Exciting recent data from our high quality clinical specimens reveal 2 phenotypes in 2 of the progestin groups. Specifically, compared to baseline mucus samples, Nuvaring shows an extreme phenotype by immobilizing HIV-1 transport in cervical mucus (CM). In contrast, the current DMPA results indicate an increase in virus transport in cervicovaginal mucus (CVM), consistent with an increase in virus transport observed in macaque systems. We believe these data validate the premise that contraceptive choice has a significant impact on mucosal environment and request leverage to our Aims that would require a modest increase in patient enrollment for mucus and associated immune analyses. Specifically we proposed: (i) To increase our Nuvaring patient group to n=25, gaining powering equivalency to LNG-IUS and DMPA groups (ii) To establish a third (6 month) visit from LNG-IUS patients based on clinical and preliminary mucus data that suggest changes in the concentration of progestin delivered by the IUS early (~1 month) and later (~6 months) after installation differentially impact upon the genital mucus barrier (iii) The extreme phenotype of the CM with Nuvaring begs questions relating to the underlying mechanism. This unique cohort of samples will allow us to conduct, an expanded comprehensive genome-wide transcriptional and cellular pathway analysis using next-generation sequencing (RNA-Seq) to identify differences in key cellular pathways in the tissue environment among the 3 contraceptive groups, with a special emphasis on the regulation and post-translational modification of mucins, inflammation and barrier function. Together these extremely timely and targeted studies will extend upon our novel findings to date and drill deeper to close gaps in our knowledge and understanding of the effect and safety of systemic and locally delivered progestins on HIV transmission in young women.
|Effective start/end date||7/1/15 → 6/30/17|
- Louisiana State University Health Sciences Center - New Orleans (16-17-103//R01AI110373)
- National Institute of Allergy and Infectious Diseases (16-17-103//R01AI110373)
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