The impact of point-of-care testing and treatment of sexually transmitted infections and bacterial V aginosis on the genital epithelial barrier integrity.

Abstract

In sub-Saharan Africa, women and young girls suffer the highest burden of HIV infections. Inflammation at the genital tract is a factor responsible for the increased susceptibility to HIV risk in women, presumably through related epithelial barrier damage and target cell recruitment. Considering the direct contribution of sexually transmitted infections (STIs) and bacterial vaginosis (BV) to this inflammation, their effective treatment could potentially reduce HIV risk in this vulnerable population. It has recently been shown in South African women that a point-of-care (POC) STI/BV detection model, immediate treatment, and expedited partner therapy (EPT) resolved STIs and reduced concentrations of genital proinflammatory cytokines. This study investigated an additional impact of the model on the genital epithelial barrier. Methods POC STI/BV screening was conducted on HIV-negative women (n=238) enrolled in the CAPRISA 083 trial between May 2016 and June 2017. Chlamydia trachomatis and Neisseria gonorrhoeae infections were detected by Xpert CT/NG test, while the OSOM Rapid test detected Trichomonas vaginalis. Women were further tested for Mycoplasma genitalium and BV using PCR and microscopy, respectively. Multiplex ELISA was used to quantify 48 cytokines and five matrix metalloproteinase (MMP) biomarkers of epithelial barrier integrity from menstrual cup (MC) specimens (MMP-1, MMP-2, MMP-7, MMP-9, MMP-10). Mann- Whitney U tests were used to assess the relationship between MMPs and STI/BV at baseline, with ANOVA and multivariable linear mixed models used to determine the impact of treatment on MMP concentrations. Results At baseline, women diagnosed with STI/BV (170/238) had higher concentrations of all MMPs compared to women with neither STI/BV (68/238; p>0.05). Several proinflammatory and chemotactic cytokine concentrations correlated significantly with that of MMPs at baseline. By 12 weeks post-treatment, 31/35 (88.57%) women resolved their baseline STIs, while only 14/57 (24.56%) resolved their baseline BV status. Most participants received concurrent treatment for STIs and BV (n=60), with few receiving treatments for STI (n=3) or BV alone15 (n=25). Significant reductions in MMP-1 concentrations were observed after 6 weeks in women treated for STI and BV (2.763 pg/ml; p= 0.0066) or STIs regardless of BV status (2.760 pg/ml; p= 0.0048). No changes in MMP concentrations were observed in women treated for BV. Conclusion POC STI/BV treatment was associated with a reduction in MMP-1 concentrations. This implies that although POC STI/BV treatment may treat STIs and reduce inflammation, the integrity of the genital epithelial barrier may not be fully restored, and women remain susceptible to genital infections, including HIV, as a result. Additional strategies may be needed to repair the genital epithelium after treatment.