TOPLINE

Switching to integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) from a non-integrase inhibitor regimen was associated with a small increase in cardiovascular risk at 1 year but not at 6 years among treatment-experienced people with well-controlled HIV.

METHODOLOGY

• Researchers emulated 167 sequential target trials using data from the Swiss HIV Cohort Study included 8815 treatment-experienced adults (median age, 48 years; 69.7% were male) with HIV who had viral suppression and no prior CVD.
• A total of 539,017 person-trials were analyzed, with participants assigned to either switch to INSTI-based ART or remain on non-INSTI-based ART at each trial baseline from January 2008 through December 2019.
• Primary outcome was a composite of myocardial infarction, stroke, or invasive cardiovascular procedures, assessed over 6 years of follow-up.
• Analysis employed both intention-to-treat (ITT) and per-protocol (PP) approaches, with the PP analysis using inverse probability weighting to adjust for confounding and selection bias from treatment nonadherence.
• Median time on ART was 11 years and median CD4 cell count was 631 cells/μL.

TAKEAWAY

• During follow-up, 507 CVD events occurred in the ITT analysis, including 145 myocardial infarctions, 125 strokes, and 237 invasive cardiovascular procedures, with a median time to event of 35 months in the non-INSTI arm and 30 months in the INSTI arm.
• At 1 year, the ITT analysis showed a small early increase in CVD risk after switching to INSTI-based ART (adjusted risk ratio [aRR], 1.34; 95% CI, 1.03-1.69).
• In the ITT analysis at 6 years, the adjusted risk for CVD was 4.11% in the INSTI arm vs 3.97% in the non-INSTI arm, yielding an aRR of 1.03 (95% CI, 0.88-1.16).
• In the PP analysis at 6 years, the adjusted risk for CVD was 4.39% (95% CI: 3.54-5.00) in the INSTI arm vs 3.95% (95% CI, 3.29-4.48) in the non-INSTI arm, with an aRR of 1.11 (95% CI, 0.90-1.35).

IN PRACTICE

"Switching to an INSTI-based treatment in routine Swiss practice did not increase long-term CVD risk in people with well-controlled HIV. Although a slightly elevated absolute risk difference was observed early after switching, its magnitude was small," the authors of the study wrote .

SOURCE

The study was led by Tristan T Lee, University of Basel, Basel, Switzerland. It was published online on August 7 in Open Forum Infectious Diseases.

LIMITATIONS

The study could not fully exclude residual confounding by indication, as clinicians may have preferentially switched patients at higher baseline CVD risk to INSTI-based regimens. The analysis was restricted to a Swiss cohort with high-quality data and consolidated clinical practices, which may limit generalizability to other settings or health systems. The relatively small number of CVD events in the INSTI arm, particularly in subgroup analyses, reduced statistical power to detect modest differences.

DISCLOSURES

The study was supported by grants from the Swiss National Science Foundation, the Moritz Straus Foundation, and Swiss University Hospitals. Several authors reported receiving grants, personal fees, or research support from pharmaceutical companies including ViiV Healthcare, Gilead Sciences, Merck Sharp & Dohme, Janssen-Cilag, and others, and some are employees or shareholders of these companies. Additional author disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.