Plasma and intracellular pharmacokinetics of tenofovir disoproxil fumarate and emtricitabine in transgender women receiving feminizing hormone therapy.

BACKGROUND: Transwomen have an increased risk of HIV acquisition compared with other adults. Drug-drug interactions between pre-exposure prophylaxis (PrEP) and gender-affirming therapy are cited as a reason for poor PrEP uptake among transwomen. We evaluated plasma tenofovir and emtricitabine pharmacokinetics and their active intracellular anabolites, tenofovir-diphosphate and emtricitabine-triphosphate, in transwomen receiving feminizing hormones. METHODS: We enrolled HIV-negative transwomen (≥19 years) not receiving PrEP. Participants took oral tenofovir disoproxil fumarate/emtricitabine 300/200 mg daily for 14 days. Plasma was collected at 0 h (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 12 h on day 14 post-tenofovir disoproxil fumarate/emtricitabine dose. The plasma AUC0-24 was calculated using the trapezoidal rule and compared with historical HIV-negative cisgender adults as geometric mean ratios (GMRs, 90% CI). Secondarily, tenofovir-diphosphate and emtricitabine-triphosphate from PBMCs collected at 0 h and 12 h were reported descriptively as geometric means (90% CI). Clinical trials registration: NCT03270969. RESULTS: Among 15 transwomen (mean age 32 years), geometric mean tenofovir and emtricitabine plasma AUC0-24 were lower compared with controls: tenofovir, 2.10 versus 2.76 mg·h/L, GMR 0.76 (0.65-0.90), P = 0.01; emtricitabine, 9.15 versus 10.64 mg·h/L, GMR 0.86 (0.75-0.98), P = 0.07. Tenofovir-diphosphate and emtricitabine-triphosphate concentrations were higher than previously reported in the literature: 167.1 (146.6-190.5) fmol/106 cells and 15.4 (13.8-17.3) pmol/106 cells, respectively. CONCLUSIONS: We observed lower plasma tenofovir and emtricitabine concentrations in transwomen compared with historical cisgender adults, yet intracellular tenofovir-diphosphate and emtricitabine-triphosphate concentrations were higher than previously reported in PBMCs. Understanding the differences of PrEP pharmacokinetics in plasma and tissue compartments and the resultant impact on efficacy remains important for transwomen.

Care of the Transgender Patient with a Pulmonary Complaint.

Individuals who identify with a gender not typically associated with their sex assigned at birth are a growing population worldwide. Guidelines to help healthcare providers navigate the care of gender minorities (GMs) are often aimed at primary care providers and may be too general for subspecialists. Pulmonologists may see GM individuals for a variety of reasons, and no reference exists that contains relevant information about GM-specific care, including unique conditions to consider. A systematic review was completed to identify unique characteristics in caring for GM patients with a pulmonary complaint.

Integrated Comprehensive Care for Transcare and Gender Diverse Clinic Patients: An Assessment of Physical, Mental, and Social Needs.

Introduction There is a large body of research reporting the healthcare needs of groups identifying as lesbian, gay, bisexual, transgender, and/or queer (LGBTQ); however, a gap exists in the research literature because many epidemiological studies focus on sexual orientation rather than gender identify/incongruence. To address the lack of specific data from transgender and gender diverse (TGD) individuals, our organization designed and deployed a survey to assess the gender-affirming physical, mental, and social care needs of current patients. Methods A group of subspecialty physicians currently working with TGD patients created a list of questions and requested feedback from medical professionals familiar with the healthcare needs of this population. In addition, patients reviewed the survey for content and clarity. The final 68-item survey was distributed in April 2020 to patients or patients' representatives with an email address on file at the Nebraska Medicine Transgender Care Clinic (NMTCC). Participants were asked to respond to questions regarding their gender identity, their transition-related medical decisions, and their interest in services. Results Invitations were sent to 690 patients and 168 surveys were completed (response rate: 24.3%). Over 90% (n = 153) of the participants were patients and 9% (n = 15) answered survey questions on the patient's behalf. A majority (77.2%) had started the medical transition (hormones or puberty blockers) in the past four years. Nearly half (46.4%) identified as trans women, 43.4% identified as trans men, and 10.2% indicated they were nonbinary or gender expansive. Participants' sex assigned at birth was 50.9% female and 46.1% male. Most patients (n = 149; 92%) reported currently receiving hormone treatment within the Nebraska Medicine healthcare system. Results indicated the highest level of clinical services interest was primary care (38.4%), gender-affirming surgery (73.5%), voice therapy (49.0%), and hair removal (37.5%). In addition, participants were very likely to participate in support groups with "people of similar gender identity" (32.9%), with "others around my age" (28.6%), and "including a mix of ages and identities" (26.9%). Discussion This study suggests that our TGD patients would utilize integrated services to access a variety of clinical and non-clinical services. Ongoing community engagement and direct feedback from patients are critical to the success and growth of our gender-affirming care clinic. The results of this study will inform the planning and further evolution of a program designed to build trust and address health inequities for TGD individuals throughout the region.

iPLEDGE allegiance to the pill: evaluation of year 1 of a birth defect prevention and monitoring system.

The United States Food and Drug Administration (FDA), in collaboration with pharmaceutical manufacturers, have recently implemented a heavily revised risk-management program for patients on isotretinoin (Accutane), a drug with known and pronounced teratogenic effects. This revised risk management plan places significant burdens on both providers and patients in the hopes of achieving its goal of reducing fetal exposure to isotretinoin. The main focus of this paper is to discuss the burdens of various aspects of the program in relationship to potential corresponding benefits. In particular, we evaluate the pregnancy rates of women on isotretinoin therapy compared with that of the general population and the rate changes based on the risk management programs. Additionally, we investigate whether the benefits of the program for women have increased as the benefits have risen. We devote special attention to the ethical implications of the intent of the program and to an analysis of the ethical justification of the restrictions placed on women of childbearing potential (WCP) as it compares to the risk-benefit relationship of using isotretinoin.

Women and contraception in research: a pilot study.

BACKGROUND: There are no data on women's willingness to participate in clinical trials as a function of real or perceived reproductive risk. Further, it is unknown whether the requirement for contraception or the common practice of limiting women's contraceptive choices influences their willingness to participate in research. The uncertainty about women's preferences on these matters remains a barrier for recruiting women to and retaining women as subjects in clinical trials. METHODS: We developed a pilot study to determine women's willingness to participate in research with contraceptive requirements by looking at the three most common types of reversible contraceptives: hormonal contraception, barrier contraception, and intrauterine contraception. This study tested the hypotheses that restrictions on contraceptive choice impact women's willingness to participate in research and that the impact of contraceptive choice differs depending on women's perception of risk. RESULTS: Women's willingness to participate in the proposed study decreased overall as reproductive risk increased. In addition, requirements for specific contraceptive methods negatively impacted women's reported willingness to participate in the research studies in our survey. CONCLUSIONS: Results suggest that requirements for specific contraceptive methods negatively impacted women's reported willingness to participate in research. If confirmed in a larger sample, the negative effect of contraceptive limitations on women's willingness to participate in research would be of importance to clinical investigators and to institutional review boards (IRBs), as most adult biomedical research has as an explicit goal the equitable recruitment of women of childbearing potential.