The more than 300 transgender women in the pivotal iPrEx pre-exposure prophylaxis (PrEP) trial had similar
overall HIV infection rates whether they were randomised to take Truvada or placebo, but those with drug
levels indicating consistent PrEP use appeared to be protected, researchers
reported in the November 5 advance online edition
of The Lancet.
this analysis did not include a large enough sample group to draw firm
conclusions, we did find strong evidence pointing to efficacy," said
senior study author Robert Grant of the University of California at San Francisco. "Additional research designed specifically for
transgender women is needed to confirm this finding."
US Food and Drug Administration approval of Truvada (tenofovir/emtricitabine) for
PrEP in July 2012 was based in part on data from the phase 3 iPrEx
trial, which enrolled 2,499 mostly gay and bisexual men
from Brazil, Ecuador, Peru, South Africa,
Thailand and the US between 2007 and 2009. Participants were randomly
assigned to take oral Truvada or a
placebo once-daily. Follow-up in the randomised portion of the study continued
for a median of 1.2 years. Afterwards participants had the option to receive Truvada in an open-label extension of
the study, which ended in 2013.
Primary results, published in
November 2010, showed that once-daily Truvada reduced the risk of HIV infection by 42% overall compared
to placebo, rising to 73% among participants who reported good adherence and
92% among those with blood drug level measurements indicating regular use. In the open-label extension no one
who took Truvada at least four times a week became infected.
Transgender women have one of the highest rates of HIV
infection. One meta-analysis of 22 studies
found that 28% of transgender women in the US are HIV-positive, while a 2013
meta-analysis looking at 15 countries found that 19% of trans women were living
with HIV, the researchers noted as background.
To date, no randomised
clinical trials have looked specifically at PrEP for transgender women, and it
is not known whether hormone use or other factors might affect its safety and
effectiveness for this group. This is the first separate analysis of trans
women in a Truvada PrEP trial.
Dr Grant, Madeline Deutsch and fellow
investigators performed an unplanned analysis of PrEP efficacy, overall
effectiveness and adherence among trans women in iPrEx, comparing PrEP outcomes
between trans women and men who have sex with men (MSM).
While most of the 2,499 iPrEx participants were
gay and bi men, a total of 339 (14%) were classified as transgender women,
including 29 (1%) who identified as women, 296 (12%) who identified as trans or
'travesti', and 14 (1%) who identified as men but reported use of feminising
hormones. Of these 192 joined the open-label extension, 79% of whom opted to
The initial published iPrEx report said the
study included 29 trans women, but a "more sophisticated method" for
determining who was transgender turned up a larger number, Grant said in a UCSF press release.
In the US just 3% of participants were classified as
transgender women, rising to 6% in South Africa, 10% in Brazil, 15% in Ecuador
and Peru, and 38% in Thailand. The median age of trans women was 26 years (a
year younger than the MSM). Only 4% were circumcised, which has been linked to
increased HIV risk in some populations. One-fifth reported use of feminising
Compared with MSM, transgender women more
frequently reported sex work or transactional sex (64% vs 38%), condomless
receptive anal intercourse (86% vs 55%), sexually transmitted infections during
the past six months (38% vs 24%) and more than five sex partners during the
past three months.
In the randomised trial transgender women had lower drug levels in their blood and were less
likely to take PrEP on a daily basis than MSM. PrEP use was not linked
to behavioural risk among trans women – and in fact those who reported
condomless anal sex tended to be less likely to use PrEP consistently – unlike
MSM, for whom those at highest risk had better adherence.
Among transgender women, 11 new HIV infections
occurred in the PrEP group and 10 in the placebo group during the randomised
study – essentially no difference (hazard ratio 1.1). Two transgender women
receiving PrEP seroconverted in the open-label extension.
None of the 11 trans women who seroconverted in
the randomised trial had detectable blood drug levels. In the open-label
extension transgender women were half as likely as MSM to have drug levels
indicating they took four or more doses of Truvada
a week (18% vs 36% of follow-up time, respectively). Trans women who took
feminising hormones were less likely to have detectable drug levels or
protective drug levels.
However, none of the trans women with drug
levels indicating they took at least four doses a week became infected, as was
the case for MSM. HIV incidence among trans women was 0 if drug was detected
and 4.9 per 100 person-years if drug was not detected, compared with 0.4 and
2.8 per 100 person-years, respectively, among MSM.
Truvada PrEP was
generally well-tolerated. Moderate or severe adverse events were rare among
transgender women, with no differences between the PrEP and placebo groups. Bone
mineral density tended to be less affected by PrEP among trans women than among
MSM, which the researchers suggested might reflect less actual use of PrEP or a
protective effect of feminising hormones. There was no evidence of liver
"PrEP seems to be effective in preventing
HIV acquisition in transgender women when taken, but there seem to be barriers
to adherence, particularly among those at the most risk," the study
authors concluded. "Studies of PrEP use in transgender women populations
should be designed and tailored specifically for this population, rather than
adapted from or subsumed into studies of MSM."
face several structural barriers including lack of legal protection against
discrimination and resulting difficulties in employment, access to income, food
and housing, Deutsch said in the UCSF press release. "They
desperately need a tool that they control, one they can use without their
partners' consent or knowledge."
"We think that one
factor leading to lower rates of pill-taking may be due to either a fear of, or
lack of information about drug-drug interactions between PrEP and
gender-affirming hormone medications. For transgender women, their
gender-affirming medications are a higher priority," she continued.
"And while there may be a negative behavioural interaction between the two
therapies that is affecting pill-taking, we have no evidence to date for a
biological interaction between the two, though further research is
women take PrEP as prescribed, it appears to work, but to retain and encourage
PrEP use, research should be conducted and interventions should be delivered in
gender-affirming environments," said co-author JoAnne Keatley, director of the UCSF Center of Excellence for Transgender Health. "One example would be to integrate
PrEP delivery with gender-affirming services, including provision of
gender-affirming hormone therapies. Social marketing campaigns and PrEP
delivery programs should not lump transgender women in with MSM, but should be
explicitly designed to support transgender women."