg Susanne Usadel; Practice Dr. Frank Ackermann, Halle; ifi-Studien und Projekte GmbH an der Asklepios Klinik St. Georg, Haus L, Albrecht Stoehr, Andreas Plettenberg, Hamburg; ICH Studycenter, Christian Hoffmann, Hans-Jürgen Stellbrink, Michael Sabranski, Carl Knud Schewe, Hamburg; Hannover Medical School, Matthias Stoll, Hannover; Center for Medical Studies, Hans Heiken, Hannover; MVZ Karlsplatz, HIV Research and Clinical Care Centre, Munich, Hans Jäger, Munich; Practice Isartor, Ramona Pauli, Werner Becker, Munich; University Hospital of Munich, Johannes Bogner, Munich; Technical University of Munich, School of Medicine, Christoph D. Spinner, Munich; prinzmed, Practice for infectious diseases, Nils Postel, Munich; Center for Interdisciplinary Medicine, Stefan Christensen, Muenster; Practice Schwabstrasse 26, Markus Mueller, Albrecht Ulmer, Stuttgart; Institute for Health Care Management and Research, Jürgen Wasem, Anja Neumann, Duisburg-Essen.
We thank Janssen-Cilag for providing the financial support for the conduct of study.
Conflict of interest
Markus Bickel has received honoraria for lecturing from the Hess.Arbeitsgemeinschaft der HIV-Versorger (HIVAG), travelling grants from Deutsche Arbeitsgemeinschaft niedergelassener Ärzte in der Versorgung HIV-Infizierter e. V. (dagnä) and has received research grants from AbbVie, Janssen-Cilag, MSD, Gilead Sciences, Glaxo Smith Kline, dagnä, Deutsche Leberstiftung, Institut für HIV Forschung Universitätsklinikum Essen, Infektionsmedizinisches Zentrum Hamburg (ICH). Christian Hoffmann has received honoraria for lecturing, advisory boards and/or travelling grants from AbbVie, EusaPharm, Gilead Sciences, HEXAL, Hormosan, Janssen-Cilag, MSD and ViiV Healthcare; he has also received research grants from AbbVie, Janssen-Cilag, MSD and Gilead Sciences. Stephan Klauke has received travelling grants from Deutsche Arbeitsgemeinschaft niedergelassener Ärzte in der Versorgung HIV-Infizierter e. V. (dagnä) and has received research grants from AbbVie, Janssen-Cilag, MSD, Gilead Sciences, Glaxo Smith Kline, dagnä, Deutsche Leberstiftung, Institut für HIV Forschung Universitätsklinikum Essen, Infektionsmedizinisches Zentrum Hamburg (ICH). Christoph D. Spinner has received grants for travel and participation in advisory boards or speaker’s honoraria from AbbVie, Astellas, Bristol-Meyers Squibb, Gilead, Janssen-Cilag, MSD, and ViiV Healthcare. He has also received grants for investigator-sponsored studies from Gilead Sciences, Janssen-Cilag, and ViiV Healthcare. Eva Wolf has received grants for travel and participation in advisory boards or speaker’s honoraria from AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Janssen-Cilag, MSD Sharp & Dohme, Roche, and ViiV Healthcare. Knud Schewe has received speakers honoraria as well as honoraria for advisory boards and/or travel grants from AbbVie, Gilead Sciences, HEXAL, Janssen-Cilag, MSD and ViiV Healthcare as well as travel grants and conference sponsoring from Deutsche Arbeitsgemeinschaft niedergelassener Ärzte in der Versorgung HIV-Infizierter e. V. (dagnä). Axel Baumgarten has received honoraria for lecturing, advisory boards and/or travelling grants from AbbVie, Gilead Sciences, Janssen, Sanofi, MSD and ViiV Healthcare. Stefan Esser has received honoraria for lecturing, advisory boards and/or travelling grants from AbbVie, Gilead Sciences, HEXAL, Janssen-Cilag, MSD and ViiV Healthcare; he has also received research grants from ViiV, Janssen-Cilag, MSD and Gilead Sciences. Christoph Wyen has received grants for travel and participation in advisory boards or speaker’s honoraria from AbbVie, Bristol-Meyers Squibb, Gilead, Janssen-Cilag, MSD, and ViiV Healthcare. On behalf of all other authors, the corresponding author states that there is no conflict of interest.
The primary ethical approval was received by the University Duisburg/Essen on June 25, 2014 (ID 14-5847-BO), the study was registered at the Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, ID7237), the National Association of Statutory Health Insurance Funds (GKV Spitzenverband, ID40128) and the German clinical trial registry (Deutsche Register Klinischer Studien, ID 00006321).
Consent to participate
Partcipating centers signed a contract for the conduction of the study with the Deutsche Arbeitsgemeinschaft niedergelassener Ärzte in der Versorgung HIV-Infizierter e. V. (dagnä) e. V. located in Berlin.
Consent for publication
All co-authors have read the manuscript had sufficient time to consider changes and finally agreed to its publication in the present form.
Availability of data and material
The data of the study were presented and discussed at all investigator meetings which were held twice yearly over the entire time the study was conducted in conjunction with two national HIV meetings.
Statistical analysis was conducted using Stata/SE 15.1 (StataCorp LLC, Texas, USA).
The members of the investigators of the PROPHET study group are listed in acknowledgements.
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Bickel, M., Hoffmann, C., Wolf, E. et al. High effectiveness of recommended first-line antiretroviral therapies in Germany: a nationwide, prospective cohort study. Infection 48, 453–461 (2020). https://doi.org/10.1007/s15010-020-01428-1