Transgender communities are among the groups at highest risk for HIV and other STD infections. It has been estimated that HIV prevalence for transgender women is nearly 50 times as high as for other adults of reproductive age [5]. The average prevalence in this population is about 27.7 %.

Reliable information on how many transgender people are infected with HIV is lacking because it is very difficult to collect data uniformly. Gender expression may fluctuate for some transgender people, and there is great diversity in orientation and behavior in this population. In addition some transgender people may not identify as transgender due to fear of discrimination or previous negative experiences [6].

Data collected by local health departments and scientists studying these communities in the United States show high levels of HIV infection and racial disparities. In 2010, the Centers for Disease Control and Prevention (CDC) reported that the highest percentage of newly identified HIV-positive test results was among transgender people. Among transgender people, the highest percentages of newly identified HIV-positive test results were among ethnic minorities above all African Americans, followed by Latinos. Most studies confirm that black transgender women are more likely to become infected with HIV than nonblack transgender women [7]. Over half of newly diagnosed transgender women were in their twenties. Also, among newly diagnosed, it is very likely to report documentation in medical records of substance use, commercial sex work, homelessness, incarceration, and sexual abuse as compared with other people who were not transgender [8, 9].

Although there remains globally a poor understanding of the burden of HIV among transgender women, it is evident that they are a higher-risk population and in urgent need of prevention, treatment, and care services [10].

Transgender men’s sexual health has been understudied. Compared to transgender women, little is known about HIV risk and sexual health needs among transgender men. This is because they have not traditionally been considered at risk for HIV due to different sexual exposure. Prevalence of HIV infection among female-to-male (FTM) is considerably lower than among male-to-female (MTF) transgender people [11].

The high burden of HIV infection among transgender people is not attributable only to individual behaviors such as unprotected sexual intercourse and promiscuity. Also many cultural, socioeconomic, and health-related factors contribute to the HIV epidemic spread in transgender communities. Behaviors and factors that contribute to high risk of HIV infection among transgender people include higher rates of drug and alcohol abuse, sex work, incarceration, homelessness, attempted suicide, unemployment, lack of familial support, violence, stigma and discrimination, limited health-care access, and negative health-care encounters. In addition to biological and network-level factors, the structural risks for HIV infection, such as social exclusion, economic marginalization, and unmet health-care needs, transcend the level of the individual and might also help explain why HIV rates are so high in transgender women compared with other adults [12].

Discrimination and social stigma can hinder access to education, employment, and housing opportunities. And this statement may help explain why transgender people who experience significant economic difficulties often pursue high-risk activities, including sex work, to meet their basic survival needs. In general, sex workers have been shown to experience risk for various adverse health conditions, including HIV and other sexually transmitted infections [13, 14].

Health-care provider insensitivity to transgender identity or sexuality can be a barrier for HIV-infected transgender people seeking health care. Although research shows a similar proportion of HIV-positive transgender women have health insurance coverage as compared with other infected people who are not transgender, HIV-infected transgender women are less likely to be on antiretroviral therapy. Indicator of this situation is unawareness of one’s serostatus. As a matter of fact, CDC has reported that most of the transgender women who were tested HIV positive were unaware of their status and potential unknowing transmitters of infection.

A primary driver of HIV infection in transgender women, similar to MSM, is the very high transmission probability of unprotected receptive anal intercourse [12, 15]. Since transgender women have been consistently identified as engaging in receptive anal sex with men, this biological vulnerability to HIV acquisition is undoubtedly an important factor in the high acquisition risk identified. Anal intercourse is a much more efficient mode of HIV transmission than penile-vaginal intercourse. However, there is still little research on HIV acquisition risks from neovaginal intercourse after vaginoplasty as well as from sex between transgender women and female partners. As a matter of fact, consistent condom use with appropriate lubricants is an essential prevention method for anyone engaging in anal sex.

Other individual-level risks for HIV include high rates of depression that may drive to drug abuse as well as risk of parenteral acquisition through illicit hormone and silicone injections [16, 17].

Additional research is needed to identify factors that prevent HIV in this population. Several behavioral HIV prevention interventions developed for transgender people have been reported in studies, such as encouraging frequent HIV testing for identifying transgender people with undiagnosed HIV infection and safe sex practices. Most have shown at least modest reductions in HIV risk behaviors among transgender women, such as fewer sex partners and/or unprotected anal sex acts. Behavioral HIV prevention interventions developed for other at-risk groups with similar behaviors have been adapted for use with transgender people; however, their effectiveness is still unknown.

In the absence of a vaccine, HIV prevention involves combinations of strategies including behavioral interventions, widespread condom use with appropriate lubricants, male circumcision, STD treatment, early initiation of antiretroviral therapy (ART) after infection, and preexposure and postexposure antiretroviral prophylaxis (Table 39.2) [18].

In a recent study, ART in combination with condom use and counseling was found to reduce HIV transmission by 96 % among 1,763 serodiscordant couples (97 % heterosexual) in which the HIV-infected partner had a CD4 count of 350–550 cells/mm³ [19]. The outstanding results of this study also showed that earlier ART can provide significant benefit even to HIV-infected individuals with reduction of clinical events including extrapulmonary tuberculosis and others. According to these results, the World Health Organization (WHO) and the US Department of Health and Human Services (DHHS) recommend immediate ART for people in HIV discordant relationships, irrespective of CD4 cell count [20, 21]. Earlier epidemiological studies as well as mathematical models support the theory that promoting treatment of HIV will decrease HIV incidence. However, the effectiveness of HIV treatment as prevention among other individuals (i.e., homosexuals, transgender, intravenous drug users, sex workers) and settings (i.e., resource-limited countries) is still debatable. Furthermore, the treatment as prevention strategy also seems to be undermined by lack of universal agreement about when to start ART, whether for individual health, to prevent HIV transmission, or for both benefits combined [18]. To address these and other concerns, several studies are being planned or ongoing to evaluate the effectiveness of ART as part of combined prevention strategies [22].

Administration of antiretroviral drugs to uninfected persons at high risk of infection to protect against HIV acquisition is known as preexposure prophylaxis (PrEP). Over the last 3 years, several trials have shown that PrEP (including oral and topical tenofovir-based compounds) can decrease the incidence of HIV infection in various high-risk patient populations. However, other studies were discontinued early because of lack of efficacy of such strategy due to suboptimal adherence or different risk behaviors among participants. Thus, other trials including oral tenofovir-emtricitabine and pericoitally administered tenofovir gel are ongoing [22]. The first study demonstrating that PrEP can protect against HIV acquisition in humans showed that the pericoital use of tenofovir vaginal gel was associated with 39 % decrease in the risk for HIV acquisition among at-risk South African women after 2.5 years compared with placebo [23]. Several months later, a study in 2,499 MSM or transgender women receiving daily oral emtricitabine-tenofovir reported a 44 % reduction in new HIV infection. In addition, the result in participants with detectable antiretroviral drug levels in plasma was a 92 % reduction. All subjects received risk-reduction counseling, condoms, HIV testing, and treatment of sexually transmitted diseases. Elevation of serum creatinine levels was more frequent in the tenofovir group than in the placebo group. However, the two groups had similar rates of serious adverse events. In summary, although more information is needed about possible side effects regarding bone mineral density and drug resistance, the findings of such trial showed that a dual oral antiretroviral regimen provided protection against the acquisition of HIV infection among MSM or transgender women [24]. More recently, two studies demonstrated that daily oral PrEP with tenofovir-emtricitabine, given also in the context of other prevention services, reduced the risk of HIV acquisition by the HIV-uninfected partner in serodiscordant, heterosexual couples. The first trial showed a 75 % reduction in new infections with daily oral tenofovir-emtricitabine, and 67 % with tenofovir, again with results in patients with detectable drug levels [25]. In the second trial, daily oral tenofovir-emtricitabine decreased HIV incidence by 62 % [26]. Both trials showed that the efficacy of preexposure prophylaxis depends largely on adherence to the medication, and rates of serious adverse events were similar across the study groups. However, the active study medications were associated with increased reports of gastrointestinal side effects and, in the latter trial [26], significant decline in bone mineral density as compared with placebo. After data of these studies were available, the US Food and Drug Administration (FDA) approved tenofovir-emtricitabine for PrEP for HIV-uninfected MSM, HIV-uninfected partners in serodiscordant couples, and other individuals at risk of acquiring HIV through sexual activity. The CDC published guidance for the prescription of daily oral tenofovir-emtricitabine as PrEP to at-risk males who have sex with men [27]. The CDC recommended that providers document negative HIV antibody test results immediately before starting PrEP, test for acute HIV infection if symptoms consistent with this syndrome are present, and undergo serial, regular HIV testing during PrEP use. Persons who acquire HIV infection should immediately discontinue PrEP use to reduce the risk of drug resistance. The CDC also advised screening for other STDs, including hepatitis B virus. In summary, daily ingestion of oral PrEP may result to be desirable when potential exposure to HIV is frequent (i.e., serodiscordant couples, MSM with multiple partners, sex workers). On the other hand, pericoital topical PrEP allows high local drug exposure with lower systemic drug levels, probably leading to a decreased likelihood of drug toxicity and increased adherence. However, topical PrEP will result to be difficult to use without partner knowledge [28]. A study assessed the acceptability of oral PrEP and rectal PrEP during unprotected receptive anal intercourse among MSM and transgender women in Peru. Among 532 individuals, high acceptance of either oral daily (96 %) or rectal (92 %) PrEP products were reported. If both products were efficacious and available, 29 % would prefer a pill, 57 % a rectal lubricant, and 14 % either products. Therefore, the development of an effective antiretroviral-based rectal gel is likely to have high acceptability among subjects practicing receptive anal sex because of rates of rectal lubricant use that are high in such populations. In conclusion, the findings of this study suggest that efficacious oral or rectally formulated HIV PrEP interventions would be highly acceptable among MSM and transgender women practicing receptive anal sex and with concomitant high-risk sexual behavior [29]. The efficacy of administering PrEP to the HIV-uninfected partner of a monogamous couple, whose HIV-infected partner is receiving ART, is actually unknown. Integrating these two strategies into current behavioral interventions could allow to reduce considerably the incidence of new HIV infections among serodiscordant couples.