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

Title
No impact of feminizing hormone therapy on daily oral pre-exposure prophylaxis effectiveness among Brazilian trans women vulnerable to HIV infection ' the PrEParadas Study
Presenter
Vitoria Berg Cattani
Authors
V.B. Cattani * (1), E. Jalil (1), T. Torres (1), S. Cardoso (1), L. Eksterman (1), C. Castro (1), L. Monteiro (1), P. Anderson (2), B. Lane (2), E. Wilson (3), V. Veloso (1), B. Grinsztejn (1), R. Estrela (1)
Institutions
(1) Evandro Chagas National Institute of Infectious Diseases INI Fiocruz, Rio de Janeiro, Brazil, (2) University of Colorado, Denver, United States, (3) University of California, San Francisco, United States

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.