Integrase strand-transfer inhibitor use and cardiovascular events in adults with HIV: an emulation of target trials in the HIV-CAUSAL Collaboration and the Antiretroviral Therapy Cohort Collaboration. Lancet HIV
Rein et al. on behalf of the Antiretroviral Therapy Cohort Collaboration and the HIV-CAUSAL Collaboration aimed to examine the effect of initiation of integrase strand-transfer inhibitors (INSTI) regimens on the risk of cardiovascular events by emulating target trials separately in individuals who had never previously used antiretroviral therapy (ART) (ART-naive) and in individuals with previous use of non-INSTI-based ART (ART experienced).
They used routinely recorded clinical data from 12 cohorts that collected information on cardiovascular events, BMI, and blood pressure from two international consortia of cohorts of people with HIV from Europe and North America. The study estimated the standardised 4-year risks of cardiovascular events (myocardial infarction, stroke, or invasive cardiovascular procedure) via pooled logistic regression models adjusting for time and baseline covariates.
The analysis in ART-naive individuals included 10’767 INSTI initiators and 8’292 non-initiators of INSTI. There were 43 cardiovascular events in INSTI initiators (median follow-up of 29 months; IQR 15–45) and 52 in non-initiators (39 months; 18–47): standardised 4-year risks were 0·76% (95% CI 0·51 to 1·04) in INSTI initiators and 0·75% (0·54 to 0·98) in non-INSTI initiators; risk ratio 1·01 (0·57 to 1·57); risk difference 0·0089% (–0·43 to 0·36). The analysis in ART-experienced individuals included 7’875 INSTI initiators and 373’965 non-initiators. There were 56 events in INSTI initiators (median follow-up 18 months; IQR 9–29) and 3103 events (808 unique) in non-INSTI initiators (26 months; 15–37) in non-initiators: standardised 4-year risks 1·41% (95% CI 0·88 to 2·03) in INSTI initiators and 1·48% (1·28 to 1·71) in non-initiators; risk ratio 0·95 (0·60 to 1·36); risk difference –0·068% (–0·60 to 0·52).
In conclusion the study suggest that initiation of INSTI does not substantially increase cardiovascular risk across 4 years with 4-year risk ratios centred around 1 and risk differences centred around 0 in both ART-naive and ART-experienced individuals. The upper limit of the 95% CI for the risk difference corresponds to an absolute increase in 4-year risk in INSTI initiators of only 0·36% in ART-naive individuals and 0·52% in ART-experienced individuals, which is unlikely to be a clinically meaningful difference. Overall, the risk of cardiovascular events was higher in ART-experienced compared with ART-naive individuals, which would be expected due to the ART-experienced population being older and havening higher prevalence of cardiovascular risk factors.