Embargoed for release until 5 p.m (EST), Wednesday, Aug.
8
New medications are urgently needed for individuals
who have drug-resistant HIV, and academia, industry and government
must work together to bring them into the clinic, urged leading
AIDS researchers Dr. Julio Montaner of the University of British
Columbia and the Canadian HIV Trials Network and Dr. John
Mellors of the University of Pittsburgh in an editorial in
the Aug. 9 issue of the New England Journal of Medicine.
“Antiretroviral therapy is most effective the first time
it is prescribed,” wrote Drs. Montaner and Mellors in the
editorial. But in patients who have had previous exposure
to two or all three classes of drugs used in the “cocktails,”
the therapy is usually unsuccessful in suppressing blood levels
of HIV to undetectable levels, according to the authors. Lacking
more effective therapies, some health -care practitioners
abandon efforts to suppress HIV levels in these treatment-exposed
patients they say.
In Canada, thousands of people with HIV are no longer responding
optimally to available antiretroviral drugs; in the United
States and Canada, about 30 percent of treated HIV patients
fall into this category.
“The lack of new antiretroviral therapy options for the
most desperate patients not only represents a failure on the
part of the scientific, academic and governmental communities,
but it also sets the stage for a dangerous epidemic of drug-resistant
HIV,” said Dr. Mellors, professor of medicine at the University
of Pittsburgh School of Medicine and chief of infectious diseases.
Without medications to suppress HIV to undetectable levels,
the virus continually mutates into new forms that often do
not respond to available drugs. These drug-resistant forms
of the virus are then transmitted from one individual to another.
Some five to 10 per cent of newly diagnosed HIV-infected patients
in the U.S. are thought to have been infected with drug-resistant
forms of the virus.
Antiretroviral drug cocktails are made up of three classes
of drugs: nucleoside reverse transcriptase inhibitors, non-nucleoside
reverse transcriptase inhibitors and protease inhibitors.
A number of factors can lead to a patient’s inability to
get the most benefit from the drugs, including a severe decrease
in the immune cell counts, very high levels of virus in the
blood and less than perfect adherence to the strict and sometimes
difficult treatment regimen.
Without optimal exposure to the medication, viral levels
are not suppressed adequately (to undetectable levels), drug-resistant
virus evolves and the virus escapes the effects of the treatment.
Once drug-resistant virus emerges, it becomes more difficult
to treat because of cross-resistance between available drugs,
according to the authors. Specifically, a virus that has become
resistant to one drug most often shows at least some cross-resistance
to other members of the same drug class.
“Clearly we need more and better drugs,” said Dr. Montaner,
professor of Medicine at UBC and national co-director of the
Canadian HIV Trials Network, based at St. Paul’s Hospital,
Vancouver. “Furthermore, simply adding drugs to the antiretroviral
regimen does not help people with resistant HIV, and there
is potential for serious drug toxicity with so many medications.
Ideally we need to combine several new active drugs in the
new regimen. This often requires using several experimental
drugs together. This cannot be easily done in clinical practice.
Several therapies being tested show promise, among them the
protease inhibitor tipranavir and the fusion inhibitors T-20
and T-1249. If we fail to use them optimally, their promise
will be greatly reduced. “
But certain obstacles need to be overcome in the process
of optimally getting new drugs through development and into
the clinic according to the authors.
“First, there need to be stricter regulatory requirements
during testing. Currently, antiretroviral drugs are gaining
approval without ever having been tested on the patients who
need them most — those with drug-resistant HIV,” the authors
contend.
“Secondly, we need the simultaneous release of more than
one approved drug into expanded access programs. The practice
of staggering the release of new antiretroviral agents is
unacceptable, as it allows clinicians to add only one new
drug at a time to a failing treatment regimen. This promotes
failure of the single new drug and further drug resistance.
We need the ability to add several new drugs in combinations.”
-30-
