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Consistent use of lipid lowering therapy in HIV infection is associated with low mortality
Henning Drechsler1,2, Colby Ayers3, James Cutrell3
1VA North Texas Health Care System, Dallas, TX, USA. Henning.Drechsler@va.gov.
Insights
Lipid-lowering therapy (LLT) significantly reduces mortality and cardiovascular risk in people living with HIV (PLWH). Consistent adherence to LLT, including non-statin options, is crucial for long-term health benefits in this population.
Area of Science:
- Cardiovascular Medicine
- Infectious Diseases
- Pharmacology
Background:
- Statins show potential benefits for people living with HIV (PLWH), but their utilization is suboptimal.
- Existing trials may not reflect the higher cardiovascular (ASCVD) and mortality risks in real-world PLWH populations.
- The roles of non-statin lipid-lowering therapy (LLT) and adherence in PLWH require further investigation.
Purpose of the Study:
- To evaluate the impact of lipid-lowering therapy (LLT) on all-cause mortality and ASCVD events in a cohort of older people living with HIV (PLWH).
- To assess the association between different types of LLT (statin-containing vs. statin-free) and adherence levels with health outcomes.
- To explore the effects of LLT on serious infections and new cancer diagnoses in PLWH.
Main Methods:
- A comparative multi-level marginal structural model was employed using a virtual cohort of 23,276 HIV-infected US veterans.
- Time-updated exposure levels to LLT, antihypertensives, and aspirin were analyzed.
- Outcomes included all-cause mortality, incident coronary, cerebrovascular, and overall ASCVD events, serious infections, and new cancer diagnoses.
Main Results:
- Overall mortality in PLWH was over three times higher than in the general US population.
- Recent LLT use (within the past year) was associated with reduced mortality (HR 0.59 for statin-LLT, HR 0.71 for non-statin LLT).
- Consistent LLT use (over 11/12 months) demonstrated significant mortality reduction (HR 0.48 for statin-only, HR 0.34 for combination, HR 0.27 for non-statin LLT), with similar ASCVD risk reduction. Statin-containing LLT also lowered infection and cancer risk.
Conclusions:
- Ongoing LLT use can substantially decrease mortality in people living with HIV (PLWH).
- Consistent long-term adherence to LLT is likely necessary for significant ASCVD risk reduction.
- Consistent use of non-statin LLT shows high efficacy and warrants prospective study in PLWH.
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.
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