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CD4s in "Normal" Anal Mucosa Are Activated in HIV+
Men With Anal Cancer Precursor
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HIV Research for Prevention (HIVR4P), October 21-25, 2018, Madrid
Mark Mascolini
Antiretroviral-treated men with persistent HPV infection and high-grade anal intraepithelial neoplasia (HGAIN)--an anal cancer precursor--had more activated CD4 cells in normal-appearing anal mucosa than men without AIN [1]. University of Toronto researchers who conducted this study believe their findings show a need to investigate the impact of HGAIN on HIV susceptibility in HIV-negative men who have sex with men (MSM).
The Toronto team noted that prior work links several sexually transmitted infections to more HIV shedding and immune activation in mucosal tissue. Abundant research documents high rates of anal HPV infection in MSM. Although most of these infections resolve spontaneously, some persist and cause AIN. But little is known about the impact of HPV infection and AIN on mucosal HIV transmission. The Toronto team hypothesized that AIN in MSM taking antiretroviral therapy (ART) "is associated with increased density of activated CD4 T cells in the anorectal mucosa but not associated with increased frequency of anorectal HIV RNA detection."
Health workers collected anal swabs and anal biopsies from HIV-positive MSM on ART in Toronto. They biopsied AIN-free mucosa from all participants and AIN-affected areas from men with histologically confirmed AIN. Researchers isolated CD4 cells from biopsies and analyzed them for activation markers including CD38, HLA-DR, CCR5, and CCR6. They used RT-PCR to measure HIV levels in anal swabs collected by participants and physicians.
The analysis focused on 41 men, 14 without AIN, 13 with low-grade AIN (LGAIN), and 14 with HGAIN. Number of CD4 cells in mucosal tissue did not differ by AIN status. And HIV could not be detected more in HGAIN or LGAIN mucosal areas than in no-AIN tissue.
But men with HGAIN had significantly more CD4-cell activation (CD38/HLA-DR coexpression) in normal-appearing mucosa than did men with no AIN (median 8.80% versus 4.50%, P = 0.035). Activated CD4 cells appeared in both HGAIN-confirmed areas and neighboring normal areas.
The Toronto researchers believe this is the first study showing that CD4 cells in clinically normal-appearing anal mucosa of men with HGAIN are more activated than CD4s in anal mucosa of men without AIN. Although they also detected HIV RNA in anal mucosa of many of these antiretroviral-treated men, RNA levels were about 5-log (100,000-fold) lower than in antiretroviral-naive people "and are unlikely to be meaningful in terms of [HIV] transmission." But CD4-cell activation like this in antiretroviral-naive men with HIV and HGAIN "would be expected to increase HIV shedding and transmission."
Reference
1. Choi Y, Salit I, Sano M, et al. Association of persistent HPV infection with immune activation in the anorectal mucosa. HIV Research for Prevention (HIVR4P), October 21-25, 2018, Madrid. Abstract P18.21LB.
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