Absence
of Sex Differences in Fosamprenavir Efficacy and Safety
Sex-related
differences in toxicity and response to many antiretroviral agents have not been
well studied and deserve further evaluation.
Researchers
with GlaxoSmithKline and the University of California at Los Angeles systematically
analyzed sex differences in efficacy and toxicity in 3 pivotal trials of the protease
inhibitor (PI) fosamprenavir (Lexiva), administered with and without ritonavir
(Norvir). Results were reported at the 46th Interscience Conference on Antimicrobial
Agents and Chemotherapy, taking place this week in San Francisco.
Rates
of treatment discontinuation, grade 2-4 adverse events, and therapeutic efficacy
were compared within 2 studies of treatment-naive participants (NEAT and SOLO)
and 1 study of PI-experienced patients (CONTEXT).
The
demographics of the study populations are shown in the chart below:
Enrollment of treatment-naive women into the pivotal trials of fosamprenavir exceeded
25%.
There were no apparent sex differences in response to treatment, defined as viral
load below 400 copies/mL at Weeks 24 and 48.
Rates of premature treatment discontinuation did not vary by sex in the NEAT or
SOLO trials.
In the CONTEXT trial, however, women discontinued at a rate twice that seen in
men in the fosamprenavir/ritonavir once-daily arm, but at half the rate in the
fosamprenavir/ritonavir twice-daily arm.
Women were more likely to report upper respiratory tract infections and headache,
while men reported higher rates of diarrhea.
Men were more likely to have elevations in transaminases (liver enzymes), triglycerides,
and cholesterol compared with women.
Rates of premature discontinuation and adverse events are shown in the chart below:
Outcome
NEAT 908 QD
SOLO 908/r QD
CONTEXT 908/r QD
CONTEXT 908 BID
Men
Women
Men
Women
Men
Women
Men
Women
Premature
d/c of PI
30%
29%
27%
30%
22%
47%
28%
14%
Grade 2-4
AE
69%
64%
75%
77%
71%
76%
71%
93%
d/c
= discontinuation; AE = adverse event
Conclusion
According
to the researchers, "Fosamprenavir was effective and well tolerated among
women and men. Overall, no sex differences in efficacy or toxicity were identified."
Univ.
of California, Los Angeles, CA; Glaxo SmithKline, Research Triangle Park, NC;
Glaxo SmithKline, Greenford, U.K.
09/29/06
Reference J
S Currier, O Umeh, C Garris, N Givens. Absence of Sex Differences in Fosamprenavir
Efficacy and Safety: Results of a Systematic Review of Pivotal Trials. 46th Interscience
Conference on Antimicrobial Agents and Chemotherapy. San Francisco, CA. September
27-30, 2006. Abstract H-1400.
Researchers
with GlaxoSmithKline and the University of California at Los Angeles systematically
analyzed sex differences in efficacy and toxicity in 3 pivotal trials of the 
Enrollment of treatment-naive women into the pivotal trials of fosamprenavir exceeded
25%. 