A randomized pilot trial to evaluate the benefit of the concomitant use of atorvastatin and Raltegravir on immunological markers in protease-inhibitor-treated subjects living with HIV

PLoS One. 2020 Sep 17;15(9):e0238575. doi: 10.1371/journal.pone.0238575. eCollection 2020.

Abstract

Objective: Optimization of antiretroviral therapy and anti-inflammatory treatments, such as statins, are among the strategies aimed at reducing metabolic disorders, inflammation and immune activation in people living with HIV (PLWH). We evaluated the potential benefit of combining both strategies.

Design: Forty-two PLWH aged ≥40 years receiving a protease inhibitor (PI)-based regimen were randomized (1:1) to switch from PI to Raltegravir (n = 20), or to remain on PI (n = 22). After 24 weeks, all patients received atorvastatin 20mg/day for 48 weeks.

Methods: We analyzed plasma inflammatory as well as T-cell maturation, activation, exhaustion and senescence markers at baseline, 24 and 72 weeks.

Results: Plasma inflammatory markers remained unchanged. Furthermore, no major changes on T-cell maturation subsets, immunoactivation, exhaustion or immunosenescence markers in both CD4 and CD8 T cell compartments were observed. Only a modest decrease in the frequency of CD38+ CD8 T cells and an increase in the frequency of CD28-CD57+ in both CD4 and CD8 T-cell compartments were noticed in the Raltegravir-switched group.

Conclusions: The study combined antiretroviral switch to Raltegravir and Statin-based anti-inflammatory strategies to reduce inflammation and chronic immune activation in PLWH. Although this combination was safe and well tolerated, it had minimal impact on inflammatory and immunological markers.

Clinical trials registration: NCT02577042.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / therapeutic use*
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / therapeutic use*
  • Atorvastatin / administration & dosage
  • Atorvastatin / therapeutic use*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / therapeutic use*
  • Humans
  • Immunosenescence / drug effects
  • Inflammation / blood
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Lymphocyte Activation / drug effects
  • Male
  • Middle Aged
  • Pilot Projects
  • Raltegravir Potassium / administration & dosage
  • Raltegravir Potassium / therapeutic use*

Substances

  • Anti-HIV Agents
  • Anticholesteremic Agents
  • HIV Protease Inhibitors
  • Raltegravir Potassium
  • Atorvastatin

Associated data

  • ClinicalTrials.gov/NCT02577042

Grants and funding

This study was funded by Merk Sharp & Dome (MSD) through the MSD Investigator Studies Program (IIS # 52754), grant to EN. Sponsors or funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.