Columbia Laboratories commented in response to a press release issued by
UNAIDS that Nonoxynol-9 may raise the rate of HIV infection rather than lower it.
In the study, it was reported that Advantage-S is a sustained and controlled release formulation containing 52.5 MG of N9 per dose initially designed to be
used once daily. WHO/UNAIDS conducted and published a study
demonstrating it was safe to use at that dose (AIDS 1998, 12:433-437).
This was misleading. Subsequently, a safety trial was conducted by UNAIDS administering the
product four times per day in female sex workers and it again was
judged to be safe.
In the UNAIDS Phase III clinical trial no upper
limit was put on dosing. In fact, the protocol encouraged women to use
the product after each act of intercourse, which ranged from 0-20 per
day. Women who used the product per-protocol may have used 10 or even
20 doses in a day. At this dose, previous studies have shown that N9
causes local lesions and is probably unsuitable as a microbicide.
Advantage-S was designed to avoid this problem and by not limiting the
dose to that which was tested and shown to be safe, the study
encouraged women to dose themselves to a toxic level.
"Before UNAIDS condemns N9 per se or Advantage-S, careful analysis
of the data should be conducted to see if there is a correlation
between the dose administered and the increased risk of transmission
of HIV," commented William J. Bologna, Chairman and CEO of Columbia
"The maximum tolerated dose that was studied in this population
was four times per day. Under no circumstances should this dose have
been exceeded. Despite this the investigators allowed and even
encouraged women to dose themselves to known toxic levels. The most
disturbing aspect of this study is that the statistical design was two
tailed. This means that it was anticipated from previous studies that
a toxic dose of N9 could be reached and thus, when a difference was
seen in the interim analysis, the Drug Safety Monitoring Board (DSMB)
was obliged to ensure that it was the active group and not the placebo
that had a lower incidence of transmission. Their failure to do so is
unpardonable and unethical. UNAIDS and the DSMB they appointed may
have been grossly negligent in the manner in which they designed and
monitored this study."
Columbia Laboratories, Inc. today for the appointment of a
team of outside experts to be given unfettered access to all the data
from this study and to report their independent findings to the public
at large. It is the Company's belief that this is the only manner in
which the women who are the victims of this epidemic can be