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Abstract
Topical microbicides are being explored as an HIV prevention method for individuals who practice receptive anal intercourse. In vivo studies of these microbicides are critical to confirm safety. Here, we evaluated the impact of a rectal microbicide containing the antiviral lectin, Griffithsin (GRFT), on the rectal mucosal proteome and microbiome. Using a randomized, crossover placebo-controlled design, six rhesus macaques received applications of hydroxyethylcellulose (HEC)- or carbopol-formulated 0.1% GRFT gels. Rectal mucosal samples were then evaluated by label-free tandem MS/MS and 16 S rRNA gene amplicon sequencing, for proteomics and microbiome analyses, respectively. Compared to placebo, GRFT gels were not associated with any significant changes to protein levels at any time point (FDR < 5%), but increased abundances of two common and beneficial microbial taxa after 24 hours were observed in HEC-GRFT gel (p < 2E-09). Compared to baseline, both placebo formulations were associated with alterations to proteins involved in proteolysis, activation of the immune response and inflammation after 2 hours (p < 0.0001), and increases in beneficial Faecalibacterium spp. after 24 hours in HEC placebo gel (p = 4.21E-15). This study supports the safety profile of 0.1% GRFT gel as an anti-HIV microbicide and demonstrates that current placebo formulations may associate with changes to rectal proteome and microbiota.
Highlights
Receptive anal intercourse (RAI) is a large contributing factor to new HIV infections globally
We evaluated the rectal mucosal proteome, as well as the composition and structure of the rectal microbiota associated with intra-rectal application of 0.1% GRFT gel, while comparing two different gel formulations, HEC and Carbopol, in a non-human primate (NHP) model
This study was performed to evaluate the effects of 0.1% GRFT gel on the rectal mucosal proteome and microbiome when formulated in either HEC or carbopol
Summary
Receptive anal intercourse (RAI) is a large contributing factor to new HIV infections globally. While the significance of these alterations with HIV acquisition risk and gel efficacy are currently unknown, efforts to develop safe rectal microbicide that do not impact the natural environment of the rectal mucosa are desirable. Another important consideration in the development of new microbicide products is the choice of gel formulation[27]. In contrast to RMP-02/MTN-006, MTN-007 used a gel product containing a reduced amount of glycerin This change in formulation was associated with fewer adverse events[30,31], demonstrating the importance of exploring multiple gel formulations in the development of rectal microbicide products
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