No impact of feminizing hormone therapy on daily oral pre-exposure prophylaxis effectiveness among Brazilian trans women vulnerable to HIV infection ' the PrEParadas Study


BACKGROUND: Interactions between feminizing hormone therapy (FHT) and oral pre-exposure prophylaxis (PrEP) components (tenofovir disoproxil fumarate and emtricitabine [FTC]) could negatively affect PrEP outcomes among trans women. We aimed to evaluate the impact of FHT on PrEP pharmacokinetics (PK) in a nested study of a trans-specific PrEP demonstration conducted in Rio de Janeiro, Brazil.
METHODS: According to their will to use FHT, a subgroup of PrEParadas (NCT03220152) participants were assigned to receive PrEP only (Group 1) or standardized FHT (estradiol valerate+spironolactone) plus PrEP (Group 2) for 12 weeks, after a washout period. The first PK evaluation (PK1) was at week 12. Afterwards participants from both groups could start any FHT (real-life FHT); those on PrEP and real-life FHT were evaluated on a second longer-term PK evaluation (PK2) between weeks 30-48. Blood samples were collected pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours after directly observed dosing. We estimated PK parameters by non-compartmental analysis and evaluated correlations between covariates and tenofovir (TFV) or FTC area under the curve from zero to 24 hours (AUC0-24) by Spearman rank correlation (alpha=0.05). PrEP adherence was estimated using dried-blood spots (DBS) levels.
RESULTS: We analyzed data from 38 PK1 participants (Group 1: 14, Group 2: 24) and 17 in PK2. TFV and FTC Cmax on PK1 were significantly lower in Group 1 (254[222-290] and 1627[1434-1952] ng/mL) compared to Group 2 (318[278-396] and 1948[1662-2294] ng/mL). TFV and FTC parameters did not differ between PK1 (Group 1) and PK2 (both groups on PrEP+real-life FHT). Body mass index was significantly associated with lower TFV or FTC AUC0-24 (rho -0.55, p=<0.001, and rho -0.30 p=0.03, respectively). DBS levels on PK1 were compatible with 4+, 2-3, <2 FTC/TDF doses per week among 28 (73.0%), 4 (11.0%), and 6 (16.0%) participants, respectively. Almost all participants with DBS available on PK2 had levels compatible with 4+ FTC/TDF doses (14/15, 93.3%). There were no seroconversions during the study follow-up.
CONCLUSIONS: Our results provide further evidence that there is no clinically relevant impact of FHT on PrEP systemic concentrations and thereby effectiveness among trans women at high risk of HIV.