The research is the first randomized, controlled trial of hydroxyurea in HIV combination therapy. Lupo and colleagues concluded that the addition of HU to ddI-containing regimens is a "safe and cost-effective alternative for the treatment of HIV infection, without notable adverse events."

Among patients taking the HU + ddI + d4T regimen, almost 80% had undetectable viral loads at 24 weeks. This was a significantly higher proportion than for the groups taking ddI +d4T or HU + ddI.

Hydroxyurea has been in use for more than 30 years, mainly to treat leukaemia, ovarian cancer and, more recently, sickle cell anaemia.

Lupo noted that "hydroxyurea has little or no effect by itself on HIV." Its observed potency in the trial, he said, was "synergistic", that is, the result of the drugs working together.

HU blocks a human enzyme called ribonucleotide reductase, which is essential for producing dNTPs, the building block proteins of DNA. The advantage of HU in HIV treatment is that, with fewer natural dNTPs available, the virus' reverse transcriptase will tend to make use of nucleoside analogue compounds such as ddI and d4T. But unlike natural dNTPs, the analogues force viral DNA chains under construction to terminate prematurely, thus blocking viral replication. Hence, the synergy of the three drugs.

Earlier clinical work in France and the US have also shown beneficial effects of HU in anti-HIV treatment.

HU is less expensive than most other drugs used in treating HIV infection, said Lupo. Thus, it could be made widely accessible, even to patients in countries with low budgets for HIV/AIDS treatment.

Lupo's on-going trial involves 183 participants not previously exposed to antiretroviral therapy. They are located in eight study sites in Argentina, Brazil, Canada and Mexico.

Steve Miles of the US presented results of an hydroxyurea trial at the opposite end of the clinical spectrum – as salvage therapy. The 18 subjects had all failed previous regimens and their virus was showing specific mutations indicative of multi-drug drug resistance. "In this case, the patients had no therapeutic options left," said Miles.

The salvage therapy used by Miles and his colleagues involved a triple combination: d4T, 3TC, and HU. It had potent beneficial effects on viral loads and body weight, despite the patients' resistance to other regimens containing d4T or 3TC. However, some patients experienced severe haematological toxicity, which could be related to the presence of the HU.

this story can also be found in  The Bridge, the onsite print newspaper

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