Shanmugasundaram U, Critchfield JW, Giudice LC, et al. - Researchers sought to ascertain the effects of HIV on the female reproductive tract (FRT) via examining CD4+ T‐cell frequency, phenotype, and HIV‐specific T‐cell responses in the endocervix and endometrium of HIV‐infected women. In addition, comparison was performed of these tissues to the gastrointestinal tract (GIT). Eighteen women provided mucosal samples and blood; of these women, 4 were HIV positive and not on cART for at least 3 years prior to sampling, including 2 natural controllers (viral load [VL] undetectable and CD4 > 350); 9 women on cART with low to undetectable VL; and 5 HIV‐uninfected women. Following cART, endometrium continuously exhibited significantly elevated T‐cell activation, measured by CD38/HLA‐DR co‐expression, but T‐cell activation was lower in gastrointestinal tissues. They identified HIV‐specific CD8+ T‐cell responses in ileum, colon and endometrial tissues of women both on and off cART, and those not on cART exhibited these in higher magnitude. Findings thereby suggest that CD4+ T‐cell frequencies, immune activation and HIV‐specific T‐cell responses differ between the gastrointestinal and reproductive tracts, and highlight that HIV controllers differ from women on cART.