Abstract
Purpose of ReviewThis review will outline the multilevel effects of biological sex on HIV acquisition, pathogenesis, treatment response, and prospects for cure. Potential mechanisms will be discussed along with future research directions.Recent FindingsHIV acquisition risk is modified by sex hormones and the vaginal microbiome, with the latter acting through both inflammation and local metabolism of pre-exposure prophylaxis drugs. Female sex associates with enhanced risk for non-AIDS morbidities including cardiovascular and cerebrovascular disease, suggesting different inflammatory profiles in men and women. Data from research on HIV cure points to sex differences in viral reservoir dynamics and a direct role for sex hormones in latency maintenance.SummaryBiological sex remains an important variable in determining the risk of HIV infection and subsequent viral pathogenesis, and emerging data suggest sex differences relevant to curative interventions. Recruitment of women in HIV clinical research is a pathway to both optimize care for women and to identify novel therapeutics for use in both men and women.
Highlights
A combination of environmental factors, host genetics, and viral features determines the acquisition and pathogenesis of HIV infection
Research defining sex differences serves a dual purpose: first, defining sex-specific responses will insure that interventions have efficacy in both men and women, and second, differences may highlight pathways that can be modulated in both sexes to optimize treatment and prevention and curative interventions
Sex differences in HIV arise from the combinatorial effects of sex hormones, genetic differences, and sociobehavioral and environmental influences
Summary
A combination of environmental factors, host genetics, and viral features determines the acquisition and pathogenesis of HIV infection. This review will address sex-specific features of HIV prevention, pathogenesis, and cure research, and outline potential biological mechanisms for these differences. The data suggest that there are sex-specific features of risk perception and medication adherence, along with critical differences in pharmacologic properties and the microenvironment at sites of acquisition in men and women.
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