Rosuvastatin Treatment Reduces Markers of Monocyte Activation in HIV-Infected Subjects on Antiretroviral Therapy

Funderburg, Nicholas T.; Jiang, Ying; Debanne, Sara M.; Storer, Norma; Labbato, Danielle; Clagett, Brian; Robinson, Janet; Lederman, Michael M.; McComsey, Grace A.

doi:10.1093/cid/cit748

Cited by 125 publications

(134 citation statements)

References 47 publications

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“…[22][23][24] Increased immune activation of monocytes was reported to be involved in HIV-1 pathogenesis and thus associated with CVD risk. 17,28,29 In the present study, we demonstrated that in contrast to the decreased percentage of CD14 high CD16 2 monocyte subset, CD14 dim CD16 1 and CD14 high CD16 1 monocyte subsets were expanded during both primary and chronic HIV-1 infection. This was the first report of the monocyte subset distribution in primary HIV-1 infection, and it expanded previous observations that had focused on chronic HIV-1-infected patients, HARRT patients, and elite controllers.…”

Section: Monocyte Subset Frequencies Are Altered During Hiv-1 Infectionsupporting

confidence: 45%

Higher levels of circulating monocyte–platelet aggregates are correlated with viremia and increased sCD163 levels in HIV-1 infection

Liang

Duan

et al. 2014

Cell Mol Immunol

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Increased levels of monocyte-platelet aggregates (MPAs) are reported to be highly correlated with cardiovascular events. In this study, the MPA levels in different monocyte subsets and the associations between MPA levels, HIV-1 viremia and monocyte activation were evaluated during HIV-1 infection. The results showed that the percentages of MPAs in all three monocyte subsets were higher in HIV-1-infected subjects than in healthy controls, and were associated with the plasma viral load in the non-classical and intermediate monocyte subsets. The plasma levels of sCD14 and sCD163 were upregulated in HIV-1 infection and were positively associated with viral loads and negatively associated with CD4 counts. P-selectin glycoprotein ligand-1 (PSGL-1) was shown to be expressed at significantly lower levels on all three monocyte subsets and was negatively correlated with the sCD163 level. The MPA level was correlated with the levels of plasma sCD163 but negatively correlated with CD163 and PSGL-1 on all three monocyte subsets. An elevated immune activation status was correlated with increased MPA formation, underlying the potential interaction between monocyte activation and MPA formation. This interaction may be related to a higher thromboembolic risk in patients infected with HIV-1.

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Section: Monocyte Subset Frequencies Are Altered During Hiv-1 Infectionsupporting

confidence: 45%

Higher levels of circulating monocyte–platelet aggregates are correlated with viremia and increased sCD163 levels in HIV-1 infection

Liang

Duan

et al. 2014

Cell Mol Immunol

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“…C'è una sufficiente evidenza scientifica che nella popolazione generale le statine possono rallentare la progressione della malattia aterosclerotica e ridurre l'incidenza di eventi cardiovascolari, non solo tramite la loro azione ipolipemizzante, ma anche attraverso un effetto anti-infiammatorio e immuno-modulatorio. Recenti studi hanno dimostrato che le statine possono ridurre in modo significativo i livelli sierici di alcuni marker infiammatori sistemici anche nei pazienti HIV-positivi, oltre alla velocità di progressione dell'aterosclerosi (43)(44)(45).…”

Section: Gestione Del Rischio Cardiovascolare: Terapia Ipolipemizzantunclassified

“…Lo studio randomizzato SATURN ha valutato gli effetti della rosuvastatina versus placebo in 147 soggetti HIV-positivi sottoposti a cART e con colesterolo LDL nella norma, ma evidenza di infiammazione o immunoattivazione sistemica. Dopo 6 mesi di trattamento, la rosuvastatina ha prodotto rispetto al placebo una riduzione significativa di alcuni marcatori di infiammazione e immunoattivazione (come CD14 solubile e fosfolipasi A2), ma non di altri (come proteina C-reattiva, IL-6 e D-dimero) (45,47). Anche la terapia anti-aggregante con acido acetilsalicilico ha evidenziato favorevoli effetti sull'immunoattivazione nei pazienti con infezione da HIV.…”

Section: Gestione Del Rischio Cardiovascolare: Terapia Ipolipemizzantunclassified

Gestione del rischio cardiovascolare nel paziente HIV positivo

Calza¹

2017

JHA

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RiassuntoDopo l'introduzione della moderna terapia antiretrovirale di combinazione (cART), l'infezione da HIV è divenuta una malattia cronica con un notevole prolungamento dell'attesa media di vita dei pazienti HIV-positivi. Di conseguenza le comorbosità tra cui le malattie cardiovascolari, hanno acquisito un'importanza via via crescente in questa popolazione. Nei pazienti con infezione da HIV si osserva infatti un rischio di infarto miocardico acuto significativamente più elevato rispetto alla popolazione generale, ma il meccanismo patogenetico di questa malattia aterosclerotica accelerata è complesso e certamente multifattoriale. La comparsa più frequente della malattia coronarica può essere la conseguenza di una maggiore prevalenza dei fattori di rischio tradizionali (che sono più frequenti tra i soggetti HIV-positivi), ma anche della replicazione diretta del virus e dell'effetto cardiotossico a lungo termine di alcuni farmaci antiretrovirali. Inoltre, nonostante la persistente soppressione della viremia indotta dalla cART generalmente si associ ad una riduzione del rischio cardiovascolare, numerosi studi hanno evidenziato in questi pazienti una condizione di infiammazione e di immunoattivazione cronica, che può condurre al danno endoteliale ed alla malattia aterosclerotica. La corretta gestione del rischio cardiovascolare e la prevenzione della malattia coronarica rappresentano oggi una sfida di primaria importanza per tutti i clinici coinvolti nella cura dei pazienti con infezione da HIV.

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“…Rosuvastatin reduced sCD14 and tissue factor expression on monocytes in HIV þ patients. 31 However, natalizumab is the only drug known to block leukocyte traffic and reduce inflammation.…”

Section: Anti-a4 Blocks Monocyte Traffic To Drgmentioning

confidence: 99%

α4-Integrin Antibody Treatment Blocks Monocyte/Macrophage Traffic to, Vascular Cell Adhesion Molecule-1 Expression in, and Pathology of the Dorsal Root Ganglia in an SIV Macaque Model of HIV-Peripheral Neuropathy

Lakritz

Thibault

Robinson

et al. 2016

The American Journal of Pathology

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Traffic of activated monocytes into the dorsal root ganglia (DRG) is critical for pathology in HIV peripheral neuropathy. We have shown that accumulation of recently recruited (bromodeoxyuridine þ MAC387 þ ) monocytes is associated with severe DRG pathology and loss of intraepidermal nerve fibers in SIV-infected macaques. Herein, we blocked leukocyte traffic by treating animals with natalizumab, which binds to a4-integrins. SIV-infected CD8-depleted macaques treated with natalizumab either early (the day of infection) or late (28 days after infection) were compared with untreated SIV-infected animals sacrificed at similar times. Histopathology showed diminished DRG pathology with natalizumab treatment, including decreased inflammation, neuronophagia, and Nageotte nodules. Natalizumab treatment resulted in a decrease in the number of bromodeoxyuridine þ (early), MAC387 þ (late), CD68 þ (early and late), and SIVp28 þ (late) macrophages in DRG tissues. The number of CD3 þ T lymphocytes in DRGs was not affected by natalizumab treatment. Vascular cell adhesion molecule 1, an adhesion molecule that mediates leukocyte traffic, was diminished in DRGs of all natalizumab-treated animals. These data show that blocking monocyte, but not T lymphocyte, traffic to the DRG results in decreased inflammation and pathology, supporting a role for monocyte traffic and activation in HIV peripheral neuropathy. The primary mechanisms of HIV peripheral neuropathy include immune damage secondary to viral infection and mitochondrial toxicity from the antiretrovirals. Because HIV and SIV do not productively infect neurons or Schwann cells, damage to the dorsal root ganglia (DRG) in peripheral neuropathy is believed to be, in part, because of infected and activated macrophages. In vitro and in vivo studies suggest that both viral proteins and systemic inflammation secondary to the viral infection may damage neurons and axons. 1 Using a CD8-depleted SIV-infected rhesus macaque model of peripheral neuropathy, we have shown that accumulation of recruited [bromodeoxyuridine (BrdU) þ MAC387 þ ] monocytes/macrophages was associated with severe DRG pathology. 2 The number of BrdU þ monocytes correlated with DRG histopathology, which included neuronophagia, satellitosis, and Nageotte nodules. 2 Our data demonstrate that newly recruited MAC387 þ BrdU þ macrophages play a significant role in DRG pathogenesis.

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Rosuvastatin Treatment Reduces Markers of Monocyte Activation in HIV-Infected Subjects on Antiretroviral Therapy

Abstract: NCT01218802.

Cited by 125 publications

References 47 publications

Higher levels of circulating monocyte–platelet aggregates are correlated with viremia and increased sCD163 levels in HIV-1 infection

Higher levels of circulating monocyte–platelet aggregates are correlated with viremia and increased sCD163 levels in HIV-1 infection

Gestione del rischio cardiovascolare nel paziente HIV positivo

α4-Integrin Antibody Treatment Blocks Monocyte/Macrophage Traffic to, Vascular Cell Adhesion Molecule-1 Expression in, and Pathology of the Dorsal Root Ganglia in an SIV Macaque Model of HIV-Peripheral Neuropathy

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