Impact of the griffithsin anti-HIV microbicide and placebo gels on the rectal mucosal proteome and microbiome in non-human primates.
Lauren GirardKenzie BirseJohanna B HolmPawel GajerMike S HumphrysDavid GarberPatricia GuenthnerLaura Noël-RomasMax AbouStuart McCorristerGarrett WestmacottLin WangLisa C RohanNobuyuki MatobaJanet McNichollKenneth E PalmerJacques RavelAdam D BurgenerPublished in: Scientific reports (2018)
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.
Keyphrases
- placebo controlled
- double blind
- phase iii
- rectal cancer
- label free
- antiretroviral therapy
- clinical trial
- hiv positive
- immune response
- hiv testing
- men who have sex with men
- hiv infected
- human immunodeficiency virus
- ms ms
- hepatitis c virus
- open label
- phase ii
- hiv aids
- endothelial cells
- ulcerative colitis
- wound healing
- study protocol
- healthcare
- primary care
- microbial community
- oxidative stress
- phase ii study
- radiation therapy
- gene expression
- transcription factor
- genome wide
- single cell
- high grade
- squamous cell carcinoma
- protein protein
- binding protein
- quality improvement
- simultaneous determination
- induced pluripotent stem cells