High HIV infection rates in transgender women (TGW) are largely attributed to increased behavioral risk factors. However, effects of exogenous hormones on the immune system and injectable fillers or sex reassignment surgery (SRS) on immune activation may alter HIV risk.
A cross-sectional study of HIV negative volunteers including 10 MSM, 10 natal or cis-women (CW) and 8 TGW post SRS was conducted. Peripheral blood mononuclear cells (PBMC) and mucosal mononuclear cells (MMC) isolated from sigmoid biopsies (TGW, MSM, CW), and cervical (CW) and neovaginal (TGW) swabs were analyzed. Lymph node (LN) biopsies underwent immunohistochemical staining.
Median lifetime sexual partners was higher in TGW (53) vs. CW (3, p=0.006) and MSM (25, p=NS). Among TGW, mean age of initial gender dysphoria was 7yrs, cross dressing 13yrs, hormone initiation 14yrs, and SRS 24yrs. Median duration of hormone use in TGW was 7.6yrs, with 5/8 using estrogen/progesterone, and 3/8 estrogen only. Median time post SRS was 1.3yrs, all by penile inversion, with 7/8 still using dilators post SRS. All TGW reported anal sex; 7/8 reported neovaginal sex. No difference in frequency of CD4+ or CD8+ T cells in PBMC and sigmoid MMC among groups was found. Frequency of neovaginal CD4+ T cells was decreased (1.8%) and CD8+ T cells increased (77.7%) vs. sigmoid and cervical CD4+ (54.4% and 48.3%), and CD8+ (33.6% and 30.2%) T cells (p<0.001, all). Neovaginal CD4+CCR5+ T cell frequency was lower in than cervical MMC (1.2% vs 35%, p=0.02), but comparable to sigmoid MMC (31.1%, p=NS). MFI of CD4+CCR5+ T cells was higher in neovaginal MMC (1491) vs. sigmoid MMC (761, p=0.04), but similar to cervical MMC (578, p=NS). 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=0.02 and p=0.05, respectively). Filler use was higher in TGW (63%) than MSM (10%) or CW (0%). One TGW using hip fillers had multiple inguinal siliconomas, corresponding with high frequency of peripheral Ki67+CD4+ expression (0.4% vs median 0.1% in TGW) and Ki67+CD4+ cells in her inguinal LN.
CD4/CD8 T cell composition of neovaginal MMC differs from sigmoid and cervical MMC. There was no increase in frequency of neovaginal activated CD4+ or CD4+CCR5+ T cells. Higher use of fillers in TGW may contribute to systemic immune activation, although studies are ongoing. Characterization of biologic HIV risk factors specific to TGW may inform additional prevention strategies.