Gender-affirming hormones and antiretroviral therapy: implications on adherence and clinical outcomes Asa Radix, MD, MPH, FACP Director of Research and Education, Callen-Lorde Community Health Center Clinical Associate Professor of Medicine, NYU

Conflict of Interest No conflicts of interest to declare

Outline What are gender affirming medical interventions? What impact does provision of hormones have on HIV prevention, treatment and care? What additional considerations exist for the use of hormone therapy and ART?

Gender-Affirming Medical Treatments Hormone therapy, androgen blockers Surgeries Speech therapy Hair removal Image source: Callen-Lorde Community Health Center, New York, New York

Medical Transition Feminizing Masculinizing Hormones (estrogen) Androgen blockers Breast augmentation Vaginoplasty & labiaplasty Orchiectomy Tracheal shave Facial bone reduction Rhinoplasty Hormones (testosterone) Chest masculinization hysterectomy, salpingo- oophorectomy Phalloplasty Metoidioplasty Vaginectomy Scrotoplasty Urethroplasty Testicular prostheses

Early Medical Treatment* Methyltestosterone 1935 Diethylstilbestrol 1938 Conjugated estrogens1941 Ethinyl estradiol 1943 *No longer used for medical transition

Feminizing Regimens Anti-androgen * Starting Dose Average Dose Maximum Dose Spironolactone, oral 25mgday 150mg/day 400mg/day Finasteride, oral 1mg/day 1-5mg/day 5mg/day Cyproterone, oral 50mg/day 100mg/day Goreselin, sc 3.6 mg/month or 11.25 mg/3 months   Leuprolide acetate, im 3.75 mg/month Estrogen Estradiol valerate oral 2mg/day 4mg/day 8mg/day Estradiol valerate 20mg IM q 2 wks 20-40 IM q 2 wks 40 mg IM q 2 wks Estradiol patch (preferred over 45) 25 mcg/day 50 mcg/day 200mcg/day Adapted from Hembree, JCEM 2009, 94(9):3132–3154 Royal College of Psychiatrists, 2015

Feminizing Regimens Breast development Redistribution of body fat Reduced muscle mass & stamina Reduced body hair (not facial) Reduced erectile function Reduced size of testes Lower sperm count Image source: Callen-Lorde Community Health Center, New York, New York Hembree, JCEM 2009, 94(9):3132–3154

Masculinizing Regimens Hormone Starting Dose Average Dose Maximum Dose Testosterone (cypionate or enanthate) im Depo-Testosterone® 50 mg q 2w 200 mg q 2 w 200 mg q 2 Transdermal Testosterone 1% 25 mg daily 50 mg daily 100 mg daily Testosterone patch 1-2.5g daily 4-5g daily 7.5-8 g daily Testosterone undecanoate im 750 mg/10 weeks Measure testosterone levels between injections Goal: 320-1000 ng/dL Adapted from Hembree, JCEM 2009, 94(9):3132–3154

Masculinizing Regimens Facial and body hair Redistribution of body fat Increased muscle mass Deepened voice Male-pattern baldness Cessation of menses Clitoromegaly Atrophic vaginitis Hembree, JCEM 2009, 94(9):3132–3154

Hormones also… Improve quality of Life Reduce perceived stress, anxiety, depression Improve social functioning Improve sexual function Reduce in cortisol levels Gorin-Lazard A, et al. J Sex Med. 2012 Newfield E,et al. Quality of Life Research. 2006 Gómez-Gil E, et al. Psychoneuroendocrinology. 2011 Meier SLC, et al. Journal of Gay & Lesbian Mental Health. Costantino A, et al J Sex Marital Ther. 2013 Colizzi M, et al. J Sex Med. 2013 Dec

Antiretrovirals & Hormone Therapy

Transgender Women and ART HIV+ Less likely to receive ART More likely to report lower adherence More likely to have detectible viral load Higher HIV-related mortality HIV- Lower rates of PrEP uptake Lower adherence to PrEP Melendez et al, APJH 2005 Sevelius et al, JANAC, 2010 San Francisco DPH HIV/AIDS, 2008 Deutsch MB, et al. Lancet HIV. 2015 Wilson E, et al. 2015. PLoS One. Sevelius JM, et al. Glob Public Health. 2016

Ryan White HIV/AIDS Program Services Report, 2015 Retention in Care Viral Suppression Total population N= 531,816 Total Transgender Population, N=6020 (1.1%) Percent Percent Ryan White HIV/AIDS Program Annual Client-Level Data Report Ryan White HIV/AIDS Program Services Report (RSR) https://hab.hrsa.gov/sites/default/files/hab/data/datareports/2015rwhapdatareport.pdf

Why less likely to adhere? Prioritization of transition-related medical care over HIV care Fears about drug interactions between hormones and HIV Lower adherence self-efficacy Negative experiences with providers/health systems Fear of stigma & discrimination Sevelius J, et al. J Assoc Nurses AIDS Care. 2010 ; 21(3): 256–264 Sevelius J, et al. AIDS Care. 2014 August ; 26(8): 976–982 Chung, et al. 2016. Transgender Law Center

Why less likely to adhere? Prioritization of transition-related medical care over HIV care Fears about drug interactions between hormones and HIV Lower adherence self-efficacy Negative experiences with providers/health systems Fear of stigma & discrimination Sevelius J, et al. J Assoc Nurses AIDS Care. 2010 ; 21(3): 256–264 Sevelius J, et al. AIDS Care. 2014 August ; 26(8): 976–982 Chung, et al. 2016. Transgender Law Center

Antiretrovirals & Hormones Data based on studies with oral contraceptives (ethinylestradiol) Estrogens metabolized by cyp3A4 Protease inhibitors & NNRTI interactions possible - Avoid using unboosted fosamprenavir with estrogens – APV Cmin decrease 20% DHHS. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. 2016 Radix A et al. JIAS 2016, 19(Suppl 2):20810

Check estradiol levels may need to decrease dose Radix A et al. JIAS 2016, 19(Suppl 2):20810

Check estradiol levels may need to increase dose Radix A et al. JIAS 2016, 19(Suppl 2):20810

Hormone access improves engagement Hormones are a primary motivator for seeking medical care, improves retention Adherence to hormone therapy predicts high ART adherence When HIV providers are hormone prescribers, improves ART adherence Sevelius, J. Ann Behav Med. 2014 February ; 47(1): 5–16 Sevelius J, et al. J Assoc Nurses AIDS Care. 2010 ; 21(3): 256–264 Sevelius J, et al. AIDS Care. 2014 August ; 26(8): 976–982 Deutsch M, et al. 2015 NHPC.

Gender Identity Engagement Integrating hormones into HIV care Gender-affirming care environment Knowledge about ART/HT Competent providers/systems Trans staff Gender Identity Engagement Stigma and discrimination Provider mistrust Lack of provider awareness Fear about drug interactions Social marginalisation

Steps to Improve HIV Prevention & Care Co-locate/integrate HIV services & hormone care Train providers to deliver hormone therapy Antiretrovirals – discuss safety with hormones Trans inclusive materials Hire trans staff https://www1.nyc.gov/assets/doh/downloads/pdf/ah/transgender-womens-health-booklet.pdf

Acknowledgements Callen-Lorde Trans Ops Team Peter Meacher, MD Pedro Carneiro, MPH William Nazareth aradix@callen-lorde.org @aeradix @callenlorde