Gender-affirming hormone therapy would also not affect the effectiveness of this biomedical HIV prevention tool when taken together.

The joint administration of gender-affirming hormone therapy (THAG) and pre-exposure prophylaxis against HIV (PrEP) in Brazilian trans women does not cause clinically significant alterations in drug concentrations that could affect their efficacy. The administration of PrEP against HIV - tenofovir disoproxil fumarate (TDF) / emtricitabine - in trans women taking THAG - estradiol and spironolactone - did not alter hormone levels in a clinically relevant way. Neither were clinically significant alterations determined when the effect of THAG on PrEP drug levels and that could affect its efficacy was analyzed. These are the main findings of two Brazilian studies whose results have been presented at the XI Conference of the International AIDS Society on HIV Science (IAS 2021), held last week virtually due to the COVID-19 pandemic.

 

Many studies have analyzed the effectiveness of pre-exposure prophylaxis against HIV (PrEP) in trans people who are taking hormonal treatment - either in the form of testosterone in trans men or in the form of estrogens in trans women -, some of them pointing to the possible existence of interactions between the medications included in PrEP and hormonal treatments. Two US studies have analyzed the interaction of gender affirming hormone therapy (THAG) and HIV pre-exposure prophylaxis (PrEP) in young trans men and women.

With the aim of offering more evidence on this question, a team of researchers from the Oswaldo Cruz Health Institute (FIOCRUZ) in Rio de Janeiro conducted two paired studies with trans women. The first study included 33 trans women who were at risk of acquiring HIV and focused on the effect of PrEP versus HIV on gender-affirming hormone therapy. Participants began receiving a standardized THAG based on the feminizing hormone estradiol and the testosterone blocker spironolactone.

After taking the THAG for two weeks, the blood hormone levels were measured, not just once, but multiple times over the course of a day (with the first determination made immediately before the participants received the THAG) to have a idea of ​​total drug exposure. The participants then began taking PrEP for HIV as well. After 12 weeks of taking THAG and PrEP, THAG blood levels were retested to see if they had changed.

The mean age of the 33 participants was 26 years old and their ethnic origin –according to the Brazilian classification– was 25% black, 21% white, 50% mixed (“brown”) and 4 % other (such as Asian or Native American). Their body mass index (BMI) was within the normal range, with none of them being obese or underweight, an important consideration in drug level studies. No participant had evidence of liver or kidney dysfunction that would have excluded them.

The initial THAG regimen consisted of estradiol valerate 2mg or 4mg daily and spironolactone 100mg or 200mg daily, both administered orally. Some variation in dosage was allowed; thus, initially, four of the 33 women took the highest dose of estradiol and three, the highest dose of spironolactone.

At week 12, a total of 24 women were able to contribute data to the full study. The mean doses of the two hormone treatment medications - that is, estradiol and spironolactone - increased slightly over the 12 weeks. At that time, six women of the remaining 24 were taking 4mg of estradiol and one 6mg, while ten were now taking 200mg of spironolactone and one had stopped taking it entirely due to side effects (she was excluded).

 

Mean blood levels of both THAG drugs decreased slightly between study start and week 12. The maximum concentration (Cmax) or peak level of estradiol decreased from 36 to 28.3 picograms per milliliter (pg / mL) and total drug exposure over 24 hours (the area under the concentration curve or AUC) decreased from 596 to 511 pg / mL. None of these decreases were statistically significant.

Spironolactone Cmax decreased only marginally and not significantly from 0.9 to 0.8 nanograms per milliliter (ng / mL). The reduction in AUC –from 3.0 to 2.8 ng / mL–, although it was also relatively slight, did have statistical significance (p = 0.008), although it is probably not clinically significant. There was a case of one participant who had a very high estradiol AUC, about 13 times the mean, at the start of the study, but which had decreased to about five times the mean by week 12.

The second study included 38 trans women who were divided into two groups. One group included 14 participants who took HIV PrEP alone for 12 weeks without receiving THAG. The other group consisted of 24 participants who took PrEP together with THAG. The gender affirming therapy used was the same as in the first study, ie estradiol and spironolactone.

At week 12, the participants came one day to offer multiple blood samples for the determination of drug levels, as in the previous study, although this time the doses of PrEP and THAG taken that day were directly observed, to avoid administration before the first blood sample. The women also offered dried blood samples, to provide evidence of the mean level of adherence to PrEP over the previous 12 weeks.

After week 12, a smaller group of 17 women continued in the study, and all were allowed to take an individualized regimen of THAG in addition to PrEP. After 30 to 48 weeks taking THAG and PrEP, blood samples were taken to determine drug levels and also provided dried blood samples for adherence monitoring.

At week 12, it was found that the peak levels of the two PrEP drugs, one hour after taking, were higher in the group that also took THAG than in the group that took only PrEP. The approximate peak levels of tenofovir disoproxil fumarate were 330 ng / mL in the PrEP and THAG group and 225 ng / mL in the PrEP-only group. Emtricitabine levels were 1,800 ng / mL in the PrEP and THAG group, and 1,450 ng / mL in the PrEP alone group. These differences were statistically significant (p ≤0.001 and p ≤0.03 for tenofovir and emtricitabine, respectively).

However, the area under the concentration curve (AUC) or total drug level was similar between the two groups, and the trough (lower) levels 24 hours after taking the doses were identical. The efficacy of PrEP would not be affected by these differences, and no drug-related adverse events were observed that could be linked to the slightly higher levels of THAG. Weight (BMI) was moderately associated with tenofovir levels and slightly emtricitabine levels, and higher BMI was associated with somewhat lower PrEP levels.

Dry blood samples at week 12 revealed that adherence to PrEP was quite high, as 73% of all participants had intracellular drug levels suggesting that they had received at least four doses of PrEP per week, at as did 79% in the group that also took THAG and 64% in the group that only took PrEP.

At the second time of taking blood samples to determine drug level, between weeks 30 and 48, only 15 participants provided samples that could be evaluated, showing peak levels of PrEP drugs halfway between the levels observed in the two groups at week 12 (about 280 ng / mL of tenofovir disoproxil fumarate and 1,680 ng / mL of emtricitabine). These levels were no longer statistically different from those seen at week 12 in the PrEP-only group. Again, the AUC and trough levels were basically identical to those at week 12. On the other hand, adherence had improved, with 14 of 15 participants (93%) having levels associated with at least four doses per week, although this is what was expected in the self-selected and presumably highly motivated group that remained in the study.

In conclusion, the team of researchers noted that their findings provide evidence that there is no clinically relevant impact of feminizing hormone therapy on systemic PrEP concentrations and, therefore, on its efficacy in trans women at high risk of acquire HIV.

Source: Aidsmap /Elaboración propia (gTt).

References: Berg Cattani V et al. No impact of tenofovir/emtricitabine in estradiol exposure among transwomen on oral PrEP: results from the 12-week drug-drug interaction PrEParadas substudy. 11th IAS Conference on IAS Science, abstract no OALC0601, 2021.

Berg Cattani V et al. No impact of feminizing hormone therapy on daily oral pre-exposure prophylaxis effectiveness among Brazilian trans women vulnerable to HIV infection: the PrEParadas Study. 11th IAS Conference on IAS Science, poster abstract no 2021.

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