Haidong Lu1, Stephen R Cole1, Daniel Westreich1, Michael G Hudgens2, Adaora A Adimora1,3, Keri N Althoff4, Michael J Silverberg5, Kate Buchacz6, Jun Li6, Jessie K Edwards1, Peter F Rebeiro7, Viviane D Lima8, Vincent C Marconi9,10, Timothy R Sterling7, Michael A Horberg11, M John Gill12, Mari M Kitahata13, Joseph J Eron1,3, Richard D Moore14. 1. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 2. Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 3. Division of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 4. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA. 5. Division of Research, Kaiser Permanente Northern California, Oakland, California, USA. 6. Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. 7. Vanderbilt University Medical Center, Nashville, Tennessee, USA. 8. Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. 9. Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA. 10. Department of Global Health, Emory University Rollins School of Public Health, Atlanta, Georgia, USA. 11. Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville, Maryland, USA. 12. Department of Medicine, University of Calgary, Calgary, Alberta, Canada. 13. Department of Medicine, University of Washington, Seattle, Washington, USA. 14. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Abstract
BACKGROUND: Integrase strand transfer inhibitor (InSTI)-based regimens are now recommended as first-line antiretroviral therapy (ART) for adults with human immunodeficiency virus, but evidence on long-term clinical effectiveness of InSTI-based regimens remains limited. We examined whether InSTI-based regimens improved longer-term clinical outcomes. METHODS: We included participants from clinical cohorts in the North American AIDS Cohort Collaboration on Research and Design who initiated their first ART regimen, containing either InSTI (ie, raltegravir, dolutegravir, and elvitegravir-cobicistat) or efavirenz (EFV) as an active comparator, between 2009 and 2016. We estimated observational analogs of 6-year intention-to-treat and per-protocol risks, risk differences (RDs), and hazard ratios (HRs) for the composite outcome of AIDS, acute myocardial infarction, stroke, end-stage renal disease, end-stage liver disease, or death. RESULTS: Of 15 993 participants, 5824 (36%) initiated an InSTI-based and 10 169 (64%) initiated an EFV-based regimen. During the 6-year follow-up, 440 in the InSTI group and 1097 in the EFV group incurred the composite outcome. The estimated 6-year intention-to-treat risks were 14.6% and 14.3% for the InSTI and EFV groups, respectively, corresponding to a RD of 0.3% (95% confidence interval, -2.7% to 3.3%) and a HR of 1.08 (.97-1.19); the estimated 6-year per-protocol risks were 12.2% for the InSTI group and 11.9% for the EFV group, corresponding to a RD of 0.3% (-3.0% to 3.7%) and a HR of 1.09 (.96-1.25). CONCLUSIONS: InSTI- and EFV-based initial ART regimens had similar 6-year composite clinical outcomes. The risk of adverse clinical outcomes remains substantial even when initiating modern ART.
BACKGROUND: Integrase strand transfer inhibitor (InSTI)-based regimens are now recommended as first-line antiretroviral therapy (ART) for adults with human immunodeficiency virus, but evidence on long-term clinical effectiveness of InSTI-based regimens remains limited. We examined whether InSTI-based regimens improved longer-term clinical outcomes. METHODS: We included participants from clinical cohorts in the North American AIDS Cohort Collaboration on Research and Design who initiated their first ART regimen, containing either InSTI (ie, raltegravir, dolutegravir, and elvitegravir-cobicistat) or efavirenz (EFV) as an active comparator, between 2009 and 2016. We estimated observational analogs of 6-year intention-to-treat and per-protocol risks, risk differences (RDs), and hazard ratios (HRs) for the composite outcome of AIDS, acute myocardial infarction, stroke, end-stage renal disease, end-stage liver disease, or death. RESULTS: Of 15 993 participants, 5824 (36%) initiated an InSTI-based and 10 169 (64%) initiated an EFV-based regimen. During the 6-year follow-up, 440 in the InSTI group and 1097 in the EFV group incurred the composite outcome. The estimated 6-year intention-to-treat risks were 14.6% and 14.3% for the InSTI and EFV groups, respectively, corresponding to a RD of 0.3% (95% confidence interval, -2.7% to 3.3%) and a HR of 1.08 (.97-1.19); the estimated 6-year per-protocol risks were 12.2% for the InSTI group and 11.9% for the EFV group, corresponding to a RD of 0.3% (-3.0% to 3.7%) and a HR of 1.09 (.96-1.25). CONCLUSIONS: InSTI- and EFV-based initial ART regimens had similar 6-year composite clinical outcomes. The risk of adverse clinical outcomes remains substantial even when initiating modern ART.
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