New Gold Standard for Initial Antiretroviral Treatment of HIV Infection

An international team of AIDS researchers at Johns Hopkins and other institutions has found that a once-daily combination of three antiretroviral drugs works better as an initial treatment for HIV infection than another three-drug combination long considered the gold standard.

Reporting in the Jan. 19 issue of The New England Journal of Medicine, the researchers showed that after one year of treatment, a regimen of antiretroviral pills, called tenofovir DF (Viread) and emtricitabine (Emtriva), plus efavirenz (Sustiva), led to 14 percent more patients able to suppress levels of the virus, with fewer problems of anemia, fatigue and nausea than another widely used combination of antiretrovirals, zidovudine and lamivudine (AZT and 3TC, or Combivir), plus efavirenz.

"The implications are quite clear for patients with HIV who are about to start therapy: The simple combination of tenofovir and emtricitabine, plus efavirenz, is likely to be highly potent with minimal side effects or long-term toxicity," says the study's lead author, Joel Gallant, M.D., M.P.H., associate professor and associate director of the AIDS Service at The Johns Hopkins University School of Medicine. Gallant notes that this regimen became even simpler in 2004, when tenofovir and emtricitabine were combined into a single pill, called Truvada.

The U.S. Centers for Disease Control and Prevention estimate that 40,000 Americans are newly infected each year with the virus that causes AIDS. Another quarter- million people already have HIV and are unaware of their infection and need for treatment.

Gallant cautions that the latest results may not apply to those patients already on zidovudine-lamivudine therapy and experiencing no problems. However, he points out that after the first year of the study, expected to continue for another two years, data already show early evidence of lipoatrophy (fat loss) in patients taking this regimen. Lipoatrophy is a known complication of some HIV medications that can lead to disfiguring changes in body shape. The researcher says that if fat loss gets worse during the remainder of the study in patients taking the zidovudine-lamivudine regimen, this would support switching to the tenofovir-emtricitabine regimen.

Tenofovir DF and emtricitabine are relatively new drugs, approved by the U.S. Food and Drug Administration (FDA) in 2001 and 2003 respectively. Zidovudine was the first antiretroviral drug, approved in 1987, and lamivudine became available in 1995. Since 1998, zidovudine and lamivudine have been available in a single-pill formulation called Combivir, which is prescribed as one pill taken twice daily.

In this study, both combinations included efavirenz, which, like the other drugs, prevents the genetic material, or RNA, in HIV from being turned into DNA. Efavirenz has been widely used for initial therapy since its approval in 1998.

Gallant's study results are believed to be the first to demonstrate superiority of any regimen over the combination of zidovudine, lamivudine and efavirenz, which has been a popular and recommended combination for many years. The latest guidelines from the U.S. Department of Health and Human Services, released in 2005, recommend either combination as preferred initial treatments for HIV disease.