By: Dr. Shelly Karuna- HVTN, Seattle, WA, USA, with contributions from the HVTN 505 Protocol Team
The phase 2b HVTN 505 study (n=2,504) opened in May 2008 and the final participant enrolled in March 2013. The trial assessed the safety and efficacy of a preventive DNA/rAd5 HIV vaccine regimen in MSM and transgender women (TGW) who have sex with men who were at risk for acquiring HIV. It was HVTN’s first trial to specifically include TGW, distinct from MSM. Though by eligibility criteria participants were required to have been assigned male sex at birth, no required gender identity was specified and 44 participants did not identify as having a male gender identity at study entry. These 44 identified their gender as: transgender female (n=28); female (8); transgender male (2); queer (2), gender queer (1); born male with female hormones (1); not claiming male or female, no sex (1); or decline to state (1). These 44 individuals were included as “transgender” (ie, their sex assigned at birth was discordant from their gender identity) in a comparative analysis of HVTN 505 transgender and cisgender participants. This analysis compared transgender and cisgender participants in HVTN 505. Eight participants were excluded who were found to have been HIV-infected upon enrollment, for a total of 2,496 HVTN 505 participants included in this comparative analysis.
ϕSome of these conditions are referable to participants’ TG status (eg, gender dysphoria)
HVTN 505 transgender (TG) participants were more likely than cisgender (CG) participants to have demographic factors associated with HIV incidence[GBB1] , including non-White race (57% TG vs. 24% CG; p<.001) and young age (average 29 vs. 32 years old; p=0.04). Of the TG ppts, 14% identified as Hispanic, 43% White, 41% African-American, 11% “other,” and 2% each as Asian or multi-racial. [Editor’s note: a statistic is defined as “significant” when the p value is <.05.]
More transgender participants than cisgender participants missed at least one study visit (34% vs. 21%; p=.01). There was no statistically significant difference in other retention factors such as stopping vaccinations or dropping out of the study. Trans and cis participants did not differ in average number of pre-existing conditions or adverse events (AEs), including serious AEs. There were more deaths among TG ppts (n=2 or 5% vs. n=7 or 0.29%; p=.01).
Transgender participants said that “a friend joined” as a reason to enroll more often than cisgender participants, which may prove informative for future transgender engagement & recruitment. Both trans and cis individuals reported participating primarily for altruistic reasons.
There were no differences in numbers of social harms or benefits. 87% of participants reported experiencing social benefits to trial participation. The most common benefit was feeling good about helping others, reported by 75% of TG and 70% of CG participants. Other benefits included: receiving risk reduction counseling (50% TG, 42% CG); receiving medical care (46% TG, 29% CG); and positive impacts on personal relationships (36% TG, 31% CG).
New HIV infections were higher among TG ppts. However, the difference was not statistically significant, although there was limited power to detect a difference because of the small number of transgender participants who were included (3 TG ppts or 4.3/100 person-yrs vs. 84 CG ppts or 2.1/100 p-y; p=0.37).
In conclusion, transgender and cisgender participants at risk of HIV can be successfully recruited and retained, and contribute meaningfully to HIV vaccine clinical trials.
In March 2011 the Institute of Medicine (IOM) published a report of lesbian, gay, bisexual, and transgender health in which it was noted that transgender individuals (TG) in the US have increased risks of adverse health outcomes, generally. With respect to HIV infection, specifically, prevalence and incidence rates are much higher among TG than among cisgender (CG) individuals, with prevalence among black TG approaching 25%. This is largely attributed to complex relationships between known predictors of HIV incidence such as sero-discordant primary partners, unprotected anal intercourse, sex work and drug use, as well as the interaction of interpersonal, social, and structural variables with these predictors.
TG are, thus, among those most in need of an HIV vaccine. Yet, TG experience increased rates of stigma, discrimination, and prejudice and these factors—alongside lower educational attainment and income, employment discrimination risks, and reduced social support—create significant barriers to HIV vaccine trial participation.
Dr. Shelly Karuna is the Director of Clinical Development for the HVTN and the Protocol Team Leader for HVTN 505.