United Press International; Thursday February 5 2:02 AM EST
Ed Susman, UPI Science News

Dr. Franco Lori, scientific director of the Research Institute for Genetic and Human Therapy at Georgetown University, Washington, says, "We are quite excited about hydroxyurea. We've seen excellent results with some patients achieving reductions in viral load so low that even most sensitive assays cannot find the virus."

Lori tells United Press International that hydroxyurea (Hydrea, Bristol-Myers Squibb, Princeton, N.J.,) "is a suitable drug for long- term treatment. Hydroxyurea is an attractive option in AIDS therapy because it inhibits the multiplication and growth of infected cells. We have found hydroxyurea to be synergistic with other anti-AIDS drugs in suppressing reproduction of the virus."

Hydroxyurea, available from many suppliers, is expected to cost less than $1,000 a year. Treatment with protease inhibitors costs more than $4,000 a year. Using Lori's strategy, hydroxyurea and an anti-retroviral such as didanosine (ddI) target quiescent AIDS virus lurking in cells. At the same time another drug such as stavudine (d4T) or a protease inhibitor would track down and kill actively reproducing virus.

In one of several studies on hydroxyurea presented at the conference, Lori says all 24 patients on a therapy including hydroxyurea, ddI and the protease inhibitor indinavir saw their virus levels go below detectable limits _ and the effect was sustained for at least 11 months.

Lori notes, "There were few toxicities with hydroxyurea. We've been using the drug in cancer patients for 35 years and we use a much lower dose in treating patients with the AIDS virus."

However, other AIDS researchers say that further studies are needed before hydroxyurea is ready for prime time.

Dr. John Mellors of the University of Pittsburgh Medical Center, and a leading AIDS researcher, said, in a press conference, "We feel the information is not yet sufficient to recommend hydroxyurea."

Mellors says he's particularly concerned that the fall in circulating virus associated with use of hydroxyurea is not reflected by a rise in one marker of immune system regeneration, the white blood cells known as CD4 cells.

Mellors suggests that the failure of the CD4 cells to rebound as virus levels drop means something untoward might be occurring in treatment.

Dr. Bernard Hirschel, head of the AIDS/HIV unit at Hopital Cantonal, Geneva, Switzerland, another hydroxyurea researcher, argued that while it's true the CD4 rebound is not robust, "in a population of patients that we are treating with hydroxyurea, a large increase in CD4 cells may not be clinically important." For patients who are sicker than the group being treated, Hirschel would avoid hydroxyurea. Patients in his trials still have intact immune systems.

Lori says his studies show that hydroxyurea treatment modestly increases CD4 cells and also improves other immune system parameters.

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