Platelet activation in adult HIV-infected patients on antiretroviral therapy: a systematic review and meta-analysis

Nkambule, Bongani B.; Mxinwa, Vuyolwethu; Mkandla, Zibusiso; Mutize, Tinashe; Mokgalaboni, Kabelo; Nyambuya, Tawanda M.; Dludla, Phiwayinkosi V.

doi:10.1186/s12916-020-01801-9

Cited by 19 publications

(25 citation statements)

References 48 publications

(173 reference statements)

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“…Several investigations have found that patients living with HIV have higher levels of P-selectin than people who are not infected. This backs up the observation that adult HIV-infected patients have higher levels of platelet activation [ 37 ]. Importantly, these levels were found to persist in follow-up investigations after 3 to 24 months of effective ART [ 38 ].…”

Section: P-selectin In Human Diseasesmentioning

confidence: 87%

The Role of P-Selectin in COVID-19 Coagulopathy: An Updated Review

Agrati

Sacchi

Tartaglia

et al. 2021

IJMS

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In severe COVID-19, which is characterized by blood clots and neutrophil-platelet aggregates in the circulating blood and different tissues, an increased incidence of cardiovascular complications and venous thrombotic events has been reported. The inflammatory storm that characterizes severe infections may act as a driver capable of profoundly disrupting the complex interplay between platelets, endothelium, and leukocytes, thus contributing to the definition of COVID-19-associated coagulopathy. In this frame, P-selectin represents a key molecule expressed on endothelial cells and on activated platelets, and contributes to endothelial activation, leucocyte recruitment, rolling, and tissue migration. Briefly, we describe the current state of knowledge about P-selectin involvement in COVID-19 pathogenesis, its possible use as a severity marker and as a target for host-directed therapeutic intervention.

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Section: P-selectin In Human Diseasesmentioning

confidence: 87%

The Role of P-Selectin in COVID-19 Coagulopathy: An Updated Review

Agrati

Sacchi

Tartaglia

et al. 2021

IJMS

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“…Next, we analyzed the phenotype of platelet-CD4 + T cell aggregates in patients infected with HIV-1. Previous reports have demonstrated that HIV-1-infected patients display elevated platelet activation with or without ART (28,56). The activation state of platelets in platelet-CD4 + T cell aggregates was analyzed by detecting CD62P expression.…”

Section: Discussionmentioning

confidence: 99%

Increased Platelet-CD4+ T Cell Aggregates Are Correlated With HIV-1 Permissiveness and CD4+ T Cell Loss

Dai

Cheng

et al. 2021

Front. Immunol.

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Chronic HIV-1 infection is associated with persistent inflammation, which contributes to disease progression. Platelet-T cell aggregates play a critical role in maintaining inflammation. However, the phenotypic characteristics and clinical significance of platelet-CD4+ T cell aggregates remain unclear in different HIV-infected populations. In this study, we quantified and characterized platelet-CD4+ T cell aggregates in the peripheral blood of treatment-naïve HIV-1-infected individuals (TNs), immunological responders to antiretroviral therapy (IRs), immunological non-responders to antiretroviral therapy (INRs), and healthy controls (HCs). Flow cytometry analysis and immunofluorescence microscopy showed increased platelet-CD4+ T cell aggregate formation in TNs compared to HCs during HIV-1 infection. However, the frequencies of platelet-CD4+ T cell aggregates decreased in IRs compared to TNs, but not in INRs, which have shown severe immunological dysfunction. Platelet-CD4+ T cell aggregate frequencies were positively correlated with HIV-1 viral load but negatively correlated with CD4+ T cell counts and CD4/CD8 ratios. Furthermore, we observed a higher expression of CD45RO, HIV co-receptors, HIV activation/exhaustion markers in platelet-CD4+ T cell aggregates, which was associated with HIV-1 permissiveness. High levels of caspase-1 and caspase-3, and low levels of Bcl-2 in platelet-CD4+ T cell aggregates imply the potential role in CD4+ T cell loss during HIV-1 infection. Furthermore, platelet-CD4+ T cell aggregates contained more HIV-1 gag viral protein and HIV-1 DNA than their platelet-free CD4+ T cell counterparts. The platelet-CD4+ T cell aggregate levels were positively correlated with plasma sCD163 and sCD14 levels. Our findings demonstrate that platelet-CD4+ T cell aggregate formation has typical characteristics of HIV-1 permissiveness and is related to immune activation during HIV-1 infection.

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“…There is increased platelet activity leading to increased immune activation in PLHIV, which is associated with the increased CVD risk. This increased platelet activity is not completely abolished by ARV drugs, 30 36 and indeed, there are reports that ARV drugs may enhance platelet activation. 30 37–39 Therefore, low-dose ASA added onto ARV drugs may be the more appropriate intervention than high-dose ASA for reducing CVD risk in PLHIV.…”

Section: Introductionmentioning

confidence: 88%

“…[37][38][39] Protease inhibitor (PI)-based ART has also been implicated in increasing platelet activation with patients on PI-based ART having up to double levels of platelet activation compared with ARV naïve counterparts. 30 In view of this possible drawback of ARV drugs on immune and platelet activation, an additional drug may be necessary for effective prevention of non-infectious comorbidities including CVD in HIV infection. 29 Aspirin or acetylsalicylic acid (ASA) is a drug with antiplatelet and anti-inflammatory properties.…”

Section: Introductionmentioning

confidence: 99%

“…In some reports, sP-selectin levels normalise to non-HIV-infected levels with ARV drugs, 34 while in other reports, the levels do not decrease 35 or do not normalise to non- HIV infected levels. 30 36 In fact, abacavir-based ARV regimen has been reported to cause enhancement of platelet activation and platelet hyperactivity. 37–39 Protease inhibitor (PI)-based ART has also been implicated in increasing platelet activation with patients on PI-based ART having up to double levels of platelet activation compared with ARV naïve counterparts.…”

Section: Introductionmentioning

confidence: 99%

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Effect of aspirin on HIV disease progression among HIV-infected individuals initiating antiretroviral therapy: study protocol for a randomised controlled trial

et al. 2021

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IntroductionAn increase in cardiovascular disease (CVD) among people living with HIV infection is linked to platelet and immune activation, a phenomenon unabolished by antiretroviral (ARV) drugs alone. In small studies, aspirin (acetylsalicylic acid [ASA]) has been shown to control immune activation, increase CD4+ count, halt HIV disease progression and reduce HIV viral load (HVL). We present a protocol for a larger ongoing randomised placebo controlled trial on the effect of an addition of ASA to ARV drugs on HIV disease progression.Methods and analysisA single-centre phase IIA double-blind, parallel-group randomised controlled trial intends to recruit 454 consenting ARV drug-naïve, HIV-infected adults initiating ART. Participants are randomised in blocks of 10 in a 1:1 ratio to receive, in addition to ARV drugs, 75 mg ASA or placebo for 6 months. The primary outcome is the proportion of participants attaining HVL of <50 copies/mL by 8, 12 and 24 weeks. Secondary outcomes include proportions of participants with HVL of >1000 copies/mL at week 24, attaining a >30% rise of CD4 count from baseline value at week 12, experiencing adverse events, with normal levels of biomarkers of platelet and immune activation at weeks 12 and 24 and rates of morbidity and all-cause mortality. Intention-to-treat analysis will be done for all study outcomes.Ethics and disseminationEthical approval has been obtained from institutional and national ethics review committees. Findings will be submitted to peer-reviewed journals and presented in scientific conferences.Trial registration numberPACTR202003522049711.

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Platelet activation in adult HIV-infected patients on antiretroviral therapy: a systematic review and meta-analysis

Cited by 19 publications

References 48 publications

The Role of P-Selectin in COVID-19 Coagulopathy: An Updated Review

The Role of P-Selectin in COVID-19 Coagulopathy: An Updated Review

Increased Platelet-CD4+ T Cell Aggregates Are Correlated With HIV-1 Permissiveness and CD4+ T Cell Loss

Effect of aspirin on HIV disease progression among HIV-infected individuals initiating antiretroviral therapy: study protocol for a randomised controlled trial

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