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integrase inhibitor powerful monotharpy studied 2 reduce side effects toxicity

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bimazek:
integrase inhibitor as a monotherapy reduces side effects and toxicity,

 integrase enzyme unlike protease nuke and nonnuke enzymes does not exist in human cells so inhibiting integrase enzyme does not have human side effects as much... this is my laymans understanding of the science

New Drug Offers Promise As Single Treatment For HIV
Main Category: HIV / AIDS News
Article Date: 17 Dec 2006 - 0:00 PST

An experimental antiretroviral drug designated "MK-0518" integrase inhibitor rapidly achieves sharp reductions in human immunodeficiency virus (HIV) levels, and may offer the prospect of single-drug treatment for patients with HIV infection, according to a Rapid Communication in the December 1 issue of JAIDS: Journal of Acquired Immune Deficiency Syndromes.

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.

About JAIDS

JAIDS: Journal of Acquired Immune Deficiency Syndromes (http://www.jaids.com) is an interdisciplinary journal co-edited by the foremost leaders in clinical virology, molecular biology, and epidemiology. It provides a synthesis of information on HIV and AIDS from all relevant clinical and basic sciences. Under the guidance of an eminent international editorial board, this groundbreaking journal brings together rigorously peer-reviewed original articles, reviews of current research, and results of clinical trials.

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