Pleiotropic effects of statins include improvement of endothelial dysfunction, increased nitric oxide, antioxidant and anti-inflammatory properties, and stabilization of atherosclerotic plaques. Statins are also active against HIV-1 in vitro; however, they have never been shown to have an antiviral effect in clinical studies. Given their short half-lives, a modest virologic effect of statins is difficult to prove during cART and may require the analysis of continuous exposure. We hypothesized that continuous use of statins would increase the durability of successful cART.
We examined the time to virologic rebound after reaching an undetectable viral load (VL) in all HIV infected US-veterans who started successful cART 1995-2011, had a VL >1000 copies/mL before, and had ≥1 follow up VL within 13 months of reaching undetectability. We defined virologic failure (VF) as any VL >1,000 copies/mL or the first of 2 consecutive VL >200 copies/mL. To address bias by indication and control for adherence, we used pharmacy refill data to build a time-updated drug exposure model for cART, statins, and other cardiovascular drugs (CVMs). We determined ever use, current use, and 30-day use rate [percentage of days covered (PDC)] We used both multiply adjusted and inverse-probability-weighted (IPW) Cox models to explore the association between statin use and VF.
We included 19,324 veterans. Median follow-up until the first viral rebound was 15 months (IQR: 6-40); 55% experienced VF. Almost 1/3 patients ever used statins but exposure was discontinuous with only 41% of follow-up time covered after initial exposure. The unadjusted hazard ratio (HR) for VF for current statin use was 0.60 (95%CI: 0.56-0.65). This association persisted after multivariate adjustment for demographics, HIV and cART parameters [HR 0.81 (CI: 0.75-0.88), p<0.001] and IPW [HR: 0.86 (CI: 0.78-0.96), p=0.001, see Table]. This was not observed for current use of other CVMs. The PDC model yielded similar results (not shown). There was no independent association between ever-statin use and VF.
Current statin exposure reduces the risk of VF in univariate, multivariate and inverse-probability-weighted models suggesting that statins have a modest antiviral activity in vivo. Whether this effect is direct or mediated by their anti-inflammatory properties merits further evaluation. In addition to their cardiovascular benefits, statins could increase the durability of successful antiretroviral therapy.