HRT for trans women could affect the efficacy of HIV pre-exposure prophylaxis (PrEP)

Disclaimer: I am not a medical professional and this is not medical advice.

I’ve previously written about a published case series in which HIV-positive trans women taking the antiretroviral medication efavirenz were found to have abnormally low estrogen levels when taking oral estradiol, suggesting that this medication may interfere with the efficacy of oral estrogen. While this was addressed in these cases by switching to other HIV medications or other routes of delivery of estrogen, a recent study suggests that trans women on HRT may face a more troubling drug interaction: taking estrogen may interfere with and lower blood levels of the HIV pre-exposure prophylaxis medication Truvada (tenofovir disoproxil fumarate/emtricitabine), potentially rendering it less effective at preventing infection.

Shieh et al. (2019) examined eight trans women with estradiol concentrations of at least 100 pg/mL who took daily PrEP for one week, and compared their blood levels of the medications used in Truvada to a control group of cisgender men. Among the trans women in this study, blood levels of these medications were 24% to 32% lower than those of cis men:

Plasma TFV and FTC C24 (trough) concentrations in TGW were lower by 32% (p = 0.010) and 32% (p = 0.038) respectively, when compared to CGM. Plasma TFV and FTC 24‐hr area under the concentration‐time curve in TGW trended toward and was significantly lower by 27% (p = 0.065) and 24% (p = 0.028) respectively.

Negative correlations were found between estrogen dose and blood concentration of PrEP. The authors note that the specific mechanism by which HRT may reduce blood levels of PrEP is “not clear”; however, the association between HRT in trans women and significantly lower blood levels of PrEP has also been found in other studies, including Hiransuthikul et al. (2019) and Cottrell et al. (2019).

So how does this impact the efficacy of PrEP at preventing HIV infection? The authors state that the blood levels observed in this study are comparable to taking PrEP only five or six days a week rather than daily:

The magnitude of reduced plasma TFV and FTC exposure associated with GAHT regimens in these studies is consistent with taking only five doses (Hopkins) or six doses (iFACT) per week when compared to taking 7 daily TDF/FTC doses each week, based on HPTN 066 directly observed TDF/FTC dosing.

The authors suggest that while daily PrEP may still provide protection, as a previous study found it to be effective with only four doses a week, the “on-demand” or 2-1-1 dosing regimen of PrEP (2 doses taken 2-24 hours before condomless anal sex, followed by one dose 24 hours later and one dose 24 hours after that) may not offer sufficient protection for trans women on HRT:

Theoretically, one would expect the combination of reduced concentrations from both the 2‐1‐1 regimen and GAHT to result in a dose frequency equivalent of two to three doses per week. At this dose frequency, PrEP efficacy in the iPrEx models would predict reductions in PrEP efficacy. Accordingly, it seems prudent to recommend against the 2‐1‐1 regimen in TGW on GAHT, at least until more rigorous PK studies address optimal PrEP dosing in TGW.

Trans women face a highly elevated prevalence of HIV, with 14% of trans women in the United States estimated to be HIV-positive, including 26% of Hispanic/Latina trans women and 44% of black trans women (Becasen et al., 2019). PrEP offers a critical opportunity to prevent the spread of HIV in this vulnerable population, and trans women who choose to take PrEP should be aware of how to use it most effectively. ■