CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

diversity or composition of the microbiota. Shannon index and the relative abundance of Bacteroides and Prevotella before study product start were not associated with any drug level in secretions, biopsies, or blood at day 8. Conclusion: Application of hyperosmolar lubricant to the RM favors the relative abundance of Prevotella over Bacteroides and likely contributes to the enrichment for Prevotella among MSM reported previously. However, the diversity and composition of the RMmicrobiota do not appear to affect TFV and FTC levels in blood or RM tissues with oral dosing. Future research will be necessary to elucidate other contributing mechanisms for shifts in the microbiota, such as enema use, and whether other clinically relevant prevention outcomes are affected, such as RM susceptibility to HIV infection.

hypothesis testing correction. Although there was minimal (4.4%) overlap in proteins associated with rectal gel use between genders, pathway analysis identified activation of leukocyte recruitment pathways in both arms (Z>2.4, P<0.05). Oral tablet use was associated with trending protein alterations in males (226 (9.2%)), including factors involved in the activation of myeloid cells (Z=2.65, P=1.9E-4) and lymphocyte migration (Z=2.61, P=5.86E-8). Oral and vaginal formulations did not influence rectal protein expression in women. Microbial proteome analysis was overshadowed by high levels of Xanthamonas proteins, which was linked physician sampling gel that contained xantham, precluding microbiome comparisons. Conclusion: Oral and vaginal MVC use in women did not demonstrate an impact on rectal proteome expression in this study. Gender-specific trends were observed with rectal MVC gel use in all participants, oral tablet use in males, and suggested alterations in proteins involved in innate inflammatory processes. These findings suggest MVC topical gel use should be monitored in future safety trials and that gender differences in drug-host interactions may exist, warranting further study. 1057 MICROBIOME AND PROTEOME ALTERATIONS WITH DAPIVIRINE RING USE IN ADOLESCENT GIRLS Christina Farr Zuend 1 , Laura Noël-Romas 1 , Jeanne Marrazzo 2 , Sharon L. Hillier 3 , Charlene S. Dezzutti 3 , Kathleen E. Squires 4 , Katherine Bunge 3 , Adam Burgener 1 1 University of Manitoba, Winnipeg, MB, Canada, 2 University of Alabama at Birmingham, Birmingham, AL, USA, 3 University of Pittsburgh, Pittsburgh, PA, USA, 4 Thomas Jefferson University, Philadelphia, PA, USA Background: The antiretroviral-based dapivirine-containing vaginal ring has been shown to be effective at reducing HIV-1 acquisition, however, limited data exist on the impact of these products on the vaginal microbiome and mucosal environment in adolescents, a high risk group for HIV acquisition. Here we assessed host proteome and microbiome changes with dapivirine ring use in adolescent women enrolled in the MTN-023 trial using a comprehensive metaproteomics approach. Methods: MTN-023 was a Phase 2a randomized, double-blind placebo- controlled trial assessing the safety of a dapivirine vaginal ring in 96 U.S. women, ages 15-17. Participants were randomized 3:1 to a dapivirine or placebo ring to be inserted monthly for 6 months. Cervicovaginal lavage samples were collected monthly and a subset of longitudinal samples from 35 participants were analyzed for host and microbial proteome alterations by mass spectrometry. Differential protein expression was analyzed using t tests, IPA software and hierarchical clustering, and microbial taxa differences by Mann- Whitney U-test. Results: A total of 2046 bacterial proteins were identified belonging to 13 unique genera. Overall, the majority (82%) of the women had a microbiome dominated by Lactobacillus species, while 12%were Gardnerella dominant, and 6%were dominated by other anaerobic bacteria. In paired analysis the levels of L. crispatus increased over time in the trial (p=0.0007) while L. iners decreased (p=0.0003), and this did not differ by study arm. The 405 human proteins identified belonged to many functional pathways including innate immunity, inflammation, barrier function, and leukocyte recruitment. When stratified by study arm, 14 (3.5%) and 29 (7.2%) human proteins were differentially abundant (p<0.05) between baseline and follow-up in the placebo arm and dapivirine arms, respectively, but none passed multiple comparison correction. Interestingly, lack of condom usage in the last 30 days was linked to increases in neutrophil associated factors including PERM, MMP8, and ELNE. Changes in neutrophil factors were also associated with vaginal sex and Lactobacillus dominant microbiome (p<0.0001). Conclusion: Dapivirine ring use in adolescents was not associated with changes to the mucosal proteome or microbiome. During the 6 months of ring use, L. crispatus increased, which may reflect behavioral changes during protocol participation. These data support the mucosal safety profile of dapivirine vaginal ring in adolescents. 1058 ACTIVITY OF GRIFFITHSIN-M78Q-AN HIV ENTRY INHIBITOR-IN THE RECTAL ENVIRONMENT Henry Nabeta 1 , Sanet Steyn 1 , Amanda Lasnik 1 , Ian McGowan 2 , Joshua Fuqua 1 , Joseph C. Kouokam 1 , Kenneth E. Palmer 1 1 University of Louisville, Louisville, Kentucky, USA, 2 University of Pittsburgh, Pittsburgh, Pennsylvania, USA

Poster Abstracts

1056 GENDER-SPECIFIC RECTAL PROTEOME CHANGES WITH ORAL AND TOPICAL MARAVIROC USE AS PrEP Sarah Mutch 1 , Laura Noël-Romas 1 , Jarret C. Engstrom 2 , Rhonda M. Brand 3 , Aaron Siegel 2 , Ross Cranston 3 , Ian McGowan 3 , Adam Burgener 1 1 University of Manitoba, Winnipeg, MB, Canada, 2 Magee–Womens Research Institute, Pittsburgh, PA, USA, 3 University of Pittsburgh, Pittsburgh, PA, USA Background: Maraviroc (MVC) is an antiretroviral drug used in HIV therapy and is being explored for use in pre-exposure prophylaxis (PrEP); however, limited mucosal safety data exists on its use. Here we utilized a proteomics approach to study rectal mucosal immune changes in individuals using MVC in oral tablet, rectal gel or vaginal gel form in the CHARM-03 trial. Methods: CHARM-03 is a Phase 1 randomized, open label, crossover trial of the CCR5 inhibitor, MVC. The drug was administered as a 300mg oral tablet, 1% rectal gel and vaginal gel (N=18; 10 males, 8 females). Rectal tissue samples, taken prior to administration and 2 hours after the 8th and final dose, were analyzed by label-free mass spectrometry (MS). Intrapersonal changes in protein expression associated with drug use were analyzed by paired t-tests and considered trending at P<0.05, and significant at an FDR=5%. IPA software was used to annotate protein functions. Results: A total of 2447 human proteins and 179 bacterial proteins across 9 genera were detected by MS. Differential expression analysis identified the largest proteome alterations in participants using rectal gel (241 (9.8%) and 182 (7.4%) proteins in males and females, respectively); but none passed multiple

CROI 2018 405

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