U.K. Guidelines Restore First-line Status to Epzicom (abacavir/lamivudine) but Include a Cautionary Note

The final version of the 2008 British HIV Association (BHIVA) antiretroviral treatment guidelines restores abacavir plus lamivudine -- the 2 drugs in the fixed-dose Epzicom pill -- as a suitable first-line nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) backbone in HAART regimens.

In the draft of the guidelines, only tenofovir plus emtricitabine -- the drugs in the fixed-dose Truvada pill -- were recommended as a first-line regimen in combination with efavirenz (Sustiva); all 3 drugs are combined in the Atripla pill. In the draft, Epzicom was designated as an "alternative" to Truvada.

However, the final BHIVA guidelines emphasize that Epzicom should be used only by patients who are confirmed to be HLA-B*5701-negative. The HLA-B*5701 genetic test is highly accurate in showing which individuals are susceptible to abacavir hypersensitivity reactions.

Further, the guidelines state that Epzicom should be used "with caution" in patients with a baseline viral load > 100,000 copes/mL and in those at "significant risk" for developing cardiovascular disease.

An independent Data and Safety Monitoring Board recently recommended changes to the ACTG 5202 trial after interim results indicated that Epzicom did not suppress HIV as well as Truvada when combined with either efavirenz or boosted atazanavir (Reyataz) in patients with a high baseline viral load.

At the Conference on Retroviruses and Opportunistic Infections this past February, researchers with the large D:A:D study raised concerns about an elevated risk of heart attacks in people taking abacavir, although manufacturer GlaxoSmithKline did not detect a higher rate in more than 50 of its trials of the drug.

In addition to "equalizing" Epzicom and Truvada as a part of first-line therapy, the final BHIVA guidelines also recommended that HAART should be initiated in all HIV patients with fewer than 350 cells/mm3, matching the threshold put forth in the current U.S. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents.

However, according to the BHIVA guidelines, antiretroviral treatment may be started or considered before the CD4 count falls below 350 cells/mm3 in a small number of patients, including the following:

• People with an AIDS diagnosis (e.g. Kaposi's sarcoma) or any HIV-related co-morbidity;

• People with a low CD4 percentage (e.g. < 14%, where PCP prophylaxis would be indicated);

• People with hepatitis B virus (HBV) infection for whom treatment of hepatitis B is indicated;

• People with hepatitis C virus (HCV) infection in some cases where treatment of hepatitis C is deferred;

• People with established cardiovascular disease or with a very high risk of cardiovascular events (e.g., Framingham cardiovascular risk > 20% over 10 years).

The complete PDF version of the updated BHIVA guidelines are available online.

7/11/08

Reference
BG Gazzard (on behalf of the BHIVA Treatment Guidelines Writing Group). British HIV Association guidelines for the treatment of HIV-1-infected adults with antiretroviral therapy 2008.