Bored again. Just checking into background publications that might pertain the new HIV study concerning TGW (Transgender Women) with elevated inflammation markers with HIV and using feminizing hormone treatment, progestogens, estrogens, and antiandrogens etc.
(Joke warning: when I tried to type “feminizing” my iPhone decided I meant “demonizing.” Now, that is the problem with World!!!)
But back to “elevated inflammation.”
From August 2023,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543719/
Distinct mucosal and systemic immunological characteristics in transgender women potentially relating to HIV acquisition
Good read. Seems this through line might be what Dr J is thinking of for our small trial in HIV patients in hormonal treatments with elevated inflammation, at least at the site of the neo-vagina, still looking for blood ID's.
Here’s a couple of quotes to pass the time.
“Transgender women (TGW) are disproportionally affected by HIV infection, with a global estimated prevalence of 19.9%, often attributed to behavioral risk factors, with less known about biological factors. We evaluated potential biological risk factors for HIV acquisition in TGW at the sites of viral entry by assessing immune parameters of the neovaginal surface and gut mucosa. The neovagina in TGW, compared with the vagina in cisgender women (CW), shows distinct cell composition and may pose a more inflammatory environment, evidenced by increased CD4+ T cell activation and higher levels of soluble markers of inflammation (C-reactive protein, soluble CD30). Increased inflammation may be driven by microbiome composition, as shown by a greater abundance of Prevotella and a higher Shannon Diversity Index. In addition, we have observed higher frequency of CD4+CCR5+ target cells and decreased DNA methylation of the CCR5 gene in the gut mucosa of TGW compared with CW and men who have sex with men, which was inversely correlated with testosterone levels. The rectal microbiome composition in TGW appears to favor a proinflammatory milieu as well as mucosal barrier disruption. Thus, it is possible that increased inflammation and higher frequencies of CCR5-expressing target cells at sites of mucosal viral entry may contribute to increased risk of HIV acquisition in TGW, with further validation in larger studies warranted.”
And furthermore,
“TGW undergo feminizing hormone treatment to increase female characteristics, which includes the usage of progestogens, estrogens, and antiandrogens (5). Recommended feminizing hormone regimens are composed of estrogen to promote female secondary sexual characteristics and androgen-lowering drugs to inhibit male secondary sexual characteristics by decreasing endogenous testosterone production or testosterone activity (6, 7). However, in Thailand, there is high use of feminizing hormone treatment reported outside the reference regimen as these drugs can be purchased without a medical prescription (
. Progesterone and estrogen are known to have differential effects on mucosal epithelial barriers, modulating cellular expression of CCR5, the primary co-receptor for entry of R5 tropic HIV into CD4+ T cells (9), and α4β7, a cellular gut-homing marker (10), as well as on vaginal epithelial thickness (11, 12). Sex hormone levels are also linked to inflammation, induced by the impact they have on the composition of microbial communities…”
Sorry in advance guys…please read on…
“Gender affirmation surgery (GAS) by vaginoplasty aims to create a functional vagina which can be achieved by a variety of surgical techniques including penile skin inversion, colonic flap, or peritoneal flap vaginoplasty (21, 22). Currently, penile skin inversion is the most widely used technique for GAS. The cell composition of the skin creates a nonlubricated neovagina due to lack of columnar epithelial cells that is prone to stenosis and requires regular dilatation and intensive longitudinal postsurgical care (7, 23). It is therefore possible that this creates a more inflammatory milieu both due to mechanical abrasion and potentially substandard long-term care. In addition, neovaginas reconstructed by penile skin inversion have diverse polymicrobial communities that can increase immune activation and decrease epithelial barrier function (24).
“Here, we report evidence that the unique biology of TGW sets them apart from CW and men who have sex with men (MSM). This includes (i) a higher inflammatory environment in the neovagina reconstructed by penile skin inversion that may be driven by a highly diverse microbiome, (ii) an increase in CCR5 expression in the intestinal mucosa related to hormonal levels, and (iii) distinct rectal microbiome composition impacting gut mucosal homeostasis.”
(Joke warning: when I tried to type “feminizing” my iPhone decided I meant “demonizing.” Now, that is the problem with World!!!)
But back to “elevated inflammation.”
From August 2023,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543719/
Distinct mucosal and systemic immunological characteristics in transgender women potentially relating to HIV acquisition
Good read. Seems this through line might be what Dr J is thinking of for our small trial in HIV patients in hormonal treatments with elevated inflammation, at least at the site of the neo-vagina, still looking for blood ID's.
Here’s a couple of quotes to pass the time.
“Transgender women (TGW) are disproportionally affected by HIV infection, with a global estimated prevalence of 19.9%, often attributed to behavioral risk factors, with less known about biological factors. We evaluated potential biological risk factors for HIV acquisition in TGW at the sites of viral entry by assessing immune parameters of the neovaginal surface and gut mucosa. The neovagina in TGW, compared with the vagina in cisgender women (CW), shows distinct cell composition and may pose a more inflammatory environment, evidenced by increased CD4+ T cell activation and higher levels of soluble markers of inflammation (C-reactive protein, soluble CD30). Increased inflammation may be driven by microbiome composition, as shown by a greater abundance of Prevotella and a higher Shannon Diversity Index. In addition, we have observed higher frequency of CD4+CCR5+ target cells and decreased DNA methylation of the CCR5 gene in the gut mucosa of TGW compared with CW and men who have sex with men, which was inversely correlated with testosterone levels. The rectal microbiome composition in TGW appears to favor a proinflammatory milieu as well as mucosal barrier disruption. Thus, it is possible that increased inflammation and higher frequencies of CCR5-expressing target cells at sites of mucosal viral entry may contribute to increased risk of HIV acquisition in TGW, with further validation in larger studies warranted.”
And furthermore,
“TGW undergo feminizing hormone treatment to increase female characteristics, which includes the usage of progestogens, estrogens, and antiandrogens (5). Recommended feminizing hormone regimens are composed of estrogen to promote female secondary sexual characteristics and androgen-lowering drugs to inhibit male secondary sexual characteristics by decreasing endogenous testosterone production or testosterone activity (6, 7). However, in Thailand, there is high use of feminizing hormone treatment reported outside the reference regimen as these drugs can be purchased without a medical prescription (
. Progesterone and estrogen are known to have differential effects on mucosal epithelial barriers, modulating cellular expression of CCR5, the primary co-receptor for entry of R5 tropic HIV into CD4+ T cells (9), and α4β7, a cellular gut-homing marker (10), as well as on vaginal epithelial thickness (11, 12). Sex hormone levels are also linked to inflammation, induced by the impact they have on the composition of microbial communities…” Sorry in advance guys…please read on…
“Gender affirmation surgery (GAS) by vaginoplasty aims to create a functional vagina which can be achieved by a variety of surgical techniques including penile skin inversion, colonic flap, or peritoneal flap vaginoplasty (21, 22). Currently, penile skin inversion is the most widely used technique for GAS. The cell composition of the skin creates a nonlubricated neovagina due to lack of columnar epithelial cells that is prone to stenosis and requires regular dilatation and intensive longitudinal postsurgical care (7, 23). It is therefore possible that this creates a more inflammatory milieu both due to mechanical abrasion and potentially substandard long-term care. In addition, neovaginas reconstructed by penile skin inversion have diverse polymicrobial communities that can increase immune activation and decrease epithelial barrier function (24).
“Here, we report evidence that the unique biology of TGW sets them apart from CW and men who have sex with men (MSM). This includes (i) a higher inflammatory environment in the neovagina reconstructed by penile skin inversion that may be driven by a highly diverse microbiome, (ii) an increase in CCR5 expression in the intestinal mucosa related to hormonal levels, and (iii) distinct rectal microbiome composition impacting gut mucosal homeostasis.”
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