Table 1.
Demographic and clinical characteristics of the participants included in the study.
Fig 1.
Peripheral blood immune cell subsets in YMSM with and without HIV and asymptomatic rectal STI.
Twenty-three innate and adaptive cell subsets from peripheral blood were analyzed by flow cytometry. (A) There was no significant separation between YMSM with and without asymptomatic STI as analyzed by PERMANOVA. Purple dots represent STI-positive YMSM; green triangles represent STI-negative YMSM. (B) Significant separation was seen between YMSM with and without HIV. Pink dots represent HIV-positive YMSM; teal triangles represent HIV-negative YMSM. (C) After adjusting for STI, linear decomposition modeling (LDM) identified four cell subsets that were significantly (FDR<5%) different between YMSM with and without HIV. Cell subset percentages were log transformed for analyses. HIVpos = YMSM with HIV; HIVneg = YMSM without HIV.
Fig 2.
Rectal mucosal immune cell subsets in YMSM with and without HIV and asymptomatic rectal STI.
Twenty-six innate and adaptive cell subsets from rectal mucosal tissues were analyzed by flow cytometry. (A) There was no significant separation between YMSM with and without asymptomatic STI as analyzed by PERMANOVA. Purple dots represent STI-positive YMSM; green triangles represent STI-negative YMSM. (B) Significant separation was seen between YMSM with and without HIV. Pink dots represent HIV-positive YMSM; teal triangles represent HIV-negative YMSM. (C) After adjusting for STI, LDM identified 17 cell subsets that were significantly (FDR<5%) different between YMSM with and without HIV. Cell subset percentages were log transformed for analyses. HIVpos = YMSM with HIV; HIVneg = YMSM without HIV.
Fig 3.
Rectal mucosal microbiome composition in YMSM with and without STI.
(A) Representative bar plot of the top 10 phyla identified by 16S rRNA sequencing from rectal mucosal specimens of the 86 participants with concordant clinical diagnostic assay and 16S microbiome sequencing STI results. (B) Representative bar plot of the top 10 genera identified by 16S rRNA sequencing from rectal mucosal specimens of the 86 participants with concordant clinical diagnostic assay and 16S microbiome sequencing STI results. (C) Bray-Curtis and (D) Jaccard measures of beta diversity, both measured by PERMANOVA, both demonstrated significant differences between the microbiome composition of YMSM with and without STI. Purple dots represent STI-positive YMSM; green dots represent STI-negative YMSM. (E & F) Presence-absence analyses identified 11 genera with a significantly different (FDR<10%) probability of presence between the two groups. STIpos = YMSM with asymptomatic rectal bacterial STI; STIneg = YMSM without asymptomatic rectal bacterial STI.
Fig 4.
Asymptomatic bacterial STI is associated with differential gene expression among YMSM with HIV only.
(A-D) Volcano plots of differentially expressed genes in the four study groups. Red dots indicate genes with significant (padj<0.1) differential expression. (E) List of 40 genes that were identified both as interaction genes and as differentially expressed among YMSM with HIV and rectal asymptomatic bacterial STI. STIpos = YMSM with asymptomatic bacterial STI; STIneg = YMSM without asymptomatic bacterial STI. HIVpos = YMSM with HIV; HIVneg = YMSM without HIV.
Fig 5.
Asymptomatic bacterial STI is associated with upregulation of transcriptomic pathways involved in inflammation and mucosal injury and repair among YMSM with HIV.
Gene set enrichment analyses were conducted using the (A) Hallmark gene set and (B) Reactome gene set. Red dots represent pathways that are upregulated and purple dots represent pathways that are downregulated. The size of the dot corresponds to the nominal p-value.
Fig 6.
There is no significant effect of asymptomatic rectal STI on HIV replication in blood or rectal tissues.
HIV viral loads in (A) plasma and (B) rectal tissues among YMSM with HIV. Orange circles represent YMSM with HIV and without STI. Red squares represent YMSM with HIV and with STI. (C) Plot of p24 concentrations from rectal explant challenge experiments among YMSM without HIV and not on oral PrEP. Green circles represent YMSM without HIV and without STI. Blue squares represent YMSM without HIV and with STI.