Sex Differences in CMV Replication and HIV Persistence During Suppressive ART

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>The association between subclinical CMV replication and HIV persistence has not been investigated in cis-gender women with HIV.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Fifty virologically suppressed female participants with HIV were prospectively enrolled and provided oral, vaginal, urine samples and peripheral blood mononuclear cells (PBMCs) at one cross-sectional time-point. Cytomegalovirus (CMV) DNA was quantified in each specimen by real-time PCR. Cellular HIV DNA and HIV RNA transcripts (unspliced and multiply spliced [ms] encoding tat-rev) were quantified by droplet digital (dd)PCR. Historical data from 49 male individuals with HIV and CMV were used as controls.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Levels of cellular HIV DNA and unspliced HIV RNA were not different between sexes, but female participants had less detectable msHIV RNA and CMV DNA compared to males (both P&amp;lt;0.01). Unlike previously described for males, the presence of CMV DNA was not associated with increased HIV DNA in females. Among female participants, pre-menopausal status was independently associated with lower HIV DNA compared to post-menopause, after adjusting for nadir CD4 count (P&amp;lt;0.01).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Female participants with HIV have reduced cellular HIV RNA and less subclinical CMV DNA compared to males, but overall similar HIV DNA levels in our study. Post-menopausal status was independently associated with higher HIV DNA levels among female participants.</jats:p> </jats:sec>

Sex differences in cytokine profiles during suppressive antiretroviral therapy

“…Stored plasma samples from 50 women (sex assigned at birth) with HIV on suppressive ART enrolled at Weill Cornell Medicine and 52 men (sex assigned at birth) with HIV on suppressive ART enrolled in the California Collaborative Treatment Group (CCTG) 592 were used in this study to investigate the cytokine differences in men and women with HIV. The studies were conducted with written consent and were approved by the Human Research Protections Program at the University of California, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, the University of Southern California, and Weill Cornell Medicine [19].…”

Sex differences in NK cells mediated by the X-linked epigenetic regulator UTX

“…Due to the critical role of NK cells in anti-viral immunity and increased male susceptibility to cytomegalovirus (CMV) and other herpesvirus family infections 4 , it was surprising that multiple studies have reported that human males display increased NK cell numbers [6][7][8][9][10] . A recent investigation examining spleens of C57BL/6 mice also reported increased numbers of NK cells in males vs. females 26 .…”

“…While males are less susceptible to autoimmunity, they also mount a limited anti-viral immune response compared to females 3 . For instance, males have a higher human cytomegalovirus (HCMV) burden after infection, suggesting increased susceptibility to viral threats 4 . This has also been recently illustrated with the COVID-19 pandemic, in which the strong male bias for severe disease has been postulated to reflect sex differences in immune responses 5 .…”

Predicting Post-treatment HIV Remission: Does Size of the Viral Reservoir Matter?

“…Ideally, the evolution of such a comprehensive molecular profile could allow the development of a personalized approach to HIV curative interventions. In particular, a gender-specific approach might be necessary, since several (but not all) studies demonstrated lower CA HIV RNA levels in women compared to men (Scully et al, 2019;Falcinelli et al, 2020;Gianella et al, 2020), and estrogen has been shown to repress HIV transcription (Das et al, 2018). Such approach should also include the personal medical history of each individual, namely the level of persistent immune activation despite ART, the history of comorbidities that is often associated with chronic inflammation, as well as current and historical ART regimens, all of which may contribute to the probability and timing of viral rebound.…”