How can we improve uptake of oral HIV pre-exposure prophylaxis for transgender individuals?

KEYWORDS:

• Pre-exposure prophylaxis
• transgender
• HIV
• biomedical intervention
• gender-affirmation

1. Introduction

Transgender people, i.e., those whose gender identity differs from the sex they were assigned at birth, have been shown to be disproportionately affected by HIV. Transgender women have an estimated global HIV prevalence of 19.1%, a rate consistently higher than almost any other key population [1]. In the USA, the vast majority of transgender individuals affected are people of color with a reported HIV prevalence among African-American transgender women of 44.1% [2]. Over half of all new HIV diagnoses in transgender people occur in African-Americans [3]. Few data exist for HIV prevalence among transgender men, however studies frequently report increased HIV risk behaviors, including condomless anal sex and sexually transmitted infections [2,4–7] in this population. The recent estimate of 3.2% in transgender men far exceeds the US general population prevalence [2]. The elevated HIV prevalence in transgender populations is due to a combination of psychosocial and structural factors, such as high rates of societal stigma and discrimination leading to unemployment, poverty, psychological stress, mood disorders, and reduced access to health care including HIV prevention interventions [8].

2. PrEP and transgender people

The World Health Organization recommends the use of oral HIV Pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate/(F/TDF) for populations at substantial risk, defined as HIV incidence greater than 3 per 100 person–years [9]. Several studies have confirmed that HIV incidence among transgender women often exceeds this cutoff [10–13] establishing this as a priority population for PrEP implementation. However, evidence suggests that uptake of PrEP remains suboptimal, especially among transgender women of color and transgender youth [14–18]. Several studies reveal low rates of knowledge about PrEP among transgender women, both in the USA and internationally [19,20], although when informed about PrEP, interest and willingness to use it is high [14,21–23]. Similar trends are seen among transgender men with low rates of PrEP uptake despite clear indications for its use [24,25].

The only published study on oral PrEP efficacy that included substantial numbers of transgender women was the iPrEx trial [26]. A secondary analysis revealed that oral PrEP was not efficacious in transgender women [27]; however, this may have been due to extremely low rates of adherence of participants to the study drug. In addition, differences in baseline characteristics between the cisgender (i.e., not transgender) men who have sex with men (MSM) and transgender women participants may have explained the observed effect heterogeneity [28]. When used, PrEP appears to be effective in transgender women. Drug concentrations in iPrEx strongly correlated with PrEP protection, with no HIV infections occurring in transgender women who had drug concentrations equivalence to four or more tablets per week [12,29].

Pharmacokinetic studies to evaluate possible drug–drug interactions between feminizing therapy and antiretrovirals have indicated that plasma levels of tenofovir may be lower in the presence of estradiol however the clinical significance of this finding is not known. In both studies, the estradiol levels were not affected by the presence of oral PrEP [30,31].

3. Why are transgender people not taking PrEP?

There are many reasons for low uptake of PrEP in transgender communities, including lack of knowledge [19,21,32–34], concerns about side effects [21,23,35–38] or drug interactions with hormone therapy (both estrogens and testosterone) [14,22,33,37,38], inability to find trans competent providers [33,35], providers not discussing or offering PrEP [25,37], financial/insurance issues [21,23,33,37,39], avoidance of healthcare due to discrimination or medical mistrust [21,22,32,40], low risk perception [23,34,41], fear of being HIV positive [23,32], adherence concerns or difficulty taking pills [21,32,36], HIV and PrEP stigma [23,36,38,42], and not being included in prevention campaigns [22,36]. Transgender youth may experience more additional barriers due to being legal minors as well as fear of parental disclosure [41,43].

An important entry point to PrEP is HIV testing. In the USA there is evidence that transgender people, despite having elevated risk for HIV, have a significantly lower prevalence of ever testing and past year testing for HIV compared with cisgender MSM [44].

4. How can we improve uptake of PrEP in transgender populations?

There is a desperate need to improve PrEP utilization in transgender populations, especially among youth and transgender people of color. The barriers to PrEP offer some enlightenment. Firstly, we must start with improving education about PrEP to address knowledge gaps in transgender communities. Strategies that have been employed include implementing social marketing campaigns and tools designed specifically targeted toward transgender communities. These campaigns have the added benefits of stigma reduction and improved uptake of PrEP [45,46]. PrEP peer navigation programs have also been helpful in disseminating information about PrEP and successfully improving linkage to PrEP and optimizing adherence [47].

PrEP care is often embedded in health systems that are not welcoming to transgender and gender diverse people, so improving healthcare accessibility, with a focus on building cultural humility among health-care workers and creating welcoming settings needs to be prioritized. Providers need to be competent to discuss issues of sexuality, sexual, and reproductive health of transgender people [33]. Other options for PrEP delivery include creating community and health-care partnerships, whereby transgender people can access health services in settings they feel most comfortable, such as community-based organizations or mobile health services [40,48].

Access to gender-affirming hormones is a strong motivator for engagement in medical services, including PrEP utilization [16,49]. Scaling up knowledge among medical providers and other health-care workers about transgender medicine protocols and providing hormone care to patients is a mainstay of welcoming and gender-affirming care services. Health-care workers in clinics and other health settings that want to improve PrEP delivery to transgender people should understand the full context of their lives, and facilitate access (either directly or by referral) to housing, legal aid, food services, and educational support when needed. Financial barriers can be mitigated through linkage to low cost or free medication and insurance navigation. Patients may also benefit further from access to comprehensive PrEP programs that include peer-based empowerment and support [50].

As part of care, clients need to have information based on available studies that PrEP does not adversely affect the levels of gender-affirming hormones [30,31], since this fear of drug interactions has been shown to impede PrEP uptake.

It is imperative that transgender people are integral to the conversation about PrEP scale-up in their communities. So far, few studies of PrEP implementation have taken into account the contributions of transgender people. In one evaluation that included transgender participants, key components to increase PrEP use also underscored the importance of not conflating transgender and nonbinary individuals with cisgender men who have sex with men and active provider engagement and community mobilization [51].

Looking to the future, there is a need to improve the number and quality of research studies that include transgender people in meaningful numbers as they have been traditionally underrepresented in prevention research [33,36,52,53]. Even more important is the development of interventions that are specifically designed for transgender people. The recent FDA approval of a second agent for oral PrEP, emtricitabine, and tenofovir alafenamide (F/TAF) relied on trial data that included few transgender people (1%), and there is no information on inclusion of transgender people in the new pipeline studies evaluating other new agents such as long-acting injectables, e.g., cabotegravir, broadly neutralizing monoclonal antibodies and other novel technologies [54]. These new modalities of PrEP may help to address some of the access and adherence challenges experienced by transgender communities but must first be investigated for efficacy, feasibility, and acceptability.

Transgender people have been shown to have a disproportionate risk for HIV however use of PrEP is underutilized in this population. As PrEP implementation increases across the US, it is important to ensure that transgender people are not left behind. HIV prevention programs that aim to be transgender-inclusive will need to address the barriers frequently faced by transgender communities. Priorities for these programs should include scaling up of HIV-testing, addressing knowledge gaps about PrEP among clients, access to culturally competent and knowledgeable providers and integrating or facilitating access to gender-affirming medical services, such as hormone therapy.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.