The rectal mucosa and condomless receptive anal intercourse in HIV-negative MSM: implications for HIV transmission and prevention

Abstract

Most HIV transmissions among men who have sex with men (MSM), the group that accounted for 67% of new US infections in 2014, occur via exposure to the rectal mucosa. However, it is unclear how the act of condomless receptive anal intercourse (CRAI) may alter the mucosal immune environment in HIV negative MSM. Here, we performed a comprehensive characterization of the rectal mucosal immune environment for the phenotype and production of pro-inflammatory cytokines by CD4 and CD8 T cells, global transcriptomic analyses, and the composition of microbiota in HIV negative MSM. Our results show that compared to men who had never engaged in anal intercourse, the rectal mucosa of MSM engaging in CRAI has a distinct phenotype characterized by higher levels of Th17 cells, greater CD8+ T cell proliferation and production of pro-inflammatory cytokines, molecular signatures associated with mucosal injury and repair likely mediated by innate immune cells, and a microbiota enriched for the Prevotellaceae family. These data provide a high-resolution model of the immunological, molecular, and microbiological perturbations induced by CRAI, will have direct utility in understanding rectal HIV transmission among MSM, and will enhance the design of future biomedical prevention interventions, including candidate HIV vaccines.

Brief Report: Inflammatory Colonic Innate Lymphoid Cells Are Increased During Untreated HIV-1 Infection and Associated With Markers of Gut Dysbiosis and Mucosal Immune Activation

“…The study was not powered to address alterations in numbers of colonic cytokine-producing ILCs in the setting of HIV-1 infection. The two study groups were not matched for sexual practice, which has recently been reported to impact the intestinal microbiome independent of HIV-1 infection 49,50 and may drive mucosal immune cell activation and inflammation 50 and therefore be a contributing factor to our current observations. Enumeration of the specific ILC subsets was based on criteria used to identify NK22 cells 16 .…”

Fecal Bacterial Communities in treated HIV infected individuals on two antiretroviral regimens

“…First, we lack data on the sexual preference of our control group that is needed to assess the impact of HIV on the gut microbiome while controlling for sexual behavior. Interestingly, Prevotellaceae enrichment was found in most but not all MSM who engaged in CRAI19 suggesting that the factors driving Prevotella -rich microbiotas in MSM population are still unclear. In the light of recent publications1619, we are actively recruiting HIV-negative MSM to characterize their fecal microbiome and continue our research goal, which is to truly understand changes in the gut microbiome that are driven by HIV.…”

“…Interestingly, Prevotellaceae enrichment was found in most but not all MSM who engaged in CRAI19 suggesting that the factors driving Prevotella -rich microbiotas in MSM population are still unclear. In the light of recent publications1619, we are actively recruiting HIV-negative MSM to characterize their fecal microbiome and continue our research goal, which is to truly understand changes in the gut microbiome that are driven by HIV. Also, the number of HIV SN individuals is relatively small and should be increased to fully characterize the baseline microbiome of HIV-uninfected individuals in Mexico.…”

“…However, high Prevotella and low Bacteroides were associated with men who have sex with men (MSM) behavior independent of HIV status16 indicating that many previous studies may have not used proper control populations for elucidating differences driven by HIV. A recent paper also showed enrichment for the Prevotellaceae family in the rectal mucosa of HIV-negative MSM engaging in condomless receptive anal intercourse (CRAI) compared to individuals who never engaged in anal intercourse19. Also relatively high Prevotella and Bacteroides have previously been described to be indicators of enterotypes found in the human gut of populations in Europe2021 and the majority of individuals in both the US and Europe are dominated by Bacteroides-rich/Prevotella-poor microbiomes, whereas high Prevotella is common in agrarian cultures in the developing world2223.…”

On-demand microbicide products: design matters

“…Moreover, the T cells localized in the rectum are activated and express increased CCR5, a coreceptor used by HIV-1 for cell attachment. A recent study showed that MSM who engage in condomless RAI had a change in the activation status of immune cells [29]. Additionally, a marked change in the anorectal microbiota to a species ( Prevotella ) that could increase HIV transmission by increasing inflammation was also observed.…”