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Statins not linked to lower HIV persistence, inflammation, or immune activation
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22nd International AIDS Conference, Amsterdam, Netherlands, July 23-27, 2018
Mark Mascolini
In a study of 303 people with an undetectable viral load for at least 3 years, statin use did not predict lower levels of markers of HIV persistence, immune activation, or inflammation [1]. Veterans Affairs and AIDS Clinical Trials Group (ACTG) researchers who conducted this study believe their findings "do not support a major role for statins in reducing HIV persistence, although an early transient effect cannot be excluded."
Lipid-lowering statins are well known for their antiinflammatory and immune-modulating activity. Previous work by some of these investigators tied statin use to a lower risk of virologic rebound in people taking antiretroviral therapy (ART) [2]. The new study aimed to determine whether taking statins affects levels of markers indicating HIV persistence, inflammation, or immune activation.
The analysis involved samples collected from HIV-positive participants in ACTG protocol A5321 who started ART during chronic infection and kept their viral load below 50 copies for at least 3 years. The investigators measured 3 markers of HIV persistence: cell-associated HIV RNA, cell-associated HIV DNA, and single-copy assay plasma HIV RNA. They also determined levels of several inflammation/activation markers: IL-6, IP-10, neopterin, sCD14, sCD163, and TNF-alpha.
The analysis involved 303 people with 3 or more years of virologic suppression, including 72 (24%) taking a statin when they entered study A5321 and 231 not on a statin. Similar proportions in the statin and nonstatin groups (about 82%) were men. People taking a statin were older when they entered A5321 (median 53 versus 46 years), included a higher proportion of whites (64% versus 53%), and had taken ART longer before entering A5321 (median 8.1 versus 7.3 years).
Levels of the three measures of viral persistence did not differ significantly between the statin group and the nonstatin group, even after adjustment for sex, pre-ART CD4 count and viral load, CD4 count at study entry, HCV status, antiretroviral regimen, years on ART, and other variables.
Among the 6 inflammation/activation markers, only IP-10 differed significantly between groups, with a higher level in statin users (median 137.2 versus 117.7 pg/mL, P = 0.028). The researchers suggested the IP-10 difference could reflect "statin-induced repression of dendritic cell maturation, inducing tolerogenic dendritic cells that secrete high levels of interleukin 10 and IP-10."
The researchers concluded that in people taking long-term suppressive ART, statin use is not associated with markers of HIV persistence, inflammation, or immune activation. They called for randomized studies to confirm these results.
References
1. Bedimo R, Mar H, Bosch R, et al. Statin use during effective ART is not associated with lower biomarkers of HIV persistence or immune activation/inflammation. AIDS 2018: 22nd International AIDS Conference, Amsterdam, Netherlands, July 23-27, 2018. Abstract THPEB100. https://programme.aids2018.org//PAGMaterial/eposters/4312.pdf .
2. Drechsler H, Ayers C, Cutrell J, Maalouf N, Tebas P, Bedimo R. Current use of statins reduces risk of HIV rebound on suppressive HAART. PLoS One. 2017;12:e0172175. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172175
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Simvastatin reduces the expression of pro-inflammatory cytokines such as IL-6, IL-8, and MCP-1 in peripheral blood mononuclear cells from patients with hypercholesterolemia, both in vitro and in vivo [74]......https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394171/
Statins also cause decreased macrophage expression of soluble intercellular adhesion molecule-1 and lipopolysaccharide-induced secretion of IL-6 and TNF-α by monocytes and macrophages [34,35,36]. Recent data show that simvastatin therapy for 8 weeks reduces monocyte expression of TNF-α and IL-1β by 49 and 35%, respectively [37]; this is intriguing data because elevated plasma levels of both soluble intercellular adhesion molecule-1 and IL-6 have been shown to predict risk for myocardial infarction [12,13]. A recent analysis from the Cholesterol and Recurrent Events (CARE) trial showed that plasma concentrations of TNF-α are also persistently elevated among postmyocardial infarction patients at increased risk for coronary events [38]. These findings provide supportive evidence that anti-inflammatory effects of statins may make an important contribution to their clinical efficacy......https://www.ncbi.nlm.nih.gov/pmc/articles/PMC59622/
Treatment ex vivo with simvastatin and atorvastatin reduced the proportion of CD16+ monocytes in peripheral blood mononuclear cells, as well as in purified monocytes, especially CD14++CD16+ "intermediate" monocytes most closely associated with neurocognitive disease. Statin treatment also markedly reduced expression of CD163, which is also linked to HAND pathogenesis.....https://www.ncbi.nlm.nih.gov/pubmed/27021071
Statin use during effective ART is not associated with lower biomarkers of
HIV persistence or immune activation/inflammation
R. Bedimo1,2, H. Mar3, R. Bosch3, H. Drechsler1,2, J. Cyktor4, B. Macatangay4, C. Lalama3, C. Rinaldo4, A. Collier5, C. Godfrey6, E. Hogg7, C. Hensel8, J. Eron9, D. McMahon4, J. Mellors4,
P. Tebas10, R. Gandhi11, and the A5321 Study Team
1VA North Texas Health Care System, Dallas, TX, 2University of Texas Southwestern Medical Center, Dallas, TX, 3Harvard School of Public Health, Boston, MA 4University of Pittsburgh, Pittsburgh, PA, 5University of Washington, Seattle, WA, 6Division of AIDS, NIAID, NIH, Washington, DC,
7Social & Scientific Systems, Silver Spring, MA, 8Frontier Science & Technology Research Foundation, Inc, Amherst, NY, 9University of North Carolina, Chapel Hill, NC 10University of Pennsylvania, Philadelphia, PA, 11Massachusetts General Hospital, Boston, MA
Statin use during effective ART is not associated with lower biomarkers of HIV persistence or immune activation/inflammation
R. Bedimo1,2, H. Mar3, R. Bosch3, H. Drechsler1,2, J. Cyktor4, B. Macatangay4, C. Lalama3, C. Rinaldo4, A. Collier5, C. Godfrey6, E. Hogg7, C. Hensel8, J. Eron9, D. McMahon4, J. Mellors4, P. Tebas10, R. Gandhi11, and the A5321 Study Team
1VA North Texas Health Care System, Dallas, TX, 2University of Texas Southwestern Medical Center, Dallas, TX, 3Harvard School of Public Health, Boston, MA 4University of Pittsburgh, Pittsburgh, PA, 5University of Washington, Seattle, WA, 6Division of AIDS, NIAID, NIH, Washington, DC, 7Social & Scientific Systems, Silver Spring, MA, 8Frontier Science & Technology Research Foundation, Inc, Amherst, NY, 9University of North Carolina, Chapel Hill, NC 10University of Pennsylvania, Philadelphia, PA, 11Massachusetts General Hospital, Boston, MA
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