Women currently represent half of all
people who live with HIV globally, and that proportion is increasing in some
world regions. Yet women are considerably under-represented in HIV clinical
trials: since 2000, only 20% of participants in clinical trials of
antiretroviral therapy (ART) were women and the proportion has declined in the
past 8 years.1
This leaves a significant gap in
understanding of women and HIV, which is discussed in a recently published
opinion piece by Women for Positive Action.2
The risk to the foetus
of maternal medication in pregnancy, exemplified by thalidomide in the 1950s
and 1960s, has dominated discussions about the enrolment of women into clinical
trials. In the United States,
the Food and Drug Administration forbade women from participating during the
early stages of pregnancy following this tragedy. The repercussions meant that
many women were precluded from clinical trials.
More recently, the
need to include more women in clinical trials has been given greater attention
in order to have sample sizes large enough to take participant’s sex into
account. However, it is clear that the balance has not yet been achieved.
female representation in clinical trials over the past ten years is significant
not only because half of all people living with HIV are female, but also
because women may respond differently to both the disease and ART than men do.
For example, women have been consistently shown to have lower viral loads than
men at similar stages of HIV infection, most markedly early on, following HIV
seroconversion.3 However, the cause and significance of viral load
differences remain unclear.
addition, it has been suggested that women may respond better to ART than men:
in one study, women had better CD4-count responses to therapy and lower death
rates, though they experienced more drug-related side-effects.4 However,
existing studies don't provide a clear picture about the use of ART among
physical make-up is different to men’s: they have a lower
body mass, higher body-fat content and hormonal differences. Adverse effects and the ability to tolerate
certain antiretroviral drugs may differ in women. Birth control pills, hormone
replacement therapy and pregnancy could also alter the effects of HIV medications.
Without data investigating the impact of these on treatment in women with HIV,
potential improvements to the lives of millions of women are impeded.
clinical trials have been successful in increasing women’s participation. For
example, 38% of participants in the STEP trial, which aimed to find a
preventive HIV vaccine, were women.
GRACE Study5 was specifically designed to assess sex-based
differences in the efficacy and safety of darunavir boosted with ritonavir
(DRV/r), To achieve the recruitment goal of 420 patients (approximately 70%
female), each study site was required to enrol three women before enrolling a
man. Of the 429 people living with HIV enrolled, 287 were women.
Women living with HIV must also understand the importance of them volunteering to participate in clinical trials.
What we learn from women today can be applied to women's care in the future.
Professor Margaret Johnson, Royal Free Hospital, London
reported similar treatment response rates between men and women, but over a
third of women dropped out of the trial compared with under a quarter of men;
some discontinuations may represent challenges unique to women in clinical
trials. For future studies, the authors highlighted the importance of
addressing the unique needs of women during the screening process and
throughout, to optimise study retention
According to the founder and Chair of The
Well Project, Dawn
“GRACE sets a new standard for how future HIV studies should be conducted, as
we now know that treatment-experienced women…can and will successfully
participate in clinical trials if the studies are designed and supported in the
Given these recent successes, how can we continue to ensure
that more women are included in HIV clinical trials? Researchers, physicians
and clinical trial sponsors all need to take action in order to address the imbalance.
Professor Jane Anderson, HIV consultant physician
at Homerton University Hospital, London, elaborates: “The under-representation of women in HIV-related clinical trials falls
into three main areas: the study design and protocol, increasing the
participation of women in trials and raising awareness across the HIV field
that more studies and data analysis is needed in women.”
Clinical researchers need to ensure equal sex representation
in the early stages of drug development. At the same time, clinical trials should
be designed to give meaningful data on sex-related differences and remove
unfair barriers to female participation. For example, the provision of
childcare and other social support can often be seen as unaffordable or unnecessary, but these can be critical
to women’s participation.
women in the planning stages of clinical trials will allow these issues to be
raised. Furthermore, physicians should work
closely with investigators to support the inclusion of women, and clinical
trial sponsors should find ways to collaborate with centres and investigators
that treat a high proportion of HIV-positive women.
“More women should
be involved in the planning and implementation of studies to ensure the needs of
female participants are considered,” notes Professor Margaret Johnson, consultant
physician at London’s Royal Free Hospital. “Women living with HIV must
also understand the importance of them volunteering to participate in clinical
trials. What we learn from women today can be applied to women’s care in the
researchers and doctors, the national and supranational regulatory authorities can
have a positive effect on women’s representation in clinical trials. Journals
that publish HIV research and conference organisers also play significant roles
in drawing attention to the importance of the issue: editors and organisers
should encourage submissions focusing on women and include female health
specialists on editorial and conference boards.
Improving women’s health is not only a women’s issue. As
the GRACE study in the United States proved, by learning more about how women
respond to HIV treatments and by improving their total quality of care, we can not
only improve their quality of life but also that of their partners, children
Ssanyu-Sseruma of Christian Aid believes that “Encouraging the participation of community representatives in the
planning and implementation of trials is vital. Community involvement at all
levels is essential if we are to enrol more women in clinical trials.”
in medicine, research, public health and communities can improve the lives of
women living with HIV, but specific data on the effects of treatments will be
essential. Together, we need to ensure that women around the world can benefit
from the knowledge gained through HIV clinical trials.