General guidelines for HIV screening, prevention, and care do not differ for transgender people; however, HIV services for transgender people should address the specific biological, psychological, and social needs of this population. HIV prevention and care programs adapted from practices developed for non-transgender men who have sex with men (MSM) or for non-transgender women fail to address the unique structural factors and inequities that increase HIV risk and produce barriers to care among transgender people. For example, many trans women (especially young adults, racial/ethnic minorities and undocumented individuals) experience intersecting discrimination and high rates of trauma, unstable housing, poverty, incarceration, and unemployment, which all negatively impact HIV risk, testing, and continuing care.
Antiretroviral treatment (ART) recommendations for transgender women using feminizing hormones are complicated by lack of data on forms of estrogen commonly used for gender affirming hormone therapy; therefore there is a need to extrapolate data on drug-drug interactions from studies using combination oral contraceptives. Little data exist on HIV among transgender men, likely due to much lower HIV prevalence. However, evidence for HIV risk among transgender men who have sex with men is growing.[2-4]
In line with national guidelines from the U.S. Centers for Disease Control (CDC) and the U.S. Preventive Services Task Force (USPSTF) that recommend universal screening for HIV, all transgender persons should be screened at least once for HIV. After initial screening of all patients, repeat screening is based on HIV risk assessment. Effective risk assessment requires the ability to obtain an accurate sexual history that includes anatomy-specific sexual behavior. Transgender women who have a penis should be asked about insertive intercourse as well as receptive intercourse. Transgender women and men who have a vagina should be asked about vaginal as well as anal intercourse, although the risk of HIV acquisition via receptive vaginal sex in a transgender woman who has undergone vaginoplasty is unknown. Risks associated with male genital reconstructions such as phalloplasty or metoidioplasty are unknown. Open-ended questions that do not assume the anatomy and sex or gender of partners are likely to provide the most information.
Condoms continue to be a mainstay of HIV prevention. However, using condoms may be difficult for transgender women taking feminizing hormones due to reduced tumescence. Transgender women may also lack the agency to negotiate the use of condoms during sex, especially those who engage in sex work. The role of condoms in transgender men who have undergone phalloplasty is unknown and likely depends on the specific anatomy and surgical approach used. "Female" condoms may be an option for transgender men who engage in receptive vaginal sex.
Newer biomedical HIV prevention interventions increase the options available to reduce HIV risk. There are two categories of medications currently available that are designed to be taken by people who do NOT have HIV for the purposes of preventing HIV acquisition: 1) pre-exposure prophylaxis (PrEP) and 2) non-occupational post-exposure prophylaxis (nPEP).
Pre-exposure prophylaxis (PrEP)
Daily oral PrEP with the fixed-dose combination of tenofovir disoproxil fumarate (TDF) 300 mg and emtricitabine (FTC) 200 mg has been shown to be safe and effective in reducing the risk of sexual HIV acquisition in studies with MSM, non-transgender heterosexual adults, and people who inject drugs. CDC has published detailed clinical guidelines for the use of PrEP for individuals at high risk for HIV acquisition.
A sub-analysis of data from a large multi-national randomized controlled trial of PrEP suggests that PrEP is effective in preventing HIV in transgender women when they take the medication as prescribed. However, no efficacy was found among transgender women on "intent-to-treat" analysis. Importantly, all of the transgender women who seroconverted in the PrEP arm of the study had no detectable TDF in their blood, suggesting that they did not take the medication as prescribed. There are no known drug-drug interactions between TDF/FTC and gender affirming hormones, nor are there any known contraindications to concomitant use of PrEP with gender affirming hormone therapy. To effectively engage transgender women, PrEP programs should use trans-inclusive marketing strategies, address community concerns about drug interactions between TDF and gender affirming hormones, and ensure services are delivered by a provider who is knowledgeable about trans health.
Non-occupational post-exposure prophylaxis (nPEP)
The use of nPEP in transgender people should follow guidelines as in non-transgender people. As with PrEP, social marketing and awareness campaigns should be tailored to transgender populations.
Treatment of HIV concurrent with hormone therapy
HIV and its treatment are not contraindications to hormone therapy. In fact, providing hormone therapy in the context of HIV care may improve engagement and retention in care  as well as adherence and viral load.[10,11] The World Health Organization  as well as the U.S. Department of Health and Human Services  recommend antiretroviral therapy for everyone living with HIV, regardless of HIV viral load or CD4 count.
Metabolism of estrogens occurs via the cytochrome P450 enzyme system; therefore there are potential drug-drug interactions with ART agents. Information about these interactions are based on studies in the context of contraception and typically include ethinyl estradiol rather than 17-beta estradiol recommended for feminization. Data are not available on drug interactions between hormones and ARTs in the setting of transgender care. However, based on available data, most ART can be likely used safely used with estrogen with two exceptions: Amprenavir (Agenerase) and unboosted fosamprenavir (Lexiva) are not recommended for co-administration with estrogens due to a decrease in amprenavir serum concentrations.
Limited data suggest that non-nucleoside reverse transcriptase inhibitors (NNRTIs), ritonavir (RTV)-boosted protease inhibitors (PIs), or cobicistat with integrase strand inhibitors (INSTIs) may have an effect on blood levels of some hormonal contraceptive agents. There are no known drug-drug interactions between ethinyl estradiol and nucleoside reverse transcriptase inhibitors (NRTIs), CCR5 antagonists, fusion inhibitors, or non-boosted INSTIs. Interactions vary between an decrease or increase in blood levels of ethinyl estradiol, norethindrone, or norgestimate. Such interactions could potentially result in decreased hormonal efficacy or increase hormonal adverse effects.
Transgender women may prioritize hormone therapy over other care; such symptoms may result in decreased ART adherence if it is perceived that these symptoms are due to ART. Consider monitoring estradiol levels and/or making empiric dosing or regimen adjustments based on development of or changes in estrogenic symptoms when initiating or changing anti-retroviral therapy.
There are limited data on the interactions between ART and masculinizing hormones or other drugs used as anti-androgens for feminization. Currently, there are no documented interactions between ART and either androgens (e.g., testosterone) or anti-androgens (e.g., spironolactone).
Hormone therapy and management of HIV-related opportunistic infections and prophylaxis
Patients with immunosuppression due to HIV may require treatment or prophylaxis for opportunistic infections. Most commonly this involves Trimethoprim - Sulfamethoxazole (TMP-SMX) daily for prevention of PCP pneumonia. A significant interaction leading to hyperkalemia, hospitalizations and deaths has been described in non-transgender patients between spironolactone and TMP-SMX. It is advisable to maintain a high index of suspicion when these drugs are used in combination, with frequent monitoring of serum electrolytes and renal function. Avoiding this combination is especially recommended especially in older patients.[15,16]
- Sevelius JM, Keatley J, Gutierrez-Mock L. HIV/AIDS programming in the United States: considerations affecting transgender women and girls. Womens Health Issues Off Publ Jacobs Inst Womens Health. 2011 Nov;21(6 Suppl):S278-82.
- Meier SC, Pardo ST, Labuski C, Babcock J. Measures of clinical health among female-to-male transgender persons as a function of sexual orientation. Arch Sex Behav. 2013 Apr;42(3):463-74.
- Light AD, Obedin-Maliver J, Sevelius JM, Kerns JL. Transgender men who experienced pregnancy after female-to-male gender transitioning. Obstet Gynecol. 2014 Dec;124(6):1120-7.
- 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. 2015 Sep 18;
- Poteat T, Wirtz AL, Radix A, Borquez A, Silva-Santisteban A, Deutsch MB, et al. HIV risk and preventive interventions in transgender women sex workers. Lancet. 2015 Jan 17;385(9964):274-86.
- Preexposure prophylaxis for the prevention of HIV in the United States - 2014: A clinical practice guideline. Centers for Disease Control and Prevention, U.S. Public Health Service.
- Deutsch MB, Glidden DV, Sevelius J, Keatley J, McMahan V, Guanira J, et al. HIV pre-exposure prophylaxis in transgender women: a subgroup analysis of the iPrEx trial. Lancet HIV . 2015 Nov [cited 2015 Nov 12];
- Sevelius JM, Keatley J, Calma N, Arnold E. "I am not a man": Trans-specific barriers and facilitators to PrEP acceptability among transgender women. In Florida; 2015.
- 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 Publ Soc Behav Med. 2014 Feb;47(1):5-16.
- Sevelius JM, Carrico A, Johnson MO. Antiretroviral therapy adherence among transgender women living with HIV. J Assoc Nurses AIDS Care JANAC. 2010 Jun;21(3):256-64.
- Sevelius JM, Saberi P, Johnson MO. Correlates of antiretroviral adherence and viral load among transgender women living with HIV. AIDS Care. 2014;26(8):976-82.
- World Health Organization WHO. Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations. WHO.[cited 2016 Jan 29].
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. [cited 2016 Jan 29].
- Panel on Antiretroviral Guidelines for Adults and Adolescents. World Health Organization (WHO) Guidelines: HIV. WHO. [cited 2014 Dec 3].
- Antoniou T, Gomes T, Mamdani MM, Yao Z, Hellings C, Garg AX, et al. Trimethoprim-sulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case-control study. BMJ. 2011;343:d5228.
- Antoniou T, Hollands S, Macdonald EM, Gomes T, Mamdani MM, Juurlink DN, et al. Trimethoprim-sulfamethoxazole and risk of sudden death among patients taking spironolactone. CMAJ Can Med Assoc J J Assoc Medicale Can. 2015 Mar 3;187(4):E138-43.