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


Surial, Bernard; Chammartin, Frédérique; Damas, José; Calmy, Alexandra; Haerry, David; Stöckle, Marcel; Schmid, Patrick; Bernasconi, Enos; Fux, Christoph A; Tarr, Philip E; Günthard, Huldrych F; Wandeler, Gilles; Rauch, Andri; Swiss HIV Cohort Study (2023). Impact of Integrase Inhibitors on Cardiovascular Disease Events in People With Human Immunodeficiency Virus Starting Antiretroviral Therapy. Clinical Infectious Diseases, 77(5):729-737.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
04 Faculty of Medicine > Institute of Medical Virology
04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Microbiology (medical)
Health Sciences > Infectious Diseases
Language:English
Date:11 September 2023
Deposited On:12 Jan 2024 11:00
Last Modified:30 Jun 2024 01:37
Publisher:Oxford University Press
ISSN:1058-4838
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/cid/ciad286
PubMed ID:37157869
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)