Systemic, Mucosal Immune Activation and Psycho-Sexual Health in ART-Suppressed Women Living with HIV: Evaluating Biomarkers and Environmental Stimuli

Abstract

Gender medicine is now an approach that can no longer be neglected and must be considered in scientific research. We investigated the systemic and mucosal immune response in a population of women living with HIV (WLWH) who were receiving successful ART and the sexual and psychological repercussions of HIV infection on the women's health. As control group, healthy women (HW) matched for age and sex distribution, without any therapy, were included. In summary, our study highlighted the persistence of immune-inflammatory activation in our population, despite virological suppression and a normal CD4 cell count. We found a hyperactivation of the systemic monocyte and an increase in inflammatory cytokine concentrations at the systemic level. The analysis carried out showed a significantly higher risk of HPV coinfection in WLWH compared to HW. Furthermore, our data revealed that WLWH have a profile compatible with sexual dysfunction and generalized anxiety disorders. Our study underlines that patients living with HIV should be evaluated by multidisciplinary teams. These findings also support the idea that more and different immunological markers, in addition to those already used in clinical practice, are needed. Further studies should be carried out to clarify which of these could represent future therapy targets.

Keywords: ART; FSFI; GAD test; HW; WLWH; cytokines; genital tract; mucosal immune response.

Figure 1

Concentration of proinflammatory biomarkers in WLWH and HW in plasma (A) and vaginal lavage (B). The differences between the two groups were evaluated using the nonparametric Mann–Whitney test. Data are shown as median (boxplots). Statistical significance (p) is reported in the graphics. *** p < 0.001; ** p < 0.01; * p < 0.05.

Figure 2

Quantitative dosage of anti CMV-IgG levels in WLWH and HW. The differences were evaluated using the nonparametric Mann–Whitney test. Data are shown as median (lines). Statistical significance (p) is reported in the graphics. **** p < 0.0001.

Figure 3

Screening for HPV in WLWH and HW. (A) The differences between the two groups were evaluated using the nonparametric Mann–Whitney test. Statistical significance (p) is reported in the graphics. * p < 0.05. (B) Different genotypes of HPV found in the study population (WLWH and HW).

Figure 4

Estimation of sexual hormones in WLWH and HW. The differences between the two groups were evaluated using the nonparametric Mann–Whitney test. Data are shown as median (box plots). Statistical significance (p) is reported in the graphics. * p < 0.05.

Figure 5

Sexual health and psychological well-being of the study population (A) Differences in overall FSFI scores in WLWH and HW. (B) Generalized anxiety disorder in WLWH and HW. Statistical significance (p) is reported in the graphics. * p < 0.05.

Figure 6

Representation of inflammatory, immunological, and sexual health markers: (CD4/CD8 ratio = cells/mm3; CD4+ = cells/mm3; NK cells = cells/mm3; sCD163 = soluble CD163; ng/mL; IL-6 = interleukin-6; pg/mL; IL-1beta = interleukin-1 beta; pg/mL IL-8 = interleukin-8 pg/mL; anti-CMV igG = IU/mL; testosterone; progesterone; FSFI) in plasma and vaginal lavage are represented by radar chart. Results are reported as estimated average variations. Radar plots were constructed scaling all variables in a range from 0% to 100% and plotting averages in WLWH and HW.

Figure 7

Correlations. (A) Positive correlation between CxCl10 and estradiol levels (r = 0.5, p = 0.01) in WLWH. (B) Positive correlation between FSFI and testosterone levels (r = 0.56, p = 0.02) in WLWH. (C) Positive correlation between FSFI and estradiol levels (r = 0.51, p = 0.02) in WLWH. (D) Negative correlation between FSFI and anxiety (Z-index) (r = −0.49, p = 0.03) in WLWH. (E) Negative correlation between years of HIV diagnosis and FSFI in WLWH (r = −0.43, p = 0.05). (F) Positive correlation between plasmatic sCD163 and estradiol levels (r = 0.3, p = 0.05) in HW. (G) Negative correlation between the age of the individuals and testosterone levels (r = −0.5, p = 0.01) in HW. All correlations were performed using the Spearman test. * p < 0.05.