MK-0518

New Drug Offers Promise as Single Treatment for HIV.[India]
www.medindia.net, December 13, 2006.
http://www.medindia.net/news/view_news_main.asp?x=16668


India: An experimental antiretroviral drug designated
"MK-0518" rapidly achieves sharp reductions in human
immunodeficiency virus (HIV) levels, and may offer the
prospect of single-drug treatment for patients with HIV
infection.

If the good results are borne out by further studies,
"MK-0518 should clearly be a welcome addition to the existing
treatment options for those persons infected with HIV-1",
concludes the new study, led by Dr Martin Markowitz of The
Rockefeller University, New York.

Thirty-five previously untreated patients with HIV infection
were randomly assigned to receive one of four different doses
of MK-0518, or to receive an inactive placebo. After 10 days
of treatment, the patients' "viral load" was measured. The
viral load is a key test that determines how well HIV—the
virus that causes AIDS—is reproducing in the patient's body.
At the start of the study, all patients had a relatively high
viral load of 5,000 copies per milliliter of blood.

Patients taking MK-0518 had dramatic reductions in their viral
load. After just 10 days of treatment, viral load decreased by
an average of 98 percent (based on the logarithmic scale used
to measure HIV levels).

The results were similar across all four MK-0518 dose groups.
For most patients in each group, the viral load dropped to an
"undetectable" level of less than 400 copies per milliliter.

Treatment with MK-0518 was "generally well tolerated," the
authors write. Side effects such as headache and dizziness
occurred, but there were no major adverse effects.

Although major advances have been made in drug treatment of
HIV, new treatments are still needed for several reasons.
Current approaches require complex combinations of drugs, with
many short- and long-term toxic effects. Drug resistance is
also an increasing problem, as new strains of HIV become
resistant to the effects of current antiretroviral drugs.

There is special interest in MK-0518 because it works in a
different way than other anti-HIV drugs. Previous
antiretroviral drugs target enzymes called reverse
transcriptase and protease, which play key roles in the virus'
ability to reproduce itself.

MK-0518 targets a "third enzyme" called integrase, which is
found only in HIV and is essential to the virus' ability to
insert its DNA into human genes. By blocking integrase,
MK-0518 blocks HIV's ability to reproduce itself and infect
new cells. Because it works differently, MK-0518 should also
reduce interactions with other anti-HIV drugs.

Although preliminary, the study suggests that MK-0518 is a
potent, well-tolerated single-drug treatment that is highly
effective in reducing HIV viral loads, the investigators
conclude. Based on the successful results, a second phase of
the study—comparing various doses of MK-0518 with current
combinations of anti-HIV drugs—is already underway.