| 1. |
- Birse, Kenzie D., et al.
(author)
-
Genital Injury Signatures and Microbiome Alterations Associated With Depot Medroxyprogesterone Acetate Usage and Intravaginal Drying Practices
- 2017
-
In: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 215:4, s. 590-598
-
Journal article (peer-reviewed)abstract
- Background. Increasing evidence suggests depot medroxyprogesterone acetate (DMPA) and intravaginal practices may be associated with human immunodeficiency virus (HIV-1) infection risk; however, the mechanisms are not fully understood. This study evaluated the effect of DMPA and intravaginal practices on the genital proteome and microbiome to gain mechanistic insights. Methods. Cervicovaginal secretions from 86 Kenyan women, including self-reported DMPA users (n = 23), nonhormonal contraceptive users (n = 63), and women who practice vaginal drying (n = 46), were analyzed using tandem-mass spectrometry. Results. We identified 473 human and 486 bacterial proteins from 18 different genera. Depot medroxyprogesterone acetate use associated with increased hemoglobin and immune activation (HBD, HBB, IL36G), and decreased epithelial repair proteins (TFF3, F11R). Vaginal drying associated with increased hemoglobin and decreased phagocytosis factors (AZU1, MYH9, PLAUR). Injury signatures were exacerbated in DMPA users who also practiced vaginal drying. More diverse (H index: 0.71 vs 0.45; P =.009) bacterial communities containing Gardnerella vaginalis associated with vaginal drying, whereas DMPA showed no significant association with community composition or diversity. Conclusions. These findings provide new insights into the impact of DMPA and vaginal drying on mucosal barriers. Future investigations are needed to confirm their relationship with HIV risk in women.
|
|
| 2. |
- Bosire, Rose
(author)
-
Maternal antibody transfer in HIV-1 infected women and impact on infant health : the role of antiretroviral prophylaxis and breastfeeding practices
- 2019
-
Doctoral thesis (other academic/artistic)abstract
- Children born to human immunodeficiency virus type 1 (HIV-1) infected women are more vulnerable to infections and are more likely to die even when they are not HIV-1 infected. These adverse outcomes may blunt any gains made in escaping HIV-1 infection and could be ameliorated by improving maternal antibody transfer to the baby. The overall aim of this thesis was to study the role of antiretroviral prophylaxis and breastfeeding practices on maternal antibody transfer to their children and on the morbidity these children experience in the first year of life. Studies I and II examined the influence of antiretroviral treatment on antibody levels during pregnancy and delivery, in cord blood and breast milk. We used data from a randomized clinical trial in which HIV-1 infected pregnant women with CD4 counts between 200 and 500 were randomized to short-course zidovudine (ZDV) or triple antiretroviral therapy (ART) during pregnancy for prevention of HIV-1 transmission from mother to child. Antibody levels against measles, pneumococcus and rotavirus were measured in maternal plasma, infant cord blood and breast milk and compared between the trial arms. We found that maternal levels in plasma (Study I) and breast milk (Study II) were comparable between the two groups. Compared to women on short-course ZDV, women on triple ART transferred higher amounts of antibody via the placenta. In Study III, we compared infant morbidity, hospitalization, and mortality during the first year of life of HIV-1 exposed uninfected (HEU) children born to the women in Study I and II. Our morbidity outcomes of interest were those that cause significant mortality in these children namely diarrhea, pneumonia, and lower respiratory tract infection, and a composite measure of any infectious morbidity. We found important predictors for mortality in these children; however, we found no effect of the mother’s ART treatment regimen for any of these outcomes. Study IV used a real world setting in which HIV-1 infected women were enrolled during pregnancy into a clinic-level, before-after breastfeeding counseling intervention study. Women in the intervention arm were offered three counseling sessions that promoted exclusive breastfeeding (EBF), explained breastfeeding techniques and described its benefits. EBF prevalence was comparable between the two arms at 14 weeks postpartum. We found no differences between the groups for 6-week HIV-free survival or 14-week infant survival for the children born to these women. The results of this thesis show some benefit for maternal triple ART compared to short-course ZDV in passive antibody transfer via the placenta and that high EBF rates are attainable. The non-significant findings for impact on morbidity and mortality outcomes among HEU children highlight the complexity of unravelling the mechanisms that underlie the higher vulnerability that has been observed in these children. The findings from this thesis may be used to inform the design of future studies so that ultimately the health and survival of HEU children can be secured.
|
|
| 3. |
- Häggmark, Anna, 1985-, et al.
(author)
-
A High-throughput Bead-based Affinity Assay Enables Analysis of Genital Protein Signatures in Women At Risk of HIV Infection
- 2019
-
In: Molecular & Cellular Proteomics. - : AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. - 1535-9476 .- 1535-9484. ; 18:3, s. 461-476
-
Journal article (peer-reviewed)abstract
- Women at high risk of HIV infection, including sex workers and those with active genital inflammation, have molecular signatures of immune activation and epithelial barrier remodeling in samples of their genital mucosa. These alterations in the local immunological milieu are likely to impact HIV susceptibility. We here analyze host genital protein signatures in HIV uninfected women, with high frequency of condom use, living in HIV-serodiscordant relationships. Cervicovaginal secretions from women living in HIV-serodiscordant relationships (n = 62) were collected at three time points over 12 months. Women living in HIV-negative seroconcordant relationships (controls, n = 25) were sampled at one time point. All study subjects were examined for demographic parameters associated with susceptibility to HIV infection. The cervicovaginal samples were analyzed using a high-throughput bead-based affinity assay. Proteins involved in epithelial barrier function and inflammation were increased in HIV-serodiscordant women. By combining several methods of analysis, a total of five proteins (CAPG, KLK10, SPRR3, elafin/PI3, CSTB) were consistently associated with this study group. Proteins analyzed using the affinity set-up were further validated by label-free tandem mass spectrometry in a partially overlapping cohort with concordant results. Women living in HIV-serodiscordant relationships thus had elevated levels of proteins involved in epithelial barrier function and inflammation despite low prevalence of sexually transmitted infections and a high frequency of safe sex practices. The identified proteins are important markers to follow during assessment of mucosal HIV susceptibility factors and a high-throughput bead-based affinity set-up could be a suitable method for such evaluation.
|
|
