BOSTON — Several promising, large-scale trials
trying to prevent the spread of HIV have produced sobering results,
as researchers discussed at a meeting last week, but longer-term
data on new treatments are proving encouraging.
Much of the buzz
at the 15th Conference on Retroviruses and Opportunistic Infections,
the largest yearly scientific meeting on HIV and AIDS, centered
on further analyses of a Merck & Co. vaccine
trial known as STEP. The trial was stopped last fall because
more people in the vaccine group got infected with HIV than in
the placebo group.
"The whole field of HIV research is really going in the right
direction, with I think the one exception of not making any tangible,
major league headway in vaccines," said Dr. Anthony Fauci, director
of the National Institute of Allergy and Infectious Diseases.
Scientists
at Merck and collaborating institutions went back through demographic
data of the 3,000 participants and ran extensive tests looking
for differences in immune cell response but found no "smoking
gun," said Dr. Susan Buchbinder, a San Francisco
Department of Public Health researcher who presented results
from the analysis.
They noticed that previous exposure to adenovirus,
the virus modified to carry three parts of the HIV genome in
the vaccine, increased the risk of infection. But, surprisingly,
an even greater association was seen with circumcision status,
Buchbinder said.
Volunteers who were not circumcised in the vaccine
group were nearly four times more likely to get infected than
those who got a placebo shot.
Buchbinder said her group has not
figured out why circumcision appears to play a role, but previous
research has shown that some cells on the foreskin are particularly
vulnerable to HIV infection.
The STEP trial marks the third human
vaccine that has failed. "I'm
not sure having a fourth, fifth, sixth and seventh efficacy trial
that doesn't work is very useful to us," said Ron Desrosiers,
chairman of microbiology at Harvard Medical School. "Maybe now
is the time to step back and make some creative discoveries and
come up with novel ideas."
Some patient groups and doctors were
also hoping for a success in reducing HIV infections by suppressing
herpes simplex 2. But in a study of 3,251 people infected with
that virus but not with HIV, there was no significant difference
in the number of HIV infections in patients who received the
herpes drug acyclovir and those taking a placebo after about
18 months, said the University of Washington's Dr. Connie Celum,
lead author on the study.
"There was a strong basis to think having herpes increases
risk for contracting HIV and transmitting it to partners," said
Paul Dalton, of Project Inform, a treatment and advocacy group
in San Francisco. "The herpes data I saw was very disappointing."
Even
as these setbacks led to a subdued feeling about prevention,
the mood on therapeutic treatments was optimistic, said Dr. Robert
Schooley, a researcher from UC San Diego.
Longer-term data on
drugs in new classes, such as Merck's Isentress, show them to
be "just as good as we thought they were," said
Schooley, who wasn't involved in Isentress research reported
at the meeting.
Even after 48 weeks, about 60% to 65% of patients
with a drug-resistant virus that added Isentress to their regimen
reduced the amount of virus in their blood to undetectable levels.
Of patients who added a placebo to their drug regimen, 31% to
35% reduced the virus in their blood to that level. Side effects
were minimal.
Dr. John Mellors, an infectious-diseases specialist
at the University of Pittsburgh who helped plan the scientific
program, said that though there were fewer blockbuster studies
to report at this year's conference, he didn't feel pessimistic
about the future of AIDS. "Research is ongoing," he said.