Trial Finds Women Respond as Well as Men to HIV Treatment, but More
Likely to Stop Therapy
HIV positive women and men taking antiretroviral therapy
(ART) containing boosted darunavir (Prezista) had statistically
similar treatment response rates, with the slightly
poorer outcomes among women probably due to their higher
likelihood of discontinuing therapy, according to a
report of findings from the GRACE (Gender, Race And
Clinical Experience) study published in the September
21, 2010 Annals of Internal Medicine. GRACE
showed that it is possible to recruit and conduct a
clinical trial with a large number of women, many of
them socioeconomically disadvantaged, but the 33% dropout
rate suggests additional efforts are needed to retain
women in such studies.
is an excerpt from a press release issued by Tibotec, which produces
darunavir, describing the GRACE study and its findings.
from Landmark Study Evaluating Gender Differences in Response
to an HIV Therapy Published in Annals of Internal Medicine
GRACE study has significant implications for inclusion of
women in clinical trials
NJ -- September 20, 2010 -- Data from the GRACE (Gender,
Race And Clinical Experience) study will be published in
the September 21st issue of the Annals of Internal Medicine.
GRACE is the largest-ever study of treatment-experienced
adult women with HIV-1 to examine gender differences in
response to HIV therapy. Sponsored by Tibotec Therapeutics
Clinical Affairs, a division of Centocor Ortho Biotech Services,
LLC, the GRACE study enrolled 67 percent women, demonstrating
that it is possible to recruit large numbers of women into
U.S.-based HIV treatment studies. The company has launched
to share learnings from the GRACE study and other information
for women living with HIV.
Among patients who completed the study, there were no significant
differences in treatment responses between men and women
who were given Prezista (darunavir) 600 mg coadministered
with 100 mg ritonavir twice daily, as part of combination
therapy. The GRACE study was designed in partnership with
the HIV community and used unique strategies to encourage
women living with HIV to participate in the trial. However,
even with its novel enrollment strategies, the study showed
a higher discontinuation rate among female study participants
-- making the overall response rate lower among women than
among men, and shedding light on the need for additional
efforts to retain diverse populations in clinical studies.
"Better representation of women in clinical trials
is essential for generating accurate information on the
efficacy and safety of medicines and, ultimately, guiding
treatment decisions," said Judith Currier, MD, Professor
of Medicine, Associate Division Chief, Division of Infectious
Diseases, University of California, Los Angeles, Director
of the Clinical Trials Unit, UCLA Center for Clinical AIDS
Research and Education (CARE), and primary investigator
in the GRACE study. "The GRACE study has the potential
to shape how future studies are conducted because it addressed
the social and economic barriers that historically have
prevented women from participating in clinical research.
It also showed that we have a long way to go before we can
fully overcome these barriers."
In the United States, women account for an increasing proportion
of people living with HIV/AIDS, including more than one
quarter of new diagnoses. Yet despite their growing numbers,
women have been under-represented in HIV treatment studies.
This may be due to recruitment and retention challenges
including family commitments, time constraints with jobs,
and other socioeconomic factors. These observations have
been noted in clinical trials of other therapeutic areas,
including heart disease and cancer, suggesting that difficulties
in recruiting women are not specific to HIV clinical trials.
As a result of having a low number of women in these studies,
gender-based conclusions are limited, and there remains
a gap in clinical data.
"Unlike most studies of HIV medicines, GRACE was specifically
designed and powered to assess gender differences in response
to treatment," said Dr. Currier. "We took steps
that have never before been used to make sure our study
population was reflective of the demographics of women with
HIV in the United States."
GRACE Study Design and Results
GRACE was a multi-center (65 sites), open-label Phase 3b
trial that compared the efficacy, safety, and tolerability
of the protease inhibitor Prezista (600 mg) boosted with
a low dose of ritonavir (100 mg) twice a day, in combination
with an investigator-selected optimized background regimen
for 48 weeks in men (n=142) and women (n=287).
The study was designed to enroll a high proportion of North
American, treatment-experienced women that was reflective
of the distribution and demographics of women with HIV in
the United States. Trial sites were selected to correspond
with the geographic distribution of women with HIV, with
the majority of sites located in the Northeastern (16 sites)
and Southeastern (29 sites) United States. Study sites were
initially required to enroll three women before enrolling
a man, and thereafter, each site was required to maintain
at least 70 percent female enrollment. Men could only be
enrolled if their addition did not compromise the 70 percent
GRACE participants also received support to cover costs
associated with study participation, including assistance
for travel, childcare and food vouchers, and study sites
could access grants for patient support activities such
as lunch-and-learn sessions and patient support groups for
ongoing education and camaraderie.
At the end of the study period, there were no statistically
significant differences in virologic response (defined as
a viral load of < 50 copies/mL) rates between women and
men. Results from an intent-to-treat time-to-loss of virological
response analysis (ITT-TLOVR) showed that 50.9 percent of
women reached an undetectable viral load (< 50 copies/mL)
at week 48 compared with 58.5 percent of men (p=not significant).
These figures included men and women who had discontinued
the study. When treatment discontinuations for reasons other
than virologic failure were discounted, 73 percent of women
and 73.5 percent of men reached an undetectable viral load
Discontinuation rates driven by reasons other than virologic
failure were 32.8 percent for women versus 23.2 percent
for men. Loss to follow-up was the most common reason for
discontinuation. There were no clinically relevant differences
in safety or tolerability between women and men. In adult
patients receiving a Prezista/ritonavir-containing regimen,
the most common treatment-related adverse events (? 2 percent)
reported of at least moderate to severe intensity (>
Grade 2) were nausea (5.2 percent for women and 2.8 percent
for men), diarrhea (4.5 percent for women and 4.9 percent
for men) and rash (2.1 percent for women and 2.8 percent
Additional analyses were conducted as part of the GRACE
study, including a sub-study examining efficacy and safety
differences in response to race, as well as an immunology
Full prescribing information for darunavir is available
About Tibotec Therapeutics
Tibotec Therapeutics, a division of Centocor Ortho Biotech
Products, LP, headquartered in Titusville, NJ, is dedicated
to delivering innovative virology therapeutics that help
healthcare professionals address serious unmet needs in
people living with HIV. For more information, visit www.Tibotec.com.
affiliations: University of California, Los Angeles, School of
Medicine, Los Angeles, CA; The Well Project, Nellysford, VA; Chatham
County Health Department, Savannah, GA; University of Puerto Rico
School of Medicine, San Juan, PR; University of Cincinnati College
of Medicine, Cincinnati, OH; Tibotec and Tibotec Therapeutics,
Titusville, NJ: Jefferson Medical College of Thomas Jefferson
University, Philadelphia, PA.
J Currier, D Averitt Bridge, D Hagins, and others (GRACE Study
Group). Sex-Based Outcomes of Darunavir-Ritonavir Therapy: A Single-Group
Trial. Annals of Internal Medicine 153(6): 349-357 (Abstract).
September 21, 2010.
Data from Landmark Study Evaluating Gender Differences in Response
to an HIV Therapy Published in Annals of Internal Medicine.
Press release. September 20, 2010.
of Success in HIV: Proven Interventions for Improving
wareness, Testing, Access to Care, and Treatment of HIV in
Communities of Color.
of Success in HIV: Proven
Interventions for Improving wareness, Testing, Access to Care,
and Treatment of HIV in Communities of Color.