Impact of Integrase Inhibitors on Cardiovascular Disease Events in People With Human Immunodeficiency Virus Starting Antiretroviral Therapy.

Background: Integrase strand transfer inhibitors (INSTIs) have been associated with an increased risk for cardiovascular disease (CVD) events. We investigated the impact of starting INSTI-based antiretroviral therapy (ART) on CVD events among treatment-naïve people with human immunodeficiency virus using a target trial framework, which reduces the potential for confounding and selection bias.
Methods: We included Swiss HIV Cohort Study participants who were ART-naïve after May 2008, when INSTIs became available in Switzerland. Individuals were categorized according to their first ART regimen (INSTI vs other ART) and were followed from ART start until the first of CVD event (myocardial infarction, stroke, or invasive cardiovascular procedure), loss to follow-up, death, or last cohort visit. We calculated hazard ratios and risk differences using pooled logistic regression models with inverse probability of treatment and censoring weights.
Results: Of 5362 participants (median age 38 years, 21% women, 15% of African origin), 1837 (34.3%) started INSTI-based ART, and 3525 (65.7%) started other ART. Within 4.9 years (interquartile range, 2.4-7.4), 116 CVD events occurred. Starting INSTI-based ART was not associated with an increased risk for CVD events (adjusted hazard ratio, 0.80; 95% confidence interval [CI], .46-1.39). Adjusted risk differences between individuals who started INSTIs and those who started other ART were -0.17% (95% CI, -.37 to .19) after 1 year, -0.61% (-1.54 to 0.22) after 5 years, and -0.71% (-2.16 to 0.94) after 8 years.
Conclusions: In this target trial emulation, we found no difference in short- or long-term risk for CVD events between treatment-naïve people with human immunodeficiency virus who started INSTI-based ART and those on other ART.
Competing Interests: Potential conflicts of interest . B. S. reports financial support to his institution for travel grants from Gilead Sciences and ViiV healthcare, and for advisory boards from Gilead Sciences. D. H.’s institution receives unrestricted educational grants from AbbVie, Gilead, MSD, and ViiV Healthcare, AstraZeneca, Roche, Pfizer, and GSK. D. H. has received advisory fees from Gilead and ViiV Healthcare and reports consulting fees from AstraZeneca and UCB, all outside the submitted work. D. H. also reports roles on PFMD Executive Committee, Gilde Healthcare Impact Council, EUPATI Advisory committee (chair), Positive Council (chair), and Aids-Hilfe Bern. M. S. reports support to his institution for advisory boards from Gilead, MSD, ViiV, Pfizer, and Moderna, as well as for travel grants from Gilead. P. S. reports financial support to his institution for advisory boards and travel grants from Gilead Sciences and ViiV Healthcare. E. B. reports financial support to his institution for advisory boards and/or travel grants from MSD, Gilead Sciences, ViiV Healthcare, Pfizer, Ely Lilly, AstraZeneca and Moderna. E. B. also reports grants or contracts paid to institution from Merck Sharp & Dohme. All remuneration went to his home institution and not to E. B. personally, and all remuneration was provided outside the submitted work. P. E. T.’s institution reports unrestricted and educational grants from Gilead, ViiV, and MSD, and advisory fees from Gilead and ViiV, and reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from MSD, ViiV, and Gilead, all outside the submitted work. H. F. G. has received unrestricted research grants from Gilead Sciences; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, Merck, Johnson and Johnson, Janssen, GSK, Novartis, and ViiV Healthcare; a travel grant from Gilead and grants from the Swiss National Science Foundation, Swiss HIV Cohort Study, Swiss HIV Cohort Research Foundation, the Yvonne Jacob Foundation, and from National Institutes of Health. G. W. reports unrestricted research grants from Gilead Sciences and Roche Diagnostics, as well as travel grants and advisory board/lecture fees from ViiV, Gilead Sciences, and MSD, all paid to his institution. A. R. reports support to his institution for advisory boards and/or travel grants from MSD, Gilead Sciences, and Pfizer, and an investigator-initiated trial (IIT) grant from Gilead Sciences. A. R. also reports participation on a Data Safety Monitoring Board or Advisory Board for Moderna. All remuneration went to his home institution and not to A. R. personally, and all remuneration was provided outside the submitted work. C. A. F. reports a Gilead grant for clinical and laboratory follow-up of drug substitution patients regarding HCV in our area, paid to the Department of Infectious Diseases of the Kantonsspital Aarau, Switzerland; support for Advisory Board attendance for Gilead, Menarini, Moderna, MSD, and ViiV, paid to institution. A. C. reports unrestricted educational grants from MSD, Gilead, and ViiV. All other authors report no potential conflicts. 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.
(© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)