Sex Differences in Select Non-communicable HIV-Associated Comorbidities: Exploring the Role of Systemic Immune Activation/Inflammation.

Abstract

The goals of this review are to (1) explore HIV-associated cardiovascular disease (CVD), neurocognitive impairment, and non-AIDS-defining cancers (NADC) as heterogeneous model disease states fuelled in part by systemic immune activation/inflammation; (2) consider sex differences in the epidemiology of these diseases in both high-resource and lower-resource settings; and (3) examine biological and environmental factors which may contribute to heightened systemic immune activation/inflammation specifically among women living with HIV (WLHIV). The observation that WLHIV have higher levels of systemic immune activation/inflammation than men living with HIV (MLHIV) may be relevant to sex differences in select non-communicable HIV-associated comorbidities. Heightened systemic immune activation among WLHIV may be influenced by sex-specific responses to the virus and to immunomodulatory agents, as well as by behavioral choices/comorbid conditions and perturbations in the hypothalamic-pituitary-gonadal axis. Additional research is needed to elucidate region-specific drivers of heightened systemic immune activation/inflammation among WLHIV and to determine whether WLHIV who present with one immune-mediated HIV-associated comorbidity (e.g., cognitive impairment) may be at increased risk for another (e.g., CVD, NADC). This kind of research would facilitate improved risk prediction for non-communicable HIV-associated comorbidities among WLHIV and the development of targeted immunomodulatory prevention strategies.