Delineating the effect of sex hormone intake on immunity in cis and trans women with HIV

Background Although sex hormones are recognized to induce immune variations, little is known on the effect of exogenous sex hormone intake on immune responses in cis and trans women. Here, we aimed at quantifying how sex hormone intake affects HIV-1 immune markers in cis women (CW) and trans women (TW) with HIV. Methods We considered measurements of key HIV-1 immune markers (CD4, CD8, lymphocyte counts, and CD4:CD8 ratio) from cis men (CM), CW, and TW enrolled in the Swiss HIV Cohort Study. We modeled immune markers using linear mixed-effects models with an interaction between the variables “group” (CW, TW) and “with sex hormone intake” (yes/no). We conducted serum proteomics measurements of 92 inflammation markers on samples from 31 TW before and after sex hormone intake to assess the inflammation environment. Results We included 54’141 measurements from 3’092 CW and 83 TW sampled between 2015 and 2022, and 147’298 from 8’611 CM. Sex hormone intake was associated with significant distinct effects on CD4 and CD4:CD8 ratio between the different groups of women (p=0.0025 and 0.015). TW with sex hormone intake had significantly higher CD4 counts (median = 772 (1Q-3Q=520-1’006)) than without (median = 617 (1Q-3Q=426-892)). This increase was similar in magnitude to the difference in CD4 counts between CW and CM. None of the serum inflammation proteins showed significant concentration difference before and after sex hormone intake in TW. Conclusion This study highlights the need to consider the potential role of sex hormone intake in modulating the immune system among other biological and social factors, especially in TW in HIV.