Cervical Inflammation and Immunity Associated With Hormonal Contraception, Pregnancy, and HIV-1 Seroconversion

Abstract

HC use, pregnancy, and young age alter cervical immunity in different ways known to increase risk of HIV, for example, through increased levels of pro-inflammatory cytokines or decreased levels of SLPI. Higher levels of RANTES may be one factor underlying a possible association between DMPA use and risk of HIV acquisition.

Cross-Sectional Analysis of Selected Genital Tract Immunological Markers and Molecular Vaginal Microbiota in Sub-Saharan African Women, with Relevance to HIV Risk and Prevention

“…Pregnant women (up to 14 weeks gestational age) were found to have increased levels of the proinflammatory cytokine IL-1␣ compared to the reference group of low-risk HIV-negative women. A recent study of Ugandan and Zimbabwean women found higher cervical levels of IL-1␤, IL-6, IL-8, VEGF, SLPI, and IL-1RA and lower IL-1RA/IL-1␤ ratios in pregnant versus nonpregnant HIV negative women (19). Kenyan pregnant women in our study showed lower levels of elafin.…”

The Human Microbiome during Bacterial Vaginosis

“…The proinflammatory cytokines and chemokines, whose levels are increased by BV-associated bacteria in vitro, and which are associated with BV in vivo, e.g., IL-1␤ and IL-8, enhance the risk of HIV transmission by directly stimulating HIV replication in latent viral reservoirs and by facilitating the trafficking and activation of CD4-positive host cells, which are normally sparse in the cervicovaginal mucosa (138). The reduction in the levels of antiviral factors by BV, e.g., SLPI, has also been associated with a higher risk of HIV acquisition (71), and women with BV have shown lower innate anti-HIV activity of their cervicovaginal secretions than controls (65).…”

“…Fichorova et al used a primary G. vaginalis isolate obtained from a woman with BV and showed that it caused upregulation of IL-8, RANTES, and soluble leukocyte protease inhibitor (SLPI) (70). The upregulation of RANTES is of particular significance since increased cervical levels of RANTES have been identified as the single most predictive marker of increased risk of HIV seroconversion in the sub-Saharan epicenter of the AIDS epidemics (71). Importantly, the pro-inflammatory activity of G. vaginalis was synergistically enhanced by coinfection with the protozoan parasite T. vaginalis, the most frequent companion of BV, and especially in the presence of Trichomonas vaginalis virus 1-4 species of the genus Trichomonasvirus, which are carried by this parasite (70).…”

Anatomic and Hormonal Changes in the Female Reproductive Tract Immune Environment during the Life Cycle: Implications for HIV/STI Prevention Research

“…Recent data suggest that hormonal contraception may alter cervical immunity via increased levels of pro-inflammatory cytokines, including RANTES, or decreased levels of secretory leukocyte protease inhibitor (SLPI). 62 The thinning of the vaginal epithelium is a known effect of natural progesterone during the luteal phase of the normal menstrual cycle. Although studies using a rhesus macaques model have shown that subcutaneous progesterone administration by implants resulted in vaginal epithelial thinning and increased simian immunodeficiency virus vaginal transmission, studies using human vaginal biopsies have generally not shown an association between hormonal contraception and significant changes in vaginal epithelial thickness and the number of cell layers from biopsy, Langerhans' cell count, or maturation index.…”