Consistent use of lipid lowering therapy in HIV infection is associated with low mortality

Abstract

Background In people living with HIV (PLWH), statins may be disproportionately effective but remain underutilized. A large prospective trial in patients with low to moderate cardiovascular (ASCVD) risk will reveal whether they should be considered in all PLWH. But its effect size may not apply to real-world PLWH with higher ASCVD and mortality risk. Also, the clinical role of non-statin lipid-lowering therapy (LLT) and LLT adherence in this population is unknown. Methods Comparative multi-level marginal structural model for all-cause mortality examining four time-updated exposure levels to LLT, antihypertensives, and aspirin in a virtual cohort of older PLWH. Incident coronary, cerebrovascular, and overall ASCVD events, serious infections, and new cancer diagnoses served as explanatory outcomes. Results In 23,276 HIV-infected US-veterans who were followed for a median of 5.2 years after virologic suppression overall mortality was 33/1000 patient years: > 3 times higher than in the US population. Use of antihypertensives or aspirin was associated with increased mortality. Past LLT use (> 1 year ago) had no effect on mortality. LLT exposure in the past year was associated with a reduced hazard ratio (HR) of death: 0.59, 95% confidence interval (CI) 0.51–0.69, p < 0.0001 for statin containing LLT and 0.71 (CI: 0.54–0.93), p = 0.03 for statin-free LLT. For consistent LLT use (> 11/12 past months) the HR of death was 0.48 (CI: 0.35–0.66) for statin-only LLT, 0.34 (CI: 0.23–0.52) for combination LLT, and 0.27 (CI: 0.15–0.48) for statin-free LLT (p < 0.0001 for all). The ASCVD risk in these patients was reduced in similar fashion. Use of statin containing LLT was also associated with reduced infection and cancer risk. Multiple contrasting subgroup analyses yielded comparable results. Confounding is unlikely to be a major contributor to our findings. Conclusions In PLWH, ongoing LLT use may lead to substantially lower mortality, but consistent long-term adherence may be required to reduce ASCVD risk. Consistent non-statin LLT may be highly effective and should be studied prospectively.

Retrospective cohort study of statin prescribing for primary prevention among people living with HIV

“…Registry data of PLWH within the U.S. Veterans Affairs system notes a 52% mortality reduction among PLWH with consistent statin use. 24 Additionally, lack of randomized, controlled trials within this patient population led to the currently ongoing trial of pitavastatin, known as the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) trial. 25 The REPRIEVE trial will be the first to specifically evaluate major adverse cardiovascular events (MACE) in over 7,500 primary prevention PLWH initiated on a moderate-intensity statin or placebo.…”

Influence of Statin Therapy on the Incidence of Cardiovascular Events, Cancer, and All-Cause Mortality in People Living With HIV: A Meta-Analysis

“…Sensitivity analysis by excluding one study at a time showed consistent results (RR: 0.98 to 1.25, p > 0.05). However, a meta-analysis of the four studies (23,25,30,31) showed that statin use was significantly related to a reduced risk of cancer in PLWH (RR: 0.73, 95% CI: 0.58 to 0.93, p = 0.009, I 2 = 49%; Figure 2C). Sensitivity analyses by excluding one study at a time also showed consistent results (RR: 0.64 to 0.78, p < 0.05).…”

“…It was shown that a total of 5,320 studies were obtained after literature search in the Medline, the Embase, and the Web of Science databases after excluding of the duplicated records, while 504 of them were excluded based on the titles and abstracts primarily because they were irrelevant studies. Then, 16 of the 28 potentially relevant studies were further excluded based on full-text review according to the reasons listed in Figure 1 and the other 12 studies were finally included (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32).…”

“…In addition, previous meta-analyses have confirmed the efficacy and safety of statins in improving lipid profile in PLWH (19,20). However, studies evaluating the influence of statin therapy on the risk of CV events, cancer, and all-cause mortality in PLWH showed inconsistent results (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). Some studies suggested the benefits of statins on the above outcomes (22,25,30,31), while other studies did not suggest any benefits of statins (21,23,24,(26)(27)(28)(29)32).…”

“…However, studies evaluating the influence of statin therapy on the risk of CV events, cancer, and all-cause mortality in PLWH showed inconsistent results (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). Some studies suggested the benefits of statins on the above outcomes (22,25,30,31), while other studies did not suggest any benefits of statins (21,23,24,(26)(27)(28)(29)32). Therefore, we performed a meta-analysis to systematically evaluate the efficacy of statin on the risk of CV events, cancer, and all-cause mortality in PLWH.…”