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What is apricitabine?
Apricitabine is an experimental nucleoside reverse transcriptase inhibitor (NRTI).

Apricitabine is being developed by Avexa, an Australian pharmaceutical company. The drug was first developed by BioChem Pharma (where it was called BCH10618). BioChem Pharma was then sold the Shire Pharmaceuticals (where the drug was called SPD754). Shire then sold the rights to develop the drug to Avexa.

Apricitabine has not yet been evaluated or approved by the U.S. Food and Drug Administration.

What is already known about apricitabine?
Apricitabine is an anti-HIV medication. It is in a category of HIV medicines called nucleoside reverse transcriptase inhibitors (NRTIs). Apricitabine prevents HIV from entering the nucleus of healthy T-cells. This prevents the cells from producing new virus and decreases the amount of virus in the body.

Apricitabine will need to be used in combination with other drugs, including another NRTI and at least one protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI).

Apricitabine's chemical structure is similar to that of Epivir (3TC) and Emtriva (emtricitabine). A study has determined that Epivir can decrease the amount of apricitabine inside cells, meaning that apricitabine cannot be combined with Epivir or Emtriva.

The correct apricitabine dose has not yet been determined. It is also not clear if the drug will need to be taken twice a day or once a day.

Like other NRTIs, apricitabine might interact with other medications, including those used to treat HIV. It is important that your personal physician and/or the research nurse or study investigator be aware of all drugs you are taking, including those you buy without a prescription.

According to test tube studies, apricitabine may be active against strains of the virus already resistant to other NRTIs, including Retrovir (AZT) and Epivir. Early clinical trial results also suggest that it is active against Epivir-resistant HIV. Test tube studies also suggest that apricitabine can cause the K65R mutation, which can cause resistance to Videx (ddI) and Viread (tenofovir).

What has been learned from clinical trials?
Results from a ten-day study were reported in 2003. The study enrolled 63 HIV-positive patients who had not been on other anti-HIV medications in the past and had T-cell counts of 250 or lower and viral loads between 5,000 and 10,000. The patients took daily doses of apricitabine (without other HIV drugs) of 400, 800, 1200, or 1600mg or placebo. After ten days of apricitabine treatment, viral load decreases ranged from 1.18 log (in the lowest dose group) to 1.58 log (in the highest dose group), compared to no significant decrease in the placebo group.

Another ten-day study, reported in 2004, suggested that apricitabine (using doses of 200mg or 400mg twice daily) causes significant viral load reductions in patients with HIV containing mutations that cause resistance to currently available NRTIs.

Early results from an ongoing Phase IIb study have been reported by the developer. The study is comparing two doses of apricitabine (600mg or 800mg twice daily) to Epivir in treatment-experienced patients with HIV resistant to Epivir. In the first part of the study, patients remained on their failing treatment regimen (including Epivir) or switched their Epivir for apricitabine for a total of 21 days. After day 21, patients continue to receive either Epivir or apricitabine for up to 24 weeks, but are permitted to change their other antiretrovirals. After week 24, all patients will be switched off of Epivir and given apricitabine to use in its place.

During the initial 21-day study period, patients who received apricitabine achieved, on average, a viral load reduction of greater than 0.8 log compared to a reduction of less than 0.03 log in patients maintained on Epivir treatment. After 24 weeks, according to the manufacturer, more than 70% of those switching to either dose of apricitabine from Epivir had virus levels under 50 copies. Those switching also had CD4 increases averaging 150 cells. Viral load and CD4 count changes among those who remained on Epivir were not reported by the manufacturer.

What is known about side effects?
There is not a lot of information about the potential side effects of apricitabine. In the 63-person study reported to date, apricitabine was said to be well tolerated and did not cause any more (or more severe) side effects than those seen in patients in the placebo group.

After 21 days in the Phase IIb study, no serious side effects related to the study drug were reported, and no patients stopped treatment due to apricitabine-related side effects.

Who should not take apricitabine?
It is not known whether apricitabine will harm an unborn baby. It is very important to treat HIV/AIDS during pregnancy to reduce the risk of infecting your baby. Talk to your doctor about your treatment options.

It is not known whether apricitabine passes into breast milk and what effect it may have on a nursing baby. To prevent transmission of the virus to uninfected babies, it is recommended that HIV-positive mothers not breast-feed.