Loveleen Bansi-Matharu1, Andrew Phillips2, Cristiana Oprea3, Katharina Grabmeier-Pfistershammer4, Huldrych F Günthard5, Stephane De Wit6, Giovanni Guaraldi7, Jorg J Vehreschild8, Ferdinand Wit9, Matthew Law10, Jan-Christian Wasmuth11, Nikoloz Chkhartishvili12, Antonella d'Arminio Monforte13, Eric Fontas14, Jan Vesterbacka15, Jose M Miro16, Antonella Castagna17, Christoph Stephan18, Josep M Llibre19, Bastian Neesgaard20, Lauren Greenberg2, Colette Smith2, Ole Kirk21, Claudine Duvivier22, Gordana Dragovic23, Jens Lundgren20, Nikos Dedes24, Andreas Knudsen25, Joel Gallant26, Vani Vannappagari27, Lars Peters20, Daniel Elbirt28, Mario Sarcletti4, Dominique L Braun5, Coca Necsoi6, Cristina Mussini7, Camilla Muccini17, Natalie Bolokadze12, Jennifer Hoy29, Amanda Mocroft30, Lene Ryom20. 1. Centre for Clinical Research, Epidemiology, Modelling and Evaluation, Institute for Global Health, University College London, London, UK. Electronic address: l.bansi-matharu@ucl.ac.uk. 2. Centre for Clinical Research, Epidemiology, Modelling and Evaluation, Institute for Global Health, University College London, London, UK. 3. Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; Victor Babes Clinical Hospital for Infectious and Tropical Diseases, Bucharest, Romania. 4. Austrian HIV Cohort Study, Department of Dermatology and Venerology, Medical University Innsbruck, Innsbruck, Austria. 5. Swiss HIV Cohort Study, University of Zurich, Zurich, Switzerland; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland. 6. CHU Saint-Pierre, Centre de Recherche en Maladies Infectieuses a.s.b.l., Brussels, Belgium. 7. Modena HIV Cohort, Università degli Studi di Modena, Modena, Italy. 8. University Hospital Cologne, Cologne, Germany. 9. AIDS Therapy Evaluation in the Netherlands cohort, HIV Monitoring Foundation, Amsterdam, Netherlands. 10. The Australian HIV Observational Database, University of New South Wales, Sydney, NSW, Australia. 11. University Hospital Bonn, Bonn, Germany. 12. Georgian National AIDS Health Information System, Infectious Diseases, AIDS and Clinical Immunology Research Center, Tbilisi, Georgia. 13. Italian Cohort Naive Antiretrovirals, ASST Santi Paolo e Carlo, Milan, Italy. 14. Nice HIV Cohort, Université Côte d'Azur et Centre Hospitalier Universitaire, Nice, France. 15. Swedish InfCare HIV Cohort, Karolinska University Hospital, Huddinge, Sweden. 16. Infectious Diseases Service. Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain. 17. San Raffaele Scientific Institute, Università Vita-Salute San Raffaele, Milan, Italy. 18. Frankfurt HIV Cohort Study, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany. 19. Department of Infectious Diseases, University Hospital Germans Trias i Pujol, Fight AIDS Foundation, Badalona, Barcelona, Spain. 20. CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 21. CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; COCOMO, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 22. AP-HP-Necker-Enfants Malades Hospital, Infectious Diseases Department, Necker-Pasteur Infectiology Center, IHU Imagine, Institut Cochin- CNRS 8104-INSERM U1016-Retrovirus, Infection and Latency Team, University of Paris, Institut Pasteur, Medical Center of Institut Pasteur, Paris, France. 23. Institute of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia. 24. European AIDS Treatment Group, Brussels, Belgium. 25. COCOMO, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 26. Gilead Sciences, Foster City, CA, USA. 27. ViiV Healthcare, Research Triangle, NC, USA. 28. Allergy, Immunology and HIV Unit, Kaplan Medical Center, Rehovot, Israel. 29. Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, VIC, Australia. 30. Centre for Clinical Research, Epidemiology, Modelling and Evaluation, Institute for Global Health, University College London, London, UK; CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Abstract
BACKGROUND: Weight gain effects of individual antiretroviral drugs are not fully understood. We investigated associations between a prespecified clinically significant increase (>7%) in body-mass index (BMI) and contemporary antiretroviral use. METHODS: The International Cohort Consortium of Infectious Diseases (RESPOND) is a prospective, multicohort collaboration, including data from 17 well established cohorts and over 29 000 people living with HIV. People with HIV under prospective follow-up from Jan 1, 2012, and older than 18 years were eligible for inclusion. Each cohort contributed a predefined minimum number of participants related to the size of the specific cohort (with a minimum of 1000 participants). Participants were required to have CD4 cell counts and HIV viral load measurement in the 12 months before or within 3 months after baseline. For all antiretroviral drugs received at or after RESPOND entry, changes from pre-antiretroviral BMI levels (baseline) were considered at each BMI measurement during antiretroviral treatment. We used logistic regression to identify individual antiretrovirals that were associated with first occurrence of a more than 7% increase in BMI from pre-antiretroviral BMI. We adjusted analyses for time on antiretrovirals, pre-antiretroviral BMI, demographics, geographical region, CD4 cell count, viral load, smoking status, and AIDS at baseline. RESULTS: 14 703 people were included in this study, of whom 7863 (53·5%) had a more than 7% increase in BMI. Compared with lamivudine, use of dolutegravir (odds ratio [OR] 1·27, 95% CI 1·17-1·38), raltegravir (1·37, 1·20-1·56), and tenofovir alafenamide (1·38, 1·22-1·35) was significantly associated with a more than 7% BMI increase, as was low pre-antiretroviral BMI (2·10, 1·91-2·31 for underweight vs healthy weight) and Black ethnicity (1·61, 1·47-1·76 vs White ethnicity). Higher CD4 count was associated with a reduced risk of BMI increase (0·97, 0·96-0·98 per 100 cells per μL increase). Relative to lamivudine, dolutegravir without tenofovir alafenamide (OR 1·21, 95% CI 1·19-1·32) and tenofovir alafenamide without dolutegravir (1·33, 1·15-1·53) remained independently associated with a more than 7% increase in BMI; the associations were higher when dolutegravir and tenofovir alafenamide were used concomitantly (1·79, 1·52-2·11, and 1·70, 1·44-2·01, respectively). INTERPRETATION: Clinicians and people with HIV should be aware of associations between weight gain and use of dolutegravir, tenofovir alafenamide, and raltegravir, particularly given the potential consequences of weight gain, such as insulin resistance, dyslipidaemia, and hypertension. FUNDING: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort and The University of Cologne HIV Cohorts, ViiV Healthcare, and Gilead Sciences.
BACKGROUND: Weight gain effects of individual antiretroviral drugs are not fully understood. We investigated associations between a prespecified clinically significant increase (>7%) in body-mass index (BMI) and contemporary antiretroviral use. METHODS: The International Cohort Consortium of Infectious Diseases (RESPOND) is a prospective, multicohort collaboration, including data from 17 well established cohorts and over 29 000 people living with HIV. People with HIV under prospective follow-up from Jan 1, 2012, and older than 18 years were eligible for inclusion. Each cohort contributed a predefined minimum number of participants related to the size of the specific cohort (with a minimum of 1000 participants). Participants were required to have CD4 cell counts and HIV viral load measurement in the 12 months before or within 3 months after baseline. For all antiretroviral drugs received at or after RESPOND entry, changes from pre-antiretroviral BMI levels (baseline) were considered at each BMI measurement during antiretroviral treatment. We used logistic regression to identify individual antiretrovirals that were associated with first occurrence of a more than 7% increase in BMI from pre-antiretroviral BMI. We adjusted analyses for time on antiretrovirals, pre-antiretroviral BMI, demographics, geographical region, CD4 cell count, viral load, smoking status, and AIDS at baseline. RESULTS: 14 703 people were included in this study, of whom 7863 (53·5%) had a more than 7% increase in BMI. Compared with lamivudine, use of dolutegravir (odds ratio [OR] 1·27, 95% CI 1·17-1·38), raltegravir (1·37, 1·20-1·56), and tenofovir alafenamide (1·38, 1·22-1·35) was significantly associated with a more than 7% BMI increase, as was low pre-antiretroviral BMI (2·10, 1·91-2·31 for underweight vs healthy weight) and Black ethnicity (1·61, 1·47-1·76 vs White ethnicity). Higher CD4 count was associated with a reduced risk of BMI increase (0·97, 0·96-0·98 per 100 cells per μL increase). Relative to lamivudine, dolutegravir without tenofovir alafenamide (OR 1·21, 95% CI 1·19-1·32) and tenofovir alafenamide without dolutegravir (1·33, 1·15-1·53) remained independently associated with a more than 7% increase in BMI; the associations were higher when dolutegravir and tenofovir alafenamide were used concomitantly (1·79, 1·52-2·11, and 1·70, 1·44-2·01, respectively). INTERPRETATION: Clinicians and people with HIV should be aware of associations between weight gain and use of dolutegravir, tenofovir alafenamide, and raltegravir, particularly given the potential consequences of weight gain, such as insulin resistance, dyslipidaemia, and hypertension. FUNDING: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort and The University of Cologne HIV Cohorts, ViiV Healthcare, and Gilead Sciences.
Authors: Myrthe L Verburgh; Ferdinand W N M Wit; Anders Boyd; Sebastiaan O Verboeket; Peter Reiss; Marc van der Valk Journal: Open Forum Infect Dis Date: 2022-06-10 Impact factor: 4.423