The mechanism(s) beyond traditional risk factors driving the increased atherosclerotic cardiovascular disease (ASCVD) risk among people with HIV (PWH) are unclear. In the general population, incident ASCVD events are associated with impaired macrophage HDL cholesterol efflux capacity (CEC), a derangement previously reported among PWH. We hypothesized that impaired CEC is associated with incident ASCVD events among PWH receiving ART. Additionally, we evaluated whether impaired CEC contributes to the differential ASCVD event rates reported for certain ARVs.
We selected participants from the AIDS Clinical Trials Group (ACTG) Longitudinally Linked Randomized Trials (ALLRT) cohort with samples available after 48 weeks of ART who experienced an ASCVD event (acute myocardial infarction or stroke) and matched them 5:1 in a case-cohort study design with participants who remained free of ASCVD. We measured macrophage-specific CEC to apolipoprotein B-depleted plasma from cases and controls at week 48 following ART initiation and evaluated the association of CEC with incident ASCVD event, controlling for ASCVD risk factors Finally, we compared CEC in participants randomized to ATV vs. Darunavir (DRV), Efavirenz (EFV) or Raltegravir (RAL), and to ABC vs. Tenofovir (TDF).
We included 1024 participants (114 cases and 910 randomly selected controls); Mean age 41 y, 80% Male, 47% Black, 29% current smokers, mean SBP 121, mean total cholesterol 191, mean BMI 27, viral suppression was 90% at week 48. In a fully adjusted model that included traditional risk factors, HDL cholesterol , and virologic suppression status at week 48, hazard ratio for ASCVD per 1 SD increase in CEC was 0.86 (95% CI: 0.70 – 1.06). CEC was not higher in participants who had achieved virologic suppression (VL<50 copies/mL; n=817): p=0.19. ATV was associated with a higher CEC when compared to other ‘third’ drugs (DRV, EFV or RAL). There was a trend toward lower CEC with ABC compared to TDF. Table 1 summarizes the models.
Unlike data from the general population, we did not observe an inverse association of CEC with risk of ASCVD among HIV-infected participants on ART. ATV use was associated with less impaired CEC than DRV, EFV and RAL, but not with lower risk of incident ASCVD events. There was a trend for lower CEC with ABC vs. TDF exposure. Larger studies will be required to fully evaluate whether certain ARVs alter CEC and its role in ASCVD progression.