One Three-Drug Antiretroviral Regimen Works Better Than Others, Two Studies Show

One three-drug antiretroviral combination regimen works better in HIV-positive patients who have never been on treatment, compared with other drug combinations, according to two studies published in the Dec. 11 issue of the New England Journal of Medicine, USA Today reports (Sternberg, USA Today, 12/11). In the first study, Dr. Gregory Robbins of Harvard Medical School and colleagues conducted a randomized, partially double-blind trial to compare pairs of sequential three-drug regimens, beginning with a combination of zidovudine and lamivudine and either nelfinavir or efavirenz or a combination of didanosine and stavudine and either nelfinavir or efavirenz. Researchers administered the regimens to 620 subjects, following them for a median of 2.3 years (Robbins et al., New England Journal of Medicine, 12/11). In the second study, Dr. Robert Shafer of Stanford University Medical Center and colleagues conducted a multi-center trial comparing initial therapy involving four-drug regimens containing efavirenz and nelfinavir in combination with either didanosine and stavudine or zidovudine and lamivudine with treatment involving two consecutive three-drug regimens, the first of which contained either nelfinavir or efavirenz. Researchers administered the regiments to 980 subjects, following them for a median of 2.3 years (Shafer et al., New England Journal of Medicine, 12/11). Researchers in both international studies found that the three-drug combination of zidovudine, lamivudine and efavirenz "works better and longer, is easier to take and suppresses the virus more quickly," according to the AP/Houston Chronicle (Johnson, AP/Houston Chronicle, 12/10).

Durable and Tolerable
Researchers found that after 48 months, the zidovudine, lamivudine and efavirenz combination was "still working and tolerable" in 90% of the participants on that regimen, compared with between 60% and 70% of the participants taking other drug combinations, the Washington Post reports. The studies indicate that adding nelfinavir to the three-drug regimen does not measurably improve treatment, compared with the three-drug regimen alone. The studies also demonstrate that combinations including didanosine and stavudine caused more serious side effects than other drug combinations and therefore should not be used "unless absolutely necessary," according to the researchers (Brown, Washington Post, 12/11). Researchers found that four-drug combinations "have another drawback" because when all three classes of antiretroviral treatment are represented -- as they are in the four-drug combinations -- and when HIV becomes resistant to "any one of them, there's no unused drug class to fall back on," Shafer said, according to USA Today (USA Today, 12/11).

Reaction
Robbins said, "Until now, it has been unclear which sequences of antiretroviral regimens provide the greatest benefit to patients previously untreated," adding, "Findings from this and similar studies can help reduce some of the guesswork involved" (Fox, Reuters, 12/10). International Association of Physicians in AIDS Care President Jose Zuniga said, "It confirms what physicians have suspected for a long time. It's important to question and reexamine from time to time what become established standards of care on the off chance we're wrong" (AP/Houston Chronicle, 12/10). NIAID Director Anthony Fauci said, "These findings offer new insight into the most effective approach for treating previously untreated HIV-infected individuals. Through well-conceived, collaborative clinical studies such as this one, researchers are learning how to use the many anti-HIV drugs now on the market to provide the maximum benefit for the longest period of time" (NIAID release, 12/10).

Editorial
Dr. Paul Skolnik of Boston University Medical Center's Center for HIV/AIDS Care and Research writes in an accompanying editorial that the "best regimen for a patient may differ with his or her circumstances," according to the AP/Chronicle (AP/Houston Chronicle, 12/10). Skolnik says, "Perhaps, for individual patients, the exact balance of risks and benefits -- namely the chance for long-term viral suppression, the risk of certain side effects, the possibility of induction of drug resistance and the ability to adhere to a particular regimen -- is best addressed by open discussions between care providers and their patients." He adds that because drug resistance is "often the primary difficulty in devising" different drug regimens, further study should be conducted to examine "this possibility to determine the efficacy of regimens based on a potent, boosted protease inhibitor, or, if tolerable, a more complex initial regimen" (Skolnik, New England Journal of Medicine, 12/11).

NPR's "Morning Edition" on Thursday reported on the studies. The segment includes comments from Robbins and Dr. Kenneth Mayer, director of the Brown University AIDS Program (Wilson, "Morning Edition," NPR, 12/11). The complete segment is available online in RealPlayer.

Back to other news for December 11, 2003