Evaluating the effect of atorvastatin exposure and vitamin D levels on lipid outcomes in people with HIV-1 with suppressed HIV-1 RNA and LDL cholesterol <130 mg/dL

HIV Med. 2023 Jun;24(6):749-753. doi: 10.1111/hiv.13453. Epub 2022 Dec 22.

Abstract

Introduction: Cardiovascular disease (CVD) has become a leading cause of morbidity and mortality among people with HIV. Atorvastatin is known to reduce cardiovascular risk. We (1) compared atorvastatin concentrations between different boosted protease inhibitors (PIs) and with lipid outcomes and (2) compared pre-atorvastatin 25-OH vitamin D levels with atorvastatin concentrations and with lipid outcomes, in people with HIV with suppressed HIV-1 RNA and low-density lipoprotein cholesterol (LDL-C) <130 mg/dL.

Methods: A5275 was a randomized, double-blind, placebo-controlled crossover study of atorvastatin in virally suppressed people with HIV with fasting LDL-C <130 mg/dL. We analyzed results over the 20 weeks of active atorvastatin treatment. Atorvastatin was initiated at 10 mg daily and increased to 20 mg daily after 4 weeks if there were no findings of toxicity. Atorvastatin trough concentrations were measured at week 20. Participants took combination antiretroviral therapy (ART) that included a boosted PI throughout.

Results: Overall (n = 67), 70% of participants were male, and the median age was 51 years. There was no apparent association between atorvastatin trough concentrations and pre-atorvastatin vitamin D levels (r = 0.01, p = 0.9) or by boosted PI (p = 0.20). Median pre- to post-atorvastatin change was -39.0 mg/dL in fasting total cholesterol, -40.4 ng/mL in lipoprotein-associated phospholipase A2 (LP-PLA2), and -13.8 U/L in oxidized LDL, with all changes negatively correlated with atorvastatin trough concentrations (r = -0.19, -0.09, -0.21; p ≥ 0.096).

Conclusions: No apparent associations between pre-atorvastatin vitamin D levels and outcomes were observed (all p > 0.70). In virologically suppressed people with HIV, higher atorvastatin concentrations were marginally associated with greater decreases in lipid outcomes.

Trial registration: ClinicalTrials.gov NCT01351025.

Keywords: Vitamin D; cardiovascular disease; low-density lipoprotein cholesterol (LDL); protease inhibitors; statin.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anticholesteremic Agents*
  • Atorvastatin / pharmacology
  • Cholesterol, LDL
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • HIV Infections* / drug therapy
  • HIV-1*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Male
  • Middle Aged
  • Treatment Outcome
  • Vitamin D

Substances

  • Atorvastatin
  • Cholesterol, LDL
  • Vitamin D
  • Anticholesteremic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors

Associated data

  • ClinicalTrials.gov/NCT01351025