Drug-drug Interactions Among Thai Transgender Women Living with Human Immunodeficiency Undergoing Feminizing Hormone Therapy and Antiretroviral Therapy: The iFACT Study. (25th February 2020)

• Record Type: Journal Article
• Authors: Hiransuthikul, Akarin; Himmad, Linrada; Kerr, Stephen J; Janamnuaysook, Rena; Dalodom, Theera; Phanjaroen, Kannapat; Pankam, Tippawan; Kongkapan, Jiratchaya; Mills, Stephen; Vannakit, Ravipa; Phanuphak, Praphan; Phanuphak, Nittaya
• Is Part Of: Clinical infectious diseases. Volume 72:Number 3(2021)
• Page Start: 396
• Page End: 402
• Publication Date: 2020-02-25
• Subjects: antiretroviral therapy -- drug-drug interactions -- feminizing hormone -- transgender women; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciaa038
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: Drug-drug interactions between feminizing hormone therapy (FHT) and antiretroviral therapy (ART) are a major concern among transgender women (TGW), which may lead to suboptimal ART adherence and inappropriate FHT dosage. To evaluate potential drug-drug interactions between FHT and ART, we performed intensive measurements of the pharmacokinetic (PK) parameters of blood tenofovir (TFV), efavirenz (EFV), and estradiol (E2). Methods: Twenty TGW with newly diagnosed human immunodeficiency virus (HIV) infection were enrolled. FHT (E2 valerate 2 mg/d and cyproterone acetate 25 mg/d) was prescribed at baseline until week 5 and restarted at week 8. ART (TFV disoproxil fumarate/emtricitabine/EFV at 300/200/600 mg) was initiated at week 3. The E2 PK parameters were measured intensively at weeks 3 (without ART) and 5 (with ART), and TFV and EFV PK parameters were measured intensively at weeks 5 (with FHT) and 8 (without FHT). Results: The median (interquartile range) age and body mass index were 25.5 (22.5–31.0) years and 20.6 (19.3–23.1) kg/m 2, respectively. The differences in geometric mean ratios between weeks 3 and 5 were as follows for E2 area under the curve, maximum concentration, and concentration at 24 hours ( C 24 ), respectively: 0.72 (90% confidence interval, .64–.81; P < .001), 0.81 (.72–.92; P = .006), and 0.64 (.50–.83; P = .004). The differences in geometric mean ratios between weeks 5 and 8 were as follows for TFV AUC, TFV C 24, and EFV C 24 : 0.86 (90% confidence interval, .80–.93; P = .002), 0.83 (.75–.93; P = .006), and 0.91 (.85–.97; P = .02). Conclusions: Among HIV-positive TGW, E2 PK parameters were significantly lower in the presence of TFV disoproxil fumarate/emtricitabine/EFV, and some TFV and EFV PK parameters were lower in the presence of FHT. Further studies should determine whether these reductions are clinically significant and whether they occur with other FHT or ART regimens. Abstract : There is a significant reduction in blood E2 concentration (36%) in the presence of efavirenz (EFV)-based antiretroviral therapy; and blood tenofovir (TFV) and EFV concentrations are significantly reduced by 17% and 9%, respectively, in the presence of feminizing hormone therapy.