The biological basis for the variability in HIV risk is not fully understood. The microbiome has been shown to affect the immune milieu of the genital mucosa, and we have shown that penile anaerobes were significantly decreased by medical male circumcision, which also reduced HIV acquisition. Thus, we hypothesize that genital microbiota may affect host susceptibility to HIV via immune activation.
We conducted a case-control study using enrollment data from a male circumcision randomized trial in Rakai, Uganda. Cases (n=68) were men who acquired HIV during the 24-month follow-up and controls (n=199) were men who remained HIV-uninfected over the study period. Cases and controls were matched by randomization assignment. Real-time PCR and sequencing of the 16S rRNA V3V6 region of DNA extracted from eluent of sub-preputial swabs were used to estimate bacterial absolute abundance as the log[sub]10[/sub] 16S rRNA gene copies/swab. Logistic regression was used to assess the adjusted odds ratio (adjOR) of seroconversion associated with anaerobe abundance.
At enrollment, the cases had significantly higher abundance of penile anaerobes than controls, including Prevotella, Dialister, Finegoldia, and Peptostreptococcus. Higher abundance of penile anaerobes was associated with increased of HIV seroconversion (Table 1). The highest odds of HIV acquisition associated with each log10 increase in abundance were for Prevotella (adjOR=1.54, 95% CI: 1.22-1.98), Finegoldia (adjOR=1.50, 95% CI: 1.12-2.07), Peptoniphilus (adjOR=1.48, 95% CI: 1.13-1.99), and Dialister (adjOR=1.47, 95% CI: 1.20-1.84). Cases were more likely than the controls to have detectable levels of IL-8, MCP-1, MIG, and MIP-3α (≥ 2 cytokines, p = 0.06). Additionally, sub-preputial IL-8 levels correlated significantly with anaerobe abundance.
Penile anaerobes may play a role in HIV susceptibility in men comparable to bacterial vaginosis in women, suggesting the possibility that a sexually transmissible ecological imbalance increases HIV susceptibility in both sexes.