HYDROXYUREA (Hydrea?)

WHAT IS HYDROXYUREA?
Hydroxyurea (Hydrea?) is a drug used for antiretroviral therapy (ART). It is manufactured by Bristol-Myers Squibb. Hydroxyurea is sometimes referred to as HU.

Hydroxyurea was approved for use against cancer. It also works against sickle cell anemia. Hydroxyurea has not been approved by the FDA for use against HIV.

Hydroxyurea blocks an enzyme produced by human cells. This enzyme makes building blocks used by cells that are multiplying. Cancer cells multiply very quickly, so when hydroxyurea blocks this enzyme, the cancer grows more slowly.

These building blocks are also used by HIV when it multiplies. Some of the drugs used against HIV (the nucleoside analog reverse transcriptase inhibitors) are "fake" versions of these same building blocks. When HIV uses the fake materials, it can't multiply.

When hydroxyurea reduces the amount of "real" building blocks, then HIV is forced to use more of the "fake" versions: the anti-HIV drugs. Even though hydroxyurea does not attack HIV directly, it can make some anti-HIV drugs work better. Hydroxyurea works very well with the drugs ddI and d4T.
WHO SHOULD TAKE HYDROXYUREA?

Hydroxyurea has been studied in combination with the drugs ddI and d4T. Hydroxyurea is not recommended as part of ART against HIV. It reduces gains in CD4 cells, increases ddI's side effects, and can cause serious birth defects.

There are no absolute rules about when to start ART. You and your doctor should consider your CD4 cell count, your viral load, any symptoms you are having, and your attitude about taking HIV medications. Fact Sheet 404 has more information about guidelines for the use of ART.
WHAT ABOUT DRUG RESISTANCE?
The HIV virus is sloppy when it makes copies of its genetic code (RNA). This means that many new copies of HIV are slightly different from the original (mutations). Some mutations can resist an antiretroviral drug and continue to multiply. When this happens, the drug will stop working. This is called "developing resistance" to the drug.

Hydroxyurea blocks an enzyme produced by our own cells, not by HIV. This means that HIV can not develop resistance to Hydroxyurea. Taking hydroxyurea can slow down HIV mutations so that it takes much longer for resistance to develop to the other anti-HIV drugs you are taking.
HOW IS HYDROXYUREA TAKEN?
Hydroxyurea is available in 500 mg tablets. The most common doses studied have been 1 gram taken once a day, or 500 mg taken twice a day.

Scientists are working to find out the best dose of hydroxyurea for people with HIV. A study reported in 2002 looked at 600, 900, and 1200 mg daily. It also examined whether the doses should be taken once, twice or three times a day. The study found that 600 mg daily, taken as 300 mg twice a day, produced the best results in terms of tolerability and reduction of viral load.

A report in 2003 noted that the side effects of hydroxyurea could be reduced by using ddI in the enteric coated (EC) form, or using the chewable tablets twice daily, together with 300 mg of hyroxyurea twice a day.
WHAT ARE THE SIDE EFFECTS?
With the start of any anti-viral treatment there may be temporary side effects such as headaches, hypertension, or a general sense of feeling ill. These side effects are likely to get better or even disappear over time.

The most serious side effect seen with hydroxyurea is pancreatitis that caused some deaths. Hydroxyurea may cause nausea, vomiting, and diarrhea. It can also lead to weight gain, hair loss, and changes in skin coloring. It may cause birth defects, so pregnant women should not take hydroxyurea. It can also damage the bone marrow. This can result in anemia (a drop in the number of red blood cells) or neutropenia (a drop in the number of white blood cells).

Scientists reported in early 2000 that hydroxyurea appears to increase the risk of peripheral neuropathy.
HOW DOES HYDROXYUREA REACT WITH OTHER DRUGS?
Hydroxyurea is most effective if taken with reverse transcriptase inhibitors such as ddI or d4T. However, hydroxyurea intensifies the side effects of ddI.

Hydroxyurea's side effects may be worse if taken with AZT, because both drugs can damage the bone marrow.