Background
Doxycycline pre-exposure prophylaxis (doxyPrEP) has shown potential in preventing bacterial sexually transmitted infections (STIs) in gay, bisexual and other men who have sex with men (GBM). However, its impact on the microbiome is unknown. This study assessed rectal microbiome changes over 48 weeks in participants on HIV PrEP enrolled in a doxyPrEP trial.
Methods
The Dual Daily HIV and STI PrEP (DuDHS) study is an open-label, randomized pilot trial comparing immediate versus deferred doxycline (doxy) (100 mg daily) in HIV-negative GBM and transgender women on tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV PrEP. Fifty-two participants with a syphilis diagnosis within the past three years were recruited in Vancouver, Canada. All participants received 48 weeks of TDF/FTC for HIV PrEP, and were randomized 1:1 to the immediate (imm.) doxy arm (100 mg PO daily started immediately and continued to week 48) or the deferred (def.) arm (100 mg PO daily starting at week 24, continued to week 48). Rectal swabs for microbiome analysis were collected at baseline (BL), week 24, and week 48 and analyzed by 16S rRNA sequencing. Microbiome changes were evaluated using Wilcoxon signed rank and Mann-Whitney U tests, with p-values adjusted for multiple comparisons (FDR=5%).
Results
Among 311 operational taxonomic units (OTUs), the most prevalent were Finegoldia, Prevotella, Corynebacterium, and Streptococcus. At baseline, alpha diversity (Shannon’s H mean: imm: 2.58, def: 2.60, p=0.91), beta diversity (Bray-Curtis), and taxa composition were similar (p>0.05). No significant changes in alpha or beta diversity at the genus and family levels were observed between baseline, week 24, and week 48 (p>0.05). However, a slight decrease in alpha diversity at the order, class, and phylum levels was noted at week 48 in the immediate arm (mean: 0.84 vs. 0.66 at Phylum, p<0.05), but not in the deferred arm. Fusobacterium abundance showed a minor decrease at weeks 24 and 48 in both arms (mean difference from BL: 0.017 and 0.019 for imm. arm, 0.003 and 0.00005 for def arm, p<0.05), although this finding did not pass multiple hypothesis testing. Beta diversity remained similar between groups at weeks 24 and 48 (p>0.05)
Conclusions
This study is the first to assess microbiome changes due to doxyPrEP, showing minimal impact over 12 months. Further research is needed to explore the impact of doxycycline for STI prevention on microbiome function and antimicrobial resistance.