Impact of integrase inhibitors on cardiovascular disease events in people with human immunodeficiency virus starting antiretroviral therapy. Clinical Infectious Diseases
Surial et al. performed a target trial emulation to examine the effect of starting integrase inhibitor (INSTI) based antiretroviral therapy (ART) compared to other ART combinations on cardiovascular disease (CVD) events among treatment-naïve participants in the Swiss HIV Cohort Study (SHCS).
The target trial framework is a method for designing an observational data analysis that specifies treatment eligibility, the intervention, patient follow-up and clinical outcomes similar to a randomized trial. This approach provides a clear alignment of time-zero, and reduces the potential for selection and immortal time bias. The authors included all SHCS participants who were HIV treatment-naïve after the first INSTI became available in Switzerland (May 2008) and subsequently initiated ART. Individuals were classified as INSTI starters if they received any INSTI-containing ART as their first treatment, and as other ART starters if they received other ART combinations. Time zero was defined as the date of first ART start, and the outcome of interest was the first CVD event, which included myocardial infarction, stroke, and invasive cardiovascular procedure.
Between May 2008 and September 2022, 1’837 (34.3%) individuals started INSTI-based ART, and 3’525 (65.7%) started other ART combinations. Compared to people with HIV who started other ART combinations, those who started INSTI were less likely to be women, less likely to be of African origin, more likely to have an eGFR <60 mL at start, and to receive abacavir and tenofovir alafenamide. Within a median follow-up of 4.9 years, 116 CVD events occurred. Adjusted risk differences for CVD events between individuals who initiated INSTI and those who initiated other ART were as follows: -0.08% (95% CI, −0.20 to 0.19) at 6 months, -0.17% (−0.37 to 0.19) at 1 year, -0.61% (−0.72 to 0.09) at 2 years, and -0.71% (−2.16 to 0.94) at 8 years.
In summary, this study found no difference in the risk of developing CVD events between individuals who started INSTI-based ART and those who started other ART combinations. These findings contrast with the results from a large study from the RESPOND cohort collaboration, which reported a markedly increased risk for CVD events within the first two years of exposure. The accompanying editorial from the French epidemiologist Dr. Dominique Costagliola provides an excellent discussion of the methodological differences between the two studies. Further target trial emulations including treatment-experienced individuals are needed to evaluate the impact of switching to INSTI-based ART on CVD events.