| Publication Abstract Display | | Type: Published Abstract | | Title: Sex differences in CMV Replication and HIV Persistence during Suppressive ART. | | Authors: Gianella S, Tran S, Vargas M, Caballero G, Oliveira M, Lada S, Zhao M, Mathad J, Wilkin T | | Year: 2019 | | Publication: CROI | | Volume: Issue: Pages: | | Abstract:Background
CMV replication is common in men living with HIV (MLWH), and is associated with increased immune activation, T cell proliferation and larger HIV reservoirs. The prevalence of CMV shedding and its relationship to HIV persistence have not been investigated in women (W)LWH.
Methods
Fifty virologically suppressed WLWH were enrolled in New York City (between 07/2014 thru 09/ 2016). Participants provided oral, vaginal and urine samples with peripheral blood mononuclear cells (PBMCs, N=50) at one time-point. 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 generated from 49 CMV-seropositive MLWH (blood and semen) were used as controls (Gianella et al, PMID: 26842469).
Results
Median age was 53 years for women and 46 years for men; 28 (56%) women were post-menopausal and 43 (86%) acquired HIV through heterosexual contact. All men reported sex with men as risk factor. Both groups were chronically infected with HIV and had undetectable HIV RNA in blood. Median CD4+ were 721 cells/l (490-930) for women and 625 (538-744) for men.
Levels of cellular HIV DNA and unpliced HIV RNA were not different between sexes, but women were less likely to have detectable msHIV RNA (54% versus 100% in men, Fisher <0.01). Of the 49 CMV-seropositive WLWH, 16/49 (33%) had detectable CMV DNA in at least one specimen type, compared to 26/49 (53%) men (P<0.01), Table 1. CMV DNA was most frequenty detected in vaginal swabs (16%) and PBMCs (14%) for women and in semen (40%) for men. Unlike previously shown in men, the presence of CMV DNA was not associated with increased HIV DNA in women. Among women, pre-menopausal status was associated with significantly lower HIV DNA compared to post-menopause, after adjusting for age and duration of HIV infection (42 versus 150 HIV DNA copies/106 cells, P<0.01. Men: 90 copies/106 cells). There was no difference in cellular HIV RNA transcription and CMV shedding between pre- and post-menopausal women.
Discussion
WLWH co-infected with CMV presented reduced cellular HIV transcription and less subclinical CMV replication compared to men, but similar HIV DNA levels. Interestingly, post-menopausal status was independently associated with increased HIV DNA reservoir, even after adjusting for age and duration of HIV infection. The exact mechanism is unclear and could be evaluated in future longitudinal studies. |
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