BackgroundCardio-metabolic risk factors are of increasing concern in HIV-infected individuals, particularly with the advent of antiretroviral therapy (ART) and the subsequent rise in longevity. However, the prevalence of cardio-metabolic abnormalities in this population and the differential contribution, if any, of HIV specific factors to their distribution, are poorly understood. Therefore, we conducted a systematic review and meta-analysis to estimate the global prevalence of metabolic syndrome (MS) in HIV-infected populations, its variation by the different diagnostic criteria, severity of HIV infection, ART used and other major predictive characteristics.MethodsWe performed a comprehensive search on major databases for original research articles published between 1998 and 2015. The pooled overall prevalence as well as by specific groups and subgroups were computed using random effects models.ResultsA total of 65 studies across five continents comprising 55094 HIV-infected participants aged 17–73 years (median age 41 years) were included in the final meta-analysis. The overall prevalence of MS according to the following criteria were: ATPIII-2001:16.7% (95%CI: 14.6–18.8), IDF-2005: 18% (95%CI: 14.0–22.4), ATPIII-2004-2005: 24.6% (95%CI: 20.6–28.8), Modified ATPIII-2005: 27.9% (95%CI: 6.7–56.5), JIS-2009: 29.6% (95%CI: 22.9–36.8), and EGIR: 31.3% (95%CI: 26.8–36.0). By some MS criteria, the prevalence was significantly higher in women than in men (IDF-2005: 23.2% vs. 13.4, p = 0.030), in ART compared to non-ART users (ATPIII-2001: 18.4% vs. 11.8%, p = 0.001), and varied significantly by participant age, duration of HIV diagnosis, severity of infection, non-nucleoside reverse transcriptase inhibitors (NNRTIs) use and date of study publication. Across criteria, there were significant differences in MS prevalence by sub-groups such as in men, the Americas, older publications, regional studies, younger adults, smokers, ART-naïve participants, NNRTIs users, participants with shorter duration of diagnosed infection and across the spectrum of HIV severity. Substantial heterogeneities across and within criteria were not fully explained by major study characteristics, while evidence of publication bias was marginal.ConclusionsThe similar range of MS prevalence in the HIV-infected and general populations highlights the common drivers of this condition. Thus, cardio-metabolic assessments need to be routinely included in the holistic management of the HIV-infected individual. Management strategies recommended for MS in the general population will likely provide similar benefits in the HIV-infected.

Platelets are non-nucleated cells that play central roles in the processes of hemostasis, innate immunity, and inflammation; however, several reports show that these distinct functions are more closely linked than initially thought. Platelets express numerous receptors and contain hundreds of secretory products. These receptors and secretory products are instrumental to the platelet functional responses. The capacity of platelets to secrete copious amounts of cytokines, chemokines, and related molecules appears intimately related to the role of the platelet in inflammation. Platelets exhibit non-self-infectious danger detection molecules on their surfaces, including those belonging to the “toll-like receptor” family, as well as pathogen sensors of other natures (Ig- or complement receptors, etc.). These receptors permit platelets to both bind infectious agents and deliver differential signals leading to the secretion of cytokines/chemokines, under the control of specific intracellular regulatory pathways. In contrast, dysfunctional receptors or dysregulation of the intracellular pathway may increase the susceptibility to pathological inflammation. Physiological vs. pathological inflammation is tightly controlled by the sensors of danger expressed in resting, as well as in activated, platelets. These sensors, referred to as pathogen recognition receptors, primarily sense danger signals termed pathogen associated molecular patterns. As platelets are found in inflamed tissues and are involved in auto-immune disorders, it is possible that they can also be stimulated by internal pathogens. In such cases, platelets can also sense danger signals using damage associated molecular patterns (DAMPs). Some of the most significant DAMP family members are the alarmins, to which the Siglec family of molecules belongs. This review examines the role of platelets in anti-infection immunity via their TLRs and Siglec receptors.

This study demonstrates the putative participation of PLT-derived sOX40L, IL-27, and sCD40L, which accumulate in PC supernatants, with inflammatory-type ATRs. Further studies are required to determine the clinical significance of these findings to forecast preventive measures whenever possible.

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