Background:
Integrase strand transfer inhibitors (INSTI) have become essential components of antiretroviral therapy (ART). A recent study suggests that INSTI-based ART may lead to an increased risk for cardiovascular (CVD) events in the first two years compared to other ART combinations. However, analyzing treatment-naïve and treatment-experienced individuals together may have introduced bias. We estimated the impact of starting INSTI-based compared to other ART on cardiovascular events among treatment-naïve people with HIV (PWH) by emulating a target trial to minimize the risk of bias.
Methods:
We included participants from the Swiss HIV Cohort Study who were treatment-naïve after May 2008, when the first INSTI became available in Switzerland. Baseline was defined as the date of the first treatment start (INSTI vs. other ART), and individuals were followed until the first CVD event (myocardial infarction, stroke, or intervention on arteries), loss to follow-up, death, or last cohort visit. Individuals who stopped the initial strategy (INSTI or other ART) were censored at that time. We estimated cardiovascular disease risk differences using pooled logistic regression with inverse probability of treatment and censoring weights, taking into account time-fixed and time-varying confounders (covariates listed in figure legend).
Results:
Of 5287 treatment-naïve individuals, 2032 (38.4%) started INSTI-based ART, and 3255 (61.6%) started other ART combinations. Individuals who started INSTI were less likely to be women (16% vs. 26%), less likely to be of African origin (12% vs. 19%), and had a higher median CD4 nadir (346 vs. 281 cells/µL) compared to individuals starting other ART. Smoking status, history of cardiovascular disease, and use of antiplatelet agents were similar in both groups, but INSTI-starters were more likely to receive abacavir (26% vs. 11%). Within 25’567 person-years (PY), 113 CVD events occurred (incidence rate 4.42 per 1000 PY, 95% CI 3.68–5.31). Unadjusted incidence rates were 6.49 per 1000 PY (4.99–8.46) among INSTI starters and 3.39 per 1000 PY (2.62–4.39) among those who started other ART (Panel A). In adjusted analyses, risk differences between INSTI and other ART starters were -0.02% (-0.32% to 0.21%) after 1 year, -0.17% (-0.65% to 0.10%) after 2 years, and -0.38% (-1.29 to 0.52) after 5 years (Panel B).
Conclusions:
In this target trial emulation, we found no evidence of a difference in CVD event risk with starting INSTI-based compared to other ART in treatment-naïve PWH.
Cardiovascular dosease events in people living with HIV starting ART