Transgender and gender-nonbinary (trans/GNB) individuals are disproportionally affected by HIV, yet they are not adequately represented in HIV research. By engaging trans/GNB individuals in research designed to address their needs, we can inform evidence-based care and advance healthcare.
Keywords: HIV research, transgender, gender non binary, inclusion
Abstract
Transgender and gender-nonbinary (trans/GNB) individuals are disproportionally affected by human immunodeficiency virus (HIV), yet they are not adequately represented in HIV research and often underserved in clinical care. By building on community strengths and addressing structural, psychological and biological challenges, we can improve the engagement of trans/GNB people in research and ultimately improve prevention, testing, and care for this population. Here, we review the current state of the science related to HIV for trans/GNB people and discuss next steps to expand research that aims to improve the lives and well-being of trans/GNB persons.
Transgender and gender-nonbinary (trans/GNB) individuals are disproportionally affected by human immunodeficiency virus (HIV) and experience unique health challenges and disparities [1], yet they are not sufficiently represented in HIV research [2–4]. For example, since the beginning of the HIV epidemics, HIV risk and care data from transgender women have been routinely merged with data from men who have sex with men (MSM) [1], and gender identity information has been inadequately documented. These decisions have long masked the real burden of HIV among trans/GNB persons.
While the World Professional Association for Transgender Health (WPATH) has published separate medical care guidelines for trans/GNB people since 1979 [5], disparities in caring for these patients continue to exist. In the 2010 National HIV/AIDS strategy, trans/GNB individuals were mentioned as a target high-risk population for HIV prevention [6]. In 2013 the US President’s Emergency Plan for AIDS Relief (PEPFAR) designated trans/GNB people as a “key population” for HIV risk, independent from MSM [7]. The World Health Organization (WHO) issued for the first time separate recommendations for trans/GNB populations within its HIV guidelines in 2014 (which were updated in 2016 [8], based on the transgender implementation tool [9]). Furthermore, the National Institutes of Health (NIH) and its clinical research networks have recently developed a number of strategies to engage trans/GNB individuals in NIH-funded HIV/AIDS clinical trials [10].
Despite these important steps forward, there is more work to be done. While trans/GNB individuals share many of the same needs as the general population, they also have unique medical needs to increase gender alignment, such as gender-affirming hormone therapy and surgeries [11]. Many psychosocial factors contribute to their marginalization including exposure to enacted and felt stigma [12], violence, and discrimination [13–16]. All of these factors should be considered when conducting research in these populations, as they impact recruitment, retention, and outcomes.
LANGUAGE FOR TRANSGENDER AND GENDER-NONBINARY PEOPLE
While the language used to describe trans/GNB people is being continually refined and improved, it is crucial to use terminology that is respectful, nonpathologizing, and consistent with the complex social and cultural framework of the trans/GNB community [17]. Terms such as “sex” and “gender” are linked, but they are not synonyms. The word “sex” is used to refer to the physical/biological differences between male and female, while the word “gender” is used in connection to the behavior and cultural practices of men and women. Importantly, “gender” is a spectrum and is not limited to 2 possibilities (male or female) but includes “nonbinary” and “fluid” identities, among others. It is important to understand and appropriately distinguish concepts such as gender identity, expression, sex, and sexual orientation (Figure 1). To best address and engage the trans/GNB population in research, a knowledge of the appropriate terminology and the gender spectrum is required. WPATH provides specific guidelines to facilitate clear and respectful communication with trans/GNB individuals [5, 18]. Researchers are encouraged to follow WPATH’s guidelines when interacting with the trans/GNB community and use detailed, precise, and scientifically based language when presenting their work in papers and scientific conferences.
Figure 1.
Summary of terminology and definitions.
STUDY DESIGN AND METHODOLOGY
Trans/GNB individuals constitute an important focus for HIV research, but studies in this population present unique methodologic and implementation challenges [19]. Various methods have been used, each with its advantages and limitations (reviewed in [3]). For example, population-based studies are powerful but require data sources (eg, Department of Motor Vehicles, voter registration lists) to collect information on gender beyond binary “sex” categories. Electronic medical records offer easy access to comprehensive data (eg, Veterans Health Administration, health maintenance organizations) but will miss key subgroups (eg, uninsured or not engaged in healthcare). Clinic-based approaches offer excellent opportunities for in-depth data collection, specimen acquisition, and access to various trans/GNB subgroups; however, putting together a sufficient cohort requires including multiple sites, which is resource intensive and may introduce potential confounding biases [19]. Other methods, such as venue-based approaches, respondent-driven sampling, or internet-based recruitment cannot offer generalizable results and often have poor retention rates [20]. Implementing appropriate study designs and sampling strategies is crucial to address key research questions unique to trans/GNB people [3]. Additionally, it is important to define the target research population within the gender spectrum, select appropriate controls, and define endpoints while taking into account the mentioned limitations.
OUTREACH AND RECRUITMENT
The trans/GNB population is particularly hard to reach and engage in research activities [21]. A lack of legal recognition, active criminalization, and lack of protection against employment and housing discrimination in most countries contribute to their marginalization [16, 22]. Developing strategies to engage and link this population to appropriate research activities is an urgent priority and will require case management or client-centered care above and beyond the usual retention efforts.
To successfully recruit and retain trans/GNB individuals, all research personnel should be educated and trained about trans/GNB unique issues. Providers and research staff who routinely engage in research with MSM may not be adequately equipped to interact with the trans/GNB community [23]. Similarly, research studies designed for MSM do not always fit the priorities of the trans/GNB population. In fact, many psychosocial drivers of HIV risk among transwomen are similar to those of cisgender (cis-) women, such as intimate partner violence, sex work, misogyny, less power to negotiate safe sex, and body shaming [23, 24]. If resources are not available to develop a trans/GNB-specific program, then research opportunities should be offered to transwomen as they are for cis-women rather than MSM, and similarly for transmen [25]. Because trans/GNB individuals often prioritize hormonal therapy [16], engaging trans/GNB individuals in HIV research opportunities at the time and location of gender-affirming medical care will provide synergistic results [26]. Ultimately, the passage and enforcement of legislation that protects trans/GNB people against discrimination in public accommodations, including healthcare settings, represents a critical structural intervention to reduce health inequities and will facilitate outreach, enrollment, and retention in research studies.
TRANSGENDER AND GENDER-NONBINARY PREVALENCE
Assessing the impact of HIV research on trans/GNB individuals will require better knowledge of their representation within the population. Recent meta-analyses reported an estimated population size of 390–560 trans/GNB adults per 100000 in the United States (0.4%–0.6%), or 1–1.4 million adults nationally [27, 28] but this is likely an underestimate, as most official records do not report consistent data on gender identity. To obtain precise data, the use of the “2-step method” for the collection of gender identity is recommended, which includes both gender identity and birth-assigned sex [29–31]. Trans/GNB people can be identified as those whose gender identity differs from their birth-assigned sex. This method is superior to a single question querying gender/sex with choices of “male,” “female,” and “transgender,” as some trans/GNB individuals may choose “male” or “female” based on how they identify, resulting in effective invisibility of their transgender status [31, 32].
HUMAN IMMUNODEFICIENCY VIRUS PREVALENCE AMONG TRANSGENDER AND GENDER-NONBINARY INDIVIDUALS
Data on prevalence and incidence of HIV in the trans/GNB population are not well documented. Compared with all adults of reproductive age, transwomen have almost 50 times the odds of HIV infection [1], with yearly incidence rates between 3.5% and 8%, which are even higher for those engaged in sex work [16]. The Centers for Disease Control and Prevention (CDC) currently estimates that one-quarter of all transwomen in the United States are HIV infected, and half of all transwomen diagnosed with HIV are black/African American [33]. Since black/African Americans represent a small fraction of all trans/GNB individuals in the United States, the disparity is evident [34].
The prevalence of HIV among transmen is significantly lower (0–3%), but transmen who have sex with cis-MSM are also at substantial risk for acquiring HIV [35, 36]. Figure 2 summarizes the most recent epidemiological data for the trans/GNB population in the United States.
Figure 2.
Summary of recent epidemiological data for the transgender/gender-nonbinary population in the United States. Abbreviations: CDC, Centers for Disease Control and Prevention; HIV, human immunodeficiency virus.
Unfortunately, many trans/GNB people living with HIV are not aware of their HIV status or are not included in the statistics, so these numbers are likely underestimated. There is also variability of HIV risk and scientific knowledge across the various gender subgroups. Thus, future research studies should collect data specific for transmen vs transwomen vs nonbinary genders, with consideration of those who do not identify as feminine or masculine or who integrate both.
HUMAN IMMUNODEFICIENCY VIRUS PREVENTION IN TRANSGENDER AND GENDER-NONBINARY INDIVIDUALS
There is growing commitment in public health to understand and improve the health of trans/GNB individuals. As mentioned above, many trans/GNB people live in contexts of social discrimination, lack of legal recognition, and exclusion from employment and educational opportunities [22]. These social determinants can undermine their sexual relationships and limit their ability to pursue safe and effective HIV prevention. Trans/GNB individuals often report having multiple sexual partners, engaging in sex work for survival, and using recreational drugs, all of which are associated with increased risk of HIV acquisition and transmission [37]. A recent study showed that about 70% of transmen attributed new sexual behaviors and increased frequency of sexual activity to testosterone use [38]. While social and behavioral factors are crucial, the biology associated with HIV transmission in the trans/GNB population is understudied. For example, little is known about how hormonal therapy might affect HIV transmission and preexposure prophylaxis (PrEP) or how HIV and various drugs penetrate neovaginal tissue.
The effectiveness of PrEP in trans/GNB individuals is a particularly important question, which requires attention [19]. Even though Truvada (emtricitabine and tenofovir disoproxil) is currently indicated for use broadly in the trans/GNB population, more studies are needed to determine current efficacy, barriers to use, and effectiveness. Pharmacokinetic studies have shown no evidence of drug–drug interaction between Truvada and oral contraception in cis-women; similarly, clinical trials have shown no decrease in efficacy of hormone-based contraception (oral pills, injections, or implants) in cis-women taking PrEP [39, 40]. While these data are reassuring, no formal pharmacological interaction study has been performed in trans/GNB individuals on PrEP and hormonal therapy [25].
The original pre-exposure prophylaxis initiative clinical trial [41] described only 1% of their participants as transgender; on a subsequent reanalysis after reclassifying participants (according to self-reported gender identity, different gender than at birth or men taking feminizing hormones), the authors reported up to 14% of their participants as transgender, mostly within non-US sites [42]. In this secondary analysis, there was no difference in efficacy between the PrEP and placebo arms for trans/GNB people. However, among the active PrEP arm, the drug was detected in only about 18% of the trans/GNB participants, a lower proportion than the overall group, suggesting lower adherence among trans/GNB individuals.
Prospective studies are needed to evaluate PrEP efficacy and drug levels in combination with various hormonal therapy. To address some of these issues, in 2016 the California HIV Research Program funded the first large-scale PrEP demonstration projects specifically for trans/GNB populations, which are currently ongoing [43].
HUMAN IMMUNODEFICIENCY VIRUS CARE
Trans/GNB people living with HIV/AIDS face unique psychosocial challenges that complicate access and adherence to HIV care. Trans/GNB people living with HIV/AIDS are less likely to be on antiretroviral therapy (ART) [44] and demonstrate lower medication adherence than cisgender individuals [45]. They often report less confidence in their abilities to integrate treatment regimens into their daily lives [46]. A study evaluating the care continuum among newly diagnosed transwomen in San Francisco found that, compared to the general population, 77% were linked to primary care within 3 months of their HIV diagnosis (vs 85%), 65% were taking ART (vs 83%–89%), and only 44% achieved virological suppression (vs 50%) [47, 48]. While differences exist between studies, the low rate of virological suppression among trans/GNB people has important public health implications and amplify HIV transmission between HIV-positive trans/GNB people and their partners.
Concerning comorbidities associated with HIV, current research suggests an increased mortality in trans/GNB individuals as compared to cisgender persons, and a modest increase in cardiovascular risk and osteoporosis related to hormonal therapy in transwomen [4, 49]. Future longitudinal studies should be performed to consider the impact of HIV on mortality and morbidity in combination with the effects of mental health, as well as gender-affirming medical and surgical interventions.
HORMONE THERAPY AND ANTIRETROVIRAL THERAPY
Hormonal therapy is an important aspect of gender-affirming care used as part of medical transition [50]. Concerns about adverse interactions between ART and hormonal therapy are frequent among the trans/GNB population. Studies have shown reduced ART compliance in transwomen with HIV due to concerns that ART will decrease the effects of hormonal therapy [51]. There are no studies on the pharmacokinetics or pharmacodynamics of ART use in trans/GNB individuals using feminizing or masculinizing hormones, and all data on drug–drug interactions are extrapolated from oral contraceptives in cis-women or testosterone therapy for cis-men with hypogonadism [52–56]. Furthermore, use of progesterone and anti-androgens, such as spironolactone, cyproterone acetate, and gonadotropin-releasing hormone agonists, is frequent among trans/GNB individuals, and few to no pharmacokinetic data are available on the impact of ART and these medications [57].
Generally, HIV and its treatment are not contraindications to hormonal therapy and based on available data in cis-women, most ART regimens can be combined safely with estrogens (with the exception of amprenavir, unboosted fosamprenavir, and stavudine, which are not part of modern ART regimens) [58]. Similarly, testosterone replacement in cis-men with hypogonadism on ART has shown to be safe and to improve quality of life [59]. Overall, providing hormonal therapy in the context of HIV care improves engagement, retention in care, and adherence [23, 46]. Clinicians should remain vigilant about possible interactions and have an open dialogue with their trans/GNB patients. More research is needed to understand how to best deliver hormonal therapy with ART.
HORMONE THERAPY, THE VIRUS, AND THE IMMUNE SYSTEM
Hormonal therapy for gender affirmation may impact HIV transmission and disease progression. Most research has focused on estrogen and progesterone used by cis-women and is conflicting [60]. Studies have shown both increased and decreased HIV transcription due to effects of 17-β estradiol, while others showed reduced susceptibility of CD4+ T cells mediated by estradiol [61–63]. Both endogenous and exogenous estrogen (in oral contraception) are mainly protective against HIV transmission by reducing the frequency of HIV target cells, inflammatory T cells, and macrophages in the vaginal epithelial and stromal tissues, whereas progesterone seems to increase risk of HIV transmission by enhancing the expression of HIV target cells and recruitment of inflammatory cells in the vaginal epithelium [64]. In vitro studies demonstrated direct associations between estrogen-dominant states and decreased HIV transcription and replication, mediated by estrogen receptor α- and β-catenin-dependent mechanisms [61, 65].
Little is known about the effects of testosterone on HIV replication or disease progression in transmen as most available data derive from HIV-infected cis-men who are on testosterone replacement for hypogonadism [56, 66]. One study investigated the effects on body composition and strength of physiologic testosterone replacement in cis-women living with HIV/AIDS, and showed no adverse effects on HIV replication or CD4+ counts, albeit the target testosterone levels were much lower than traditionally used in trans/GNB patients [67].
To date, there are no specific studies on the effects of exogenous testosterone, estradiol, or antiandrogens at the doses typically used in trans/GNB patients on HIV transmission or disease progression. The guidelines to provide hormonal therapy for trans/GNB individuals are not well standardized. For example, transwomen can use estradiol patches, tablets, and injections in various doses as well as different androgen blockers. This void in scientific knowledge creates a challenge in preventing and treating HIV infection in the trans/GNB population. Future research should focus on the effects of the various doses, formulations, and combinations of hormonal therapy on viral transmission and suppression specifically in trans/GNB individuals.
HUMAN IMMUNODEFICIENCY VIRUS RESERVOIR AND BARRIERS FOR ERADICATION
It is likely that hormonal therapy has implications regarding HIV persistence and eradication. Estrogens at physiologic levels are strong inhibitors of HIV transcription [61, 68]. A recent study provided evidence that estradiol may inhibit HIV transcriptional reactivation in a sex-specific manner, but it is unclear how this mechanism might affect HIV persistence in trans/GNB individuals taking estrogen-based hormonal therapy. In particular, agents that are designed for “kick and kill” strategies may be impacted by estradiol-mediated mechanisms. Regarding HIV cure efforts, it is possible that estrogens may make HIV eradication both more difficult (diminishing the “kick” effect by inhibiting transcription) and less difficult (smaller reservoir due to decreased ongoing replication). The effect of other hormones (eg, progesterone, anti-androgens) on HIV persistence has not been systemically investigated, and future studies should consider these factors when designing HIV eradication strategies that are applicable across the spectrum of gender.
CALL TO ACTION TO INCLUDE MORE TRANSGENDER AND GENDER-NONBINARY INDIVIDUALS IN HUMAN IMMUNODEFICIENCY VIRUS RESEARCH
Trans/GNB individuals have disproportionately experienced discrimination in most aspects of their lives, including within the medical community. Trans/GNB people experience multiple obstacles when attempting to access adequate primary healthcare [11]. Many trans/GNB people who report bad experiences in the medical setting and do not get treated appropriately might also express apprehension in becoming part of research studies.
To explore barriers and facilitators to enrollment of transwomen in clinical trials, the HIV Vaccine Trials Network conducted focus groups of transwomen in 4 urban areas [69]. Recognized barriers included (1) stigma, (2) misinformation, (3) feeling excluded from research, (4) mistrust in the scientific community, and (5) possible side effects. Facilitators included (1) increased information and awareness, (2) culturally competent research staff, (3) recommendation from a trusted trans-friendly healthcare provider, and (4) assistance with basic needs. While these data are limited to transwomen in US metropolitan areas, they do suggest that reducing discrimination and ensuring access to culturally competent and high-quality research opportunities is a priority (Figure 3).
Figure 3.
Summary of suggested steps necessary to create a gender-affirming healthcare and research environment. See also “Stepping up: a Consensus Statement by Trans Leaders” (https://www.aidsunited.org/resources/stepping-up-a-consensus-statement-by-trans-leaders?docid=79). Abbreviations: GNB, gender nonbinary.
Including all key populations, such as trans/GNB people, in research studies and offering culturally appropriate research opportunities is not only important for scientific advancement, but it also empowers the populations being studied. There is a growing demand within the scientific and trans/GNB community to increase resources to engage people across the gender spectrum in research. It is essential that the trans/GNB community be involved in the planning and implementation of research efforts and clinical studies that affect them. A coordinated, collaborative approach that integrates health and human rights is integral to addressing the needs and cultural barriers of trans/GNB research and ensuring that all populations will be effectively represented in future research efforts. By appropriately engaging trans/GNB individuals in research designed to address their needs, we can inform evidence-based care and advance the healthcare of trans/GNB people worldwide.
Notes
Author contributions. S. G., J. S. H., J. B., B. S., and D. M. S. participated in creating the outline design, performed the literature search, and wrote the primary version of the manuscript. All authors read and approved the final manuscript.
Disclaimer. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Financial support. This work was supported primarily by a grant from the National Institutes of Health (NIH), University of California, San Francisco–Gladstone Institute of Virology and Immunology Center for AIDS Research (grant number P30-AI027763, Creative and Novel Ideas in HIV Research); California HIV Research Program Idea award to S. G.; the Department of Veterans Affairs Grant KL2TR001444 of CTSA; the James B. Pendleton Charitable Trust; and the NIH (grant numbers AI100665, MH100974, MH097520, DA034978, AI007384, AI027763, AI106039, AI43638, AI074621, AI036214, MH101012, UL1TR000100, CARE U19 AI096113, AI134295, HD094646, and AI068636-09).
Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
References
- 1. Baral SD, Poteat T, Strömdahl S, Wirtz AL, Guadamuz TE, Beyrer C. Worldwide burden of HIV in transgender women: a systematic review and meta-analysis. Lancet Infect Dis 2013; 13:214–22. [DOI] [PubMed] [Google Scholar]
- 2. Reisner SL, Poteat T, Keatley J et al. Global health burden and needs of transgender populations: a review. Lancet 2016; 388:412–36. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Reisner SL, Deutsch MB, Bhasin S et al. Advancing methods for US transgender health research. Curr Opin Endocrinol Diabetes Obes 2016; 23:198–207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Feldman J, Brown GR, Deutsch MB et al. Priorities for transgender medical and healthcare research. Curr Opin Endocrinol Diabetes Obes 2016; 23:180–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Coleman E, Bockting M, Botzer P. Standards of care for the health of transsexual, transgender, and gender-nonconforming people, version 7. Int J Transgender 2012; 13:165–232. [Google Scholar]
- 6. National HIV/AIDS Strategy. Available at: https://www.hiv.gov/federal-response/national-hiv-aids-strategy/overview. Accessed September 2017.
- 7. United States President’s Emergency Plan for AIDS Relief. Key populations: ensuring human rights and leaving no one behind Available at: https://www.pepfar.gov/priorities/keypopulations/index.htm. Accessed April 2017.
- 8. World Health Organization, Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations: 2016 update Available at: http://apps.who.int/iris/bitstream/10665/246200/1/9789241511124-eng.pdf?ua=1. Accessed October 2017. [PubMed]
- 9. World Health Organization, Implementing comprehensive HIV and STI programmes with transgender people: practical guidance for collaborative interventions 2016. Available at: http://www.undp.org/content/dam/undp/library/HIV-AIDS/Key populations/TRANSIT.pdf. Accessed October 2017.
- 10. Siskind RL, Andrasik M, Karuna ST et al. Engaging transgender people in NIH-funded HIV/AIDS clinical trials research. J Acquir Immune Defic Syndr 2016; 72(Suppl 3):S243–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Thomas R, Pega F, Khosla R, Verster A, Hana T, Say L. Ensuring an inclusive global health agenda for transgender people. Bull World Health Organ 2017; 95:154–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. White Hughto JM, Reisner SL, Pachankis JE. Transgender stigma and health: a critical review of stigma determinants, mechanisms, and interventions. Soc Sci Med 2015; 147:222–31. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Nuttbrock L, Bockting W, Rosenblum A et al. Gender abuse, depressive symptoms, and HIV and other sexually transmitted infections among male-to-female transgender persons: a three-year prospective study. Am J Public Health 2013; 103:300–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Winter S, Diamond M, Green J et al. Transgender people: health at the margins of society. Lancet 2016; 388:390–400. [DOI] [PubMed] [Google Scholar]
- 15. James SE, Herman JL, Rankin S, Keisling M, Mottet L, Analfi M.. The report of the 2015 U.S. Transgender Survey. Washington, DC: National Center for Transgender Equality, 2016. [Google Scholar]
- 16. Grant JM, Mottet LA, Tanis J, Min D.. National transgender discrimination survey report on health and health care. 2010. Available at: https://www.transequality.org/sites/default/files/docs/USTS-Full-Report-FINAL.PDF. Accessed September 2017.
- 17. Bouman WP, Schwend AS, Motmans J et al. Language and trans health. Int J Transgend 2017; 18:1–6. [Google Scholar]
- 18. Reisner SL, Bailey Z, Sevelius J. Racial/ethnic disparities in history of incarceration, experiences of victimization, and associated health indicators among transgender women in the U.S. Women Health 2014; 54:750–67. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Hughes JP, Emel L, Hanscom B, Zangeneh S. Design issues in transgender studies. J Acquir Immune Defic Syndr 2016; 72(Suppl 3):S248–51. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. McCreesh N, Frost SD, Seeley J et al. Evaluation of respondent-driven sampling. Epidemiology 2012; 23:138–47. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Del Rio C. HIV infection in hard-to-reach populations. Top Antivir Med 2016; 24:86–9. [PMC free article] [PubMed] [Google Scholar]
- 22. Reisner SL, Hughto JM, Dunham EE et al. Legal protections in public accommodations settings: a critical public health issue for transgender and gender-nonconforming people. Milbank Q 2015; 93:484–515. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. Sevelius JM, Patouhas E, Keatley JG, Johnson MO. Barriers and facilitators to engagement and retention in care among transgender women living with human immunodeficiency virus. Ann Behav Med 2014; 47:5–16. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Machtinger EL, Haberer JE, Wilson TC, Weiss DS. Recent trauma is associated with antiretroviral failure and HIV transmission risk behavior among HIV-positive women and female-identified transgenders. AIDS Behav 2012; 16:2160–70. [DOI] [PubMed] [Google Scholar]
- 25. Sevelius JM, Deutsch MB, Grant R. The future of PrEP among transgender women: the critical role of gender affirmation in research and clinical practices. J Int AIDS Soc 2016; 19:21105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. Ickovics JR. “Bundling” HIV prevention: integrating services to promote synergistic gain. Prev Med 2008; 46:222–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Meerwijk EL, Sevelius JM. Transgender population size in the United States: a meta-regression of population-based probability samples. Am J Public Health 2017; 107:e1–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Flores AR, Herman JL, Gates GJ, Brown TNT.. How many adults identify as transgender in the United States? Los Angeles, CA: The Williams Institute, 2016. [Google Scholar]
- 29. Deutsch MB, Buchholz D. Electronic health records and transgender patients–practical recommendations for the collection of gender identity data. J Gen Intern Med 2015; 30:843–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Cahill S, Singal R, Grasso C et al. Do ask, do tell: high levels of acceptability by patients of routine collection of sexual orientation and gender identity data in four diverse American community health centers. PLoS One 2014; 9:e107104. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Tate CC, Ledbetter JN, Youssef CP. A two-question method for assessing gender categories in the social and medical sciences. J Sex Res 2013; 50:767–76. [DOI] [PubMed] [Google Scholar]
- 32. Gender Identity in U.S. Surveillance Group. Best practices for asking questions to identify transgender and other gender minority respondents on population-based surveys Available at: http://williamsinstitute.law.ucla.edu/wp-content/uploads/geniuss-report-sep-2014.pdf. Accessed September 2017.
- 33. Centers for Disease Control and Prevention. HIV among transgender people Atlanta, GA: CDC, 2014. [Google Scholar]
- 34. Herbst JH, Jacobs ED, Finlayson TJ et al. Estimating HIV prevalence and risk behaviors of transgender persons in the United States: a systematic review. AIDS Behav 2008; 12:1–17. [DOI] [PubMed] [Google Scholar]
- 35. Rowniak S, Chesla C, Rose CD, Holzemer WL. Transmen: the HIV risk of gay identity. AIDS Educ Prev 2011; 23:508–20. [DOI] [PubMed] [Google Scholar]
- 36. Reisner SL, White Hughto JM, Pardee D, Sevelius J. Syndemics and gender affirmation: HIV sexual risk in female-to-male trans masculine adults reporting sexual contact with cisgender males. Int J STD AIDS 2016; 27:955–66. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Reisner SL, White JM, Mayer KH, Mimiaga MJ. Sexual risk behaviors and psychosocial health concerns of female-to-male transgender men screening for STDs at an urban community health center. AIDS Care 2014; 26:857–64. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38. Dadasovich R, Auerswald C, Minnis AM, Raymond HF, McFarland W, Wilson EC. Testosterone and sexual risk among transmen: a mixed methods exploratory study. Cult Health Sex 2017; 19:256–66. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39. Murnane PM, Heffron R, Ronald A et al. ; Partners PrEP Study Team. Pre-exposure prophylaxis for HIV-1 prevention does not diminish the pregnancy prevention effectiveness of hormonal contraception. AIDS 2014; 28:1825–30. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40. Kearney BP, Mathias A. Lack of effect of tenofovir disoproxil fumarate on pharmacokinetics of hormonal contraceptives. Pharmacotherapy 2009; 29:924–9. [DOI] [PubMed] [Google Scholar]
- 41. Grant RM, Lama JR, Anderson PL et al. ; iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010; 363:2587–99. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42. Deutsch MB, Glidden DV, Sevelius J et al. ; iPrEx Investigators. HIV pre-exposure prophylaxis in transgender women: a subgroup analysis of the iPrEx trial. Lancet HIV 2015; 2:e512–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43. California HIV/AIDS Research Program. Strategic initiatives: epidemic interventions initiative Available at: http://chrp.yes4yes.com/initiatives_programs/epidemic-intervention.html. Accessed April 2017.
- 44. 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. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45. Sevelius JM, Carrico A, Johnson MO. Antiretroviral therapy adherence among transgender women living with HIV. J Assoc Nurses AIDS Care 2010; 21:256–64. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46. Sevelius JM, Saberi P, Johnson MO. Correlates of antiretroviral adherence and viral load among transgender women living with HIV. AIDS Care 2014; 26:976–82. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47. Santos GM, Wilson EC, Rapues J, Macias O, Packer T, Raymond HF. HIV treatment cascade among transgender women in a San Francisco respondent driven sampling study. Sex Transm Infect 2014; 90:430–3. [DOI] [PubMed] [Google Scholar]
- 48. San Francisco Department of Public Health. HIV/AIDS epidemiology annual report 2012. HIV epidemiology section 2013. Available at: https://www.sfdph.org/dph/comupg/oprograms/hivepisec/HIVepiSecReports.asp. Accessed September 2017.
- 49. Van Caenegem E, Taes Y, Wierckx K et al. Low bone mass is prevalent in male-to-female transsexual persons before the start of cross-sex hormonal therapy and gonadectomy. Bone 2013; 54:92–7. [DOI] [PubMed] [Google Scholar]
- 50. Hembree WC, Cohen-Kettenis PT, Gooren L et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2017;102:3869–903. [DOI] [PubMed] [Google Scholar]
- 51. Braun HM, Candelario J, Hanlon CL et al. Transgender women living with HIV frequently take antiretroviral therapy and/or feminizing hormone therapy differently than prescribed due to drug-drug interaction concerns. LGBT Health 2017; 4:371–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52. El-Ibiary SY, Cocohoba JM. Effects of HIV antiretrovirals on the pharmacokinetics of hormonal contraceptives. Eur J Contracept Reprod Health Care 2008; 13:123–32. [DOI] [PubMed] [Google Scholar]
- 53. Blick G, Khera M, Bhattacharya RK, Kushner H, Miner MM. Testosterone replacement therapy in men with hypogonadism and HIV/AIDS: results from the TRiUS registry. Postgrad Med 2013; 125:19–29. [DOI] [PubMed] [Google Scholar]
- 54. Radix A, Sevelius J, Deutsch MB. Transgender women, hormonal therapy and HIV treatment: a comprehensive review of the literature and recommendations for best practices. J Int AIDS Soc 2016; 19:20810. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55. Gomes AR, Souteiro P, Silva CG et al. Prevalence of testosterone deficiency in HIV-infected men under antiretroviral therapy. BMC Infect Dis 2016; 16:628. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 56. Bhatia R, Murphy AB, Raper JL et al. ; Centers for AIDS Research Network of Integrated Clinical Systems. Testosterone replacement therapy among HIV-infected men in the CFAR Network of Integrated Clinical Systems. AIDS 2015; 29:77–81. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 57. Antiretroviral Therapy Cohort Collaboration. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet 2008; 372:293–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 58. Whiteman MK, Jeng G, Samarina A et al. Associations of hormonal contraceptive use with measures of HIV disease progression and antiretroviral therapy effectiveness. Contraception 2016; 93:17–24. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 59. Bhasin S, Storer TW, Asbel-Sethi N et al. Effects of testosterone replacement with a nongenital, transdermal system, Androderm, in human immunodeficiency virus-infected men with low testosterone levels. J Clin Endocrinol Metab 1998; 83:3155–62. [DOI] [PubMed] [Google Scholar]
- 60. Ragupathy V, Devadas K, Tang S et al. Effect of sex steroid hormones on replication and transmission of major HIV subtypes. J Steroid Biochem Mol Biol 2013; 138:63–71. [DOI] [PubMed] [Google Scholar]
- 61. Szotek EL, Narasipura SD, Al-Harthi L. 17β-Estradiol inhibits HIV-1 by inducing a complex formation between β-catenin and estrogen receptor α on the HIV promoter to suppress HIV transcription. Virology 2013; 443:375–83. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 62. Katagiri D, Hayashi H, Victoriano AF, Okamoto T, Onozaki K. Estrogen stimulates transcription of human immunodeficiency virus type 1 (HIV-1). Int Immunopharmacol2006; 6:170–81. [DOI] [PubMed] [Google Scholar]
- 63. Rodriguez-Garcia M, Biswas N, Patel MV et al. Estradiol reduces susceptibility of CD4+ T cells and macrophages to HIV-infection. PLoS One 2013; 8:e62069. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 64. Hel Z, Stringer E, Mestecky J. Sex steroid hormones, hormonal contraception, and the immunobiology of human immunodeficiency virus-1 infection. Endocr Rev 2010; 31:79–97. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 65. Karn J. Estrogen blocks HIV re-emergence from latency and points to gender-specific differences in HIV reservoirs. In: International AIDS Society 2015: Towards an HIV Cure Symposium, Vancouver. [Google Scholar]
- 66. Rochira V, Guaraldi G. Hypogonadism in the HIV-infected man. Endocrinol Metab Clin North Am 2014; 43:709–30. [DOI] [PubMed] [Google Scholar]
- 67. Choi HH, Gray PB, Storer TW et al. Effects of testosterone replacement in human immunodeficiency virus-infected women with weight loss. J Clin Endocrinol Metab 2005; 90:1531–41. [DOI] [PubMed] [Google Scholar]
- 68. Abdel-Mohsen M, Wang C, Strain MC et al. Select host restriction factors are associated with HIV persistence during antiretroviral therapy. AIDS 2015; 29:411–20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 69. Andrasik MP, Yoon R, Mooney J et al. ; HVTN 505 Study Team; NIAID HIV Vaccine Trials Network. Exploring barriers and facilitators to participation of male-to-female transgender persons in preventive HIV vaccine clinical trials. Prev Sci 2014; 15:268–76. [DOI] [PMC free article] [PubMed] [Google Scholar]