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It is well-known that transgender women are at increased risk for HIV . In fact, the Centers for Disease Control and Prevention (CDC) report that from 2009 to 2015, 2351 transgender individuals were diagnosed with the virus in the United States alone; 84% were transgender women.Although this increased risk of HIV infection has been attributed to behavioral risk factors in this population, in an oral abstract session at the 25th Conference on Retroviruses and Opportunistic Infections (CROI), Sandhya Vasan, MD, from the department of Retrovirology at the Armed Forces Research Institute of Medical Sciences (AFRIMS), in Bangkok, Thailand, shared that other factors may also impact the risk of infection, such as the effects that exogenous hormones have on the immune system and the impact that injectable fillers or sex reassignment surgery (SRS) has on immune reactivation.To investigate this further, Dr. Vasan and her team conducted a cross-sectional study in a group of 28 HIV-negative participants: 10 men who have sex with men (MSM), 10 natal or cis-women (CW), and 8 transgender women who had undergone SRS.Transgender participants were found to have had a higher median of sexual partners over the course of their lifetime compared with CW and MSM. The median number of sexual partners for transgender women was 53, whereas MSM had a median of 25 partners, and CW had a median of 3 partners.“Median time post SRS was 1.3 years, all by penile inversion, with 7 out of 8 still using dilators post SRS,” according to the authors. The researchers noted that all the transgender women enlisted in the study reported having participated in anal sexual intercourse, while 7 out of the 8 reported having participated in neovaginal sex.The mean age of gender dysphoria, or the condition of feeling one’s emotional and psychological identity as male or female to be opposite to one’s biological sex, in transgender women was 7 years; the mean age for cross-dressing was 13 years; hormone initiation was 14 years; and the mean age for SRS was at 24 years.Median duration of hormones in the transgender participants was found to be 7.6 years, with 5 out of the 8 participants reporting the use of estrogen/progesterone and 3 participants reporting the use of estrogen only.Peripheral blood mononuclear cells (PBMC) and mucosal mononuclear cells (MMC) were isolated from sigmoid biopsies conducted on participants from all 3 groups; furthermore, the investigators collected cervical swabs from the CW participants and neovaginal swabs from the transgender participants.No difference in the frequency of CD4+ or CD8+ T cells in PBMC and sigmoid MMC was found among the groups. The frequency of neovaginal CD4+ T cells was found to be decreased by 1.8% and neovaginal CD8+ T cells were increased by 77.7%, compared with the sigmoid and cervical CD4+ T cells—which were 54.4% and 48.3% respectively—and the sigmoid and cervical CD8+ T cells, which were 33.6% and 30.2% respectively.“Neovaginal CD4+CCR5+ T cell frequency was lower in the cervical MMC (1.2% vs. 35%, P = .02), but comparable to sigmoid MMC (31.1%, P = NS). Median fluorescent intensity of CD4+CCR5+ T cells was higher in neovaginal MMC (1491) vs. sigmoid MMC (761, P = .04), but similar to cervical MMC (578, P = NS),” the study authors wrote. “Increased activated CD4+ T cells (HLA-DR+/CD38+), were seen in cervical MMC (2.3%) vs. sigmoid (1.1%) and neovaginal MMC (1.0%, P = .02 and P = .05, respectively).”The investigators reported that filler use was found to be much higher in transgender women (63%), compared with MSM (10%) or CW (0%) and it was found that 1 transgender woman in particular who was using hip fillers had multiple inguinal siliconomas, which corresponded with a “high frequency of peripheral Ki67+CD4+ expression (0.4% vs. median 0.1% in transgender women) and Ki67+CD4+ cells in her inguinal lymph nodes.”The composition of CD4+ and CD8+ T cells of neovaginal MMC varied from sigmoid and cervical MMC. Furthermore, the investigators did not note an increased frequency of neovaginal-activated CD4+ or CD4+CCR5+ T cells.“Higher use of fillers in transgender women may contribute to systemic immune activation, although studies are ongoing,” the authors wrote. Characterizing the biologic risk factors associated with HIV that are specific to transgender women may be key to informing more effective preventive strategies.