Antiretroviral Therapy in Transgender women

1. AntiretroviralTherapy in Transgender women Dr. Omar Sued Fundación Huésped

2. Whatdoestransgender mean? • “Transgender woman” or “transwoman” (TGW) is applied to people that were assigned male sex at birth and now express their gender identity as female. • Transvestite, transsexual, transgender.

3. What is the prevalence? Depends on the definition used In registries: 0.6 per 100,000 BUT by self reporting: 0.5% Collins et al J Sex Med 2016

4. Trans HealthResearch: Frompathologytoresilience Sweileh BMC International Health and Human Rights (2018) 18:16

5. Are transgender women more vulnerable than cisgender women?

6. Noemi’sstory • Born in a small town in the countryside, she was assigned the male sex at birth. At age 10 she started to talk of herself as a woman. • Her parents consulted with pediatricians, endocrinologists and even with traditional healers hoping to “cure their son”. • At the secondary school, after being sanctioned several times for not respecting the “uniform etiquette for boys” she quit. • She changed clothes in secret and escaped at night, from home, to meet new people. She started using oral contraceptives hoping to improve her feminine appearance. • At age 17, after an argument with her parents, she ran away. She moved to Buenos Aires, where, without money or housing, she engaged in sex-work as a way to subsist.

7. Risks and vulnerabilities Fundación Huesped, ATTTA survey, n500

8. 41% of TGW avoid seeking healthcare  • Discrimination by healthcare workers (aOR = 3.36) • Discrimination by other patients (aOR = 2.57) • Currently living in Buenos Aires area (aOR = 2.32) • Been exposed to police violence (aOR = 2.20) • Internalized stigma (aOR = 1.60) No access to healthcare = unsupervised self-prescription “Live and die in a country of Machos”

9. Risk of self-prescribed Gender Affirming (GA) treatments Silicone-relatedproblems: • Pulmonaryembolism • Local infections • Disfigurement • Autoimmunity • Potential transmission of bloodborne pathogens Problemsassociatedwithunsupervised, self-prescribed hormonal therapy : • Pituitary gland tumor • Breast cancer • Pulmonary embolism • Deep vein thrombosis • Hepatotoxicity-Dyslipidemia Gender Affirming (GA) procedures are those procedures such as hormonal treatment, surgeries, speech therapy and hair removal used by transgender individuals to affirm their own gender identity

10. Higher exposure and no healthcare access: Explosive combo The life expectancy of transgender women in Argentina has been estimated to be 35 years Argentina data: Dos Ramos Farias et al, JID 2011, Frola C et al: IAS 2017, Angionio A SADI 2014 But similar to international literature: Baral S Lancet 2012, NSAIDs: Non-steroidal Anti-inflammatory Drugs

11. HIV prevention and care for TGW

12. 10 tipsforimproving HIV carefor TGW in yourclinic • Work with the communities’ leaders and champions • Include transgender personnel on your staff • Always ask for, and use “chosen” and not “legal” names • Create a welcome and inclusive environment • Develop policies for addressing discrimination in your site • Be sensitive and non-judgmental • Do not assume all TG are at high risk for HIV, or are HIV-positive • Don´t be invasive, askonlyrelevantquestions • Do not ask about their genital status if it is not medically needed • Ask permission before disclosing their gender to others Adapted from Kosenko K, Rintamaki L, Raney S, Maness K. Transgender patient perceptions of stigma in health care contexts. Med Care. 2013 Sep;51(9):819–22. Melendez RM, Pinto RM. HIV prevention and primary care for transgender women in a community-based clinic. J Assoc Nurses AIDS Care. 2009;20:387–97.

13. Expanded Access totesting and careiskey • Use rapid HIV tests • Offer self-testing • Support community testing • Promote domiciliary testing • Offer domiciliary care for certain individuals • Link withPrEP or ART according to results • Consider integrated testing / same-day result tests (Syphilis, HBsAg, HCV, Xpert for TB, NG-CT) • Provide vaccinations, and condoms TUAC01 Zalazar V et al. Acceptability of HIV and syphilis domiciliary testing among transgender women in Buenos Aires, Argentina

14. Antiretroviraltherapy • Ideally, start same-day treatment • Consider community HIV resistance and drug availability • Choose drugs with low potential for interactions and high forgiveness • Prefer drugs without metabolic impact • Provideextensiveeducationabout HIV drugs, harmreduction & DDIs • Recognize the “non-virological” benefits: • ↓ Alcohol and Drug Abuse • Anxiety • ↓ Stigma • ↑ Quality of life

15. RetentionistheAchilles´ heel of ART among TGW TransVIIVStudy 61 Naive TGW initiating DTG-TDF-FTC • Adherence (amongretained) 87% • Amongretained: viral supression 95% • Retentionaffectedby: • Drug and alcohol abuse • Police harassment • Butalsobylackof: • familysupport • stable housing • workopportunities • long-termgoals Frola C et al. HIV retention in TGW: TransVIIVStudy. In Press TUPDD0106. Aristegui et al. Police harassment and alcohol and drug abuse is associated with poorer 6 months retention among transgender women starting ART in a clinical trial in Argentina.

16. Challengingretention • Noemi firstwent to the hospital at age 22, whenshewastakentotheEmergencyRoomdue to fever and cough. Shewasdiagnosedwith TB, & therapid HIV test was positive. • Shestarted HRZE, B6 and TMP/SMX and DTG (BID) plus TDF/FTC 3 weekslater Felt well, decided to travel for sex-work 1000 500 100 0

17. Challengingretention • Noemi firstwent to the hospital at age 22, whenshewent to theEmergencyRoomdue to fever and cough. Shewasdiagnosedwith TB, & therapid HIV test was positive. • Shestarted HRZE, B6 and TMP/SMX and DTG (BID) plus TDF/FTC 3 weekslater Depression, need of GA therapies Felt well, decided to travel for sex-work Unstable housing, drug abuse 1000 500 100 0

18. Challengingretention • Noemi firstwent to the hospital at age 22, whenshewent to theEmergencyRoomdue to fever and cough. Shewasdiagnosedwith TB, & therapid HIV test was positive. • Shestarted HRZE, B6 and TMP/SMX and DTG (BID) plus TDF/FTC 3 weekslater Depression, need of GA therapies Felt well, decided to travel for sex-work Unstable housing, drug abuse 1000 500 100 0

19. Challengingretention • Noemi firstwent to the hospital at age 22, whenshewent to theEmergencyRoomdue to fever and cough. Shewasdiagnosedwith TB, & therapid HIV test was positive. • Shestarted HRZE, B6 and TMP/SMX and DTG (BID) plus TDF/FTC 3 weekslater Depression, need of GA therapies Felt well, decided to travel for sex-work Unstable housing, drug abuse 1000 500 100 0

20. Top 5 Health Concerns of HIV+ trans people, in order • Gender-affirming and non-discriminatory care • Hormone therapy and side effects • Mental health care, including trauma • Personal care, eg. nutrition • Antiretroviral therapy Poteat T, Positively Trans Survey, 2016 If HIV primary care provider was hormone prescriber, TGW were 3 times more likely to: • Have a visit in the previous 6 months • Have an undetectable viral load Chung Cecilia, 2016 TG Law Center

21. 25% obtained GA hormones outside the medical system 47% substance abuse 51% alcohol abuse 40% took treatments differently due to DDI concerns: 12% modified ART 12% changed doses of hormones 16% modified both treatments 51% did not discuss these concerns with their providers

23. Continuation

25. Cardiovascular risk among aging TGW • TGW suffer more frequently from cardiovascular disease than cis-women • 5% of TGW experienced venous thrombosis and/or pulmonary embolism during hormone therapy. • Prevalence of cerebrovascular disease was higher in trans women than in the control group of men • TGW experienced more myocardial infarctions than the control women, but a similar proportion compared with the control men. • Risks: • Ethinyl estradiol and equine steroids • Smoking • Dyslipidemia Gooren LJ, Wierckx K, Giltay EJ (2014) Cardiovascular disease in transsexual persons treated with cross-sex hormones: reversal of the traditional sex difference in cardiovascular disease pattern. Eur J Endocrinol 170:809–819 Wierckx K, Elaut E, Declercq E, Heylens G, De Cuypere G, Taes Y, Kaufman JM, T’Sjoen G (2013) Prevalence of cardiovascular disease and cancer during cross-sex hormone therapy in a large cohort of trans persons: a case-control study. Eur J Endocrinol 169:471–478.

26. Bone Mineral Density in TGW Compared with matched control men, TGW have: • Less muscle mass • Less strength • Lower 25-OH vitamin D • Higher prevalence of osteoporosis (16%) (at the hip, femoral neck, total body and lumbar spine) • Smaller cortical bone size • Decreased bone turnover. Possible causes: • Lower physical activity and sun exposure • Androgen blockers • Unbalanced unsupervised hormonal treatment What this means for ARV treatment? Van Caenegem E et al, CurrOpinEndocrinol Diabetes Obes. 2015; Lapauw B et al, Bone 2008

27. Tenofovir, PrEP and Hormonal Therapies • The iPREX study could not show efficacy among TGW (HR:1.1) • STIs, cocaine, methamphetamines, and high doses of hormonal therapies may impact pharmacokinetics/pharmacodynamics • High doses of estradiol might increase in vitro activity of 5’nucleotidase enzymes, and this can increase dATP and/or decrease TFVdp Lack of adherence was the proposed as the cause of this lack of efficacy. Those TGW using hormones were the most not adherent Deutsch MB et al. HIV pre-exposure prophylaxis in transgender women: a subgroup analysis of the iPrEx trial. Lancet HIV 2015

28. TGW might have lower TDF rectal concentration • In TGW, the median TFVdp:dATP was 7-fold lower in rectal tissue (but not PBMCs) • TGW exhibited 68% lower rectal TFVdp concentrations when compared to cisgender MSM, but dATP was not measured • Thai cohort shows small plasma TFV reductions (13-27%) Future studies are needed to understand the potential impact of estrogens and anti-androgen drugs on TDF, TAF & cabotegravir Cottrell ML et al. Decreased tenofovir diphosphate concentrations in a TG female cohort: Implications for HIV PrEP. CID 2019. Shieh E, et al. TGW on Estrogen Have Significantly Lower TDF/FTC Concentrations During DOT compared to Cis Men. HIVR4P. Madrid, 2018. Hiransuthikul, et al. DDI between the use of feminizing hormone therapy and PrEP among TGW: The iFACT study. AIDS2018. Amsterdam, 2018.

29. In conclusion: Put GA at the center of HIV prevention and treatment continuum ofcare Multipleapproaches are neededtoretainchallenging TGW Risk and vulnerability to HIV and STD Testing modality Retention in testing Incidence PrEP Negative Access to care Models of care GENDER AFFIRMATION Positive Burden of diseases Burden of diseases Prevalence Re-enrollment Treatment Retention Prevalence Re-enrollment Treatment Retention Gómez-Gil E, et al. Psychoneuroendocrinology 2011 Gorin-Lazard A, et al. J Sex Med. 2012 Feb;9(2):531–41

30. Muchas gracias Nadir Cardozo Solange Fabián Mariana Duarte Claudia Frola Inés Aristegui Virginia Zalazar Pablo Radusky Marcela Romero omar.sued@huesped.org.ar … and toall staff, volunteers and collaboratorsof Fundación Huésped. Thanksalsotoallthe TGW thatworkeverydayto be included and to Paul Kerstonforthe English edition.