Genital Tract Leukocytes and Shedding of Genital HIV Type 1 RNA

Abstract

Background The mechanism of human immunodeficiency virus (HIV) transmission via heterosexual intercourse is unknown. We sought to determine whether the presence of inflammatory cells in the vagina is associated with the presence of genital tract HIV type 1 (HIV-1) RNA. Methods Analysis of a longitudinal prospective cohort was performed. Women with HIV-1 infection were assessed with use of paired plasma and cervicovaginal lavage specimens. Viral load measurements were performed using nucleic acid sequence—based amplification. White blood cells found in the genital tract (GT WBCs) were quantified using a hemacytometer. Common lower genital tract infections assessed for association with viral shedding (i.e., genital tract viral load [GTVL]) included bacterial vaginosis, candidiasis, and trichomoniasis. Generalized estimating equations were used to estimate the prevalence and odds of detectable GTVL by GT WBC. The association was examined both in the presence and in the absence of lower genital tract infections. Results A total of 97 women and 642 visits were included in the analysis. Median duration of follow-up was 30.4 months. Thirty women (31%) had detectable GTVL at any visit. The median CD4 cell count at baseline was 525 cells/μL. Most women were antiretroviral therapy naive at baseline. After adjustment for plasma viral load, the odds of detectable GTVL increased as GT WBC increased, with an odds ratio of 1.36 (95% confidence interval, 1.1–1.7) per 1000-cell increase in GT WBC among women without lower genital tract infections. After adjustment for plasma viral load and lower genital tract infections by incorporating them in a regression model, GT WBC remained significantly associated with GTVL, with an adjusted odds ratio of 1.22 (95% confidence interval, 1.08–1.37). Conclusions The presence of GT WBC is associated with an increased risk of detectable GTVL.

Elevated Cervical White Blood Cell Infiltrate Is Associated with Genital HIV Detection in a Longitudinal Cohort of Antiretroviral Therapy–Adherent Women

“…These data corroborate those of Anderson et al [33], which were derived from a cohort with mixed ART use by testing cervicovaginal lavage samples for extended follow-up periods. Higher concentrations of cervical cell infiltrates in HIV-infected women with local inflammation have been observed previously [26].…”

“…Cervical cell types were enumerated by microscopic examination using Endtz-trypan stain to differentiate epithelial cells, polymorphonuclear cells (PMNs), and mononuclear cells; to compute the total white blood cell (WBC) count; and to evaluate red blood cell (RBC) counts [39]. Cervical cells were enumerated from a suspension of cells eluted from the cytobrush, and у100 cells were counted, increasing the sensitivity of cell-type characterization, compared with 130 PMNs per high-powered field measures [8,40,41], similar to methods described by others [33]. Total WBC counts were enumerated in the vaginal mucosa by means of Gram-stained vaginal smears.…”

“…In both cross-sectional and longitudinal analyses of cohorts with varying ART use and/or adherence, genital cellular infiltrate has been associated with cervicovaginal HIV RNA detection [13,33]. These analyses were derived from testing of cervicovaginal lavage fluid, and it is unclear whether the cervix or the vagina was the site of cell trafficking.…”

Association between symptomatic vulvovaginal candidiasis and HIV RNA levels in plasma and genital secretions among women on HAART

“…[1][2][3] Conditions associated with genital inflammation, particularly genital ulcers, have been associated with HIV shedding in the GT. [4,5] While the association between non-ulcerative LGTIs such as bacterial vaginosis (BV) and GT HIV shedding has been well established, [6,7] current studies have shown a less welldefined relationship between vulvovaginal candidiasis (VVC) and HIV shedding. In addition to BV that is not an established sexually transmitted infection (STI), vaginitis , an STI caused by Trichomonas vaginalis, has also been shown to increase the risk of HIV acquisition among women, [8,9] and sexual and perinatal HIV transmission.…”

Associations between Virologic and Immunologic Dynamics in Blood and in the Male Genital Tract

“…Although HIV RNA levels in blood roughly correlate with levels in seminal plasma (13,39,56,69,72), local genital factors, particularly concomitant sexually transmitted infections (STI), can increase HIV shedding in semen (38,39,61). Common bacterial STI can also increase the number of immune cells in the genital tract (9,52), and elevated counts of white blood cells in semen are associated with higher seminal HIV shedding (3,4,69,80). Since HIV principally infects and replicates in CD4 ϩ T lymphocytes, monocytes, and macrophages (16,30), an accumulation of these cells in semen is likely to increase the risk of sexual HIV transmission (40,79).…”