14 Aug 2006

HIV combos compared

A four-drug "cocktail" to suppress HIV and prevent Aids is no more effective than a three-drug combination now widely used for reducing the debilitating effects of the virus, new research has concluded.

The study, published in the August 16 issue of the Journal of the American Medical Association and expected to be presented at the International Aids Conference in Toronto, found that an experimental four-drug combination was no more effective than a widely-used three drug set in controlling the onset of reducing blood levels of HIV, virological failure, adverse events or drug resistance. This has led researchers to recommend that the triple-drug regimen should continue to be the standard initial HIV treatment.

From 2001 to 2005, scientists from New York-Presbyterian Hospital/Weill Cornell Medical Centre in New York City conducted a double-blind, placebo-controlled study of 765 HIV-infected patients who had not previously received HIV treatment. The patients were randomly assigned to one of two regimens: a four-drug cocktail (zidovudine, lamivudine and abacavir and the non-nucleoside drug efavirenz), or a three-drug cocktail containing zidovudine, lamivudine and efavirenz.

More was considered better
The rationale for the study was simple, according to Dr Marshall Glesby, co-director of the HIV Clinical Trial Unit at the New York-Presbyterian Hospital/Weill Cornell Medical Centre. "In general, more has been better than less, with three drugs better than two and two drugs better than one," he said.

But about the same number of patients in both groups (88 percent of the four-drug group and 85 percent of the three-drug group) achieved undetectable blood levels of HIV. After a median three-year follow-up, 25 percent of the four-drug group and 26 percent of the three-drug group reached virologic failure, meaning the drugs could no longer reduce the levels of virus in the patient's blood. This was defined as two consecutive HIV-1 RNA levels of 200 copies per millilitre or more, a statistical stalemate.

The researchers also found no significant group differences in the time it took to reach virologic failure, increases in immune-system T cells or the incidence of side effects. "It's perhaps a little bit surprising that adding a potentially more potent therapy to the cocktail didn't result in a greater response," Glesby said. "But we're getting such good responses overall. That may be part of it as well."

One shoe does not fit all
Although this particular four-drug combination was no more effective than the three-drug combination, Glesby cautioned that the results couldn't be universally applied. Some patients need four-drug or even five- or six-drug combinations to achieve virologic success. "You can't necessarily say in general that four drugs are not better than three," he said.

The study "surely reinforces the three-drug approach for optimal efficacy and cost-effectiveness of antiretroviral therapy," said Dr Sten H. Vermund, director of the Institute of Global Health at the Vanderbilt University School of Medicine in Nashville, Tennessee.

"However, this should not be confused with the increasingly common use of four drugs for boosting the effect of a protease inhibitor to permit lower doses to be used," Vermund added. "The purpose for four drugs in that case is to reduce side effects and, therefore, increase adherence."

"These findings suggest that current triple-drug therapies continue to perform remarkably well for the large majority of patients. [But] every doctor has to treat patients on a case-by-case basis," Dr Roy M. Gulick, co-director of the HIV Clinical Trial Unit at the New York-Presbyterian Hospital/Weill Cornell Medical Centre and lead author of the study, said in a statement.

In a separate analysis, the researchers found that non-Hispanic black patients had a 66 percent higher risk of virologic failure than other patients.

Simple may be better
The August 16 issue of the Journal of the American Medical Association was published to coincide with the International Aids Conference. In another article published in the issue, researchers also reported that a simplified HIV treatment may be effective for some patients.

Researcher Susan Swindells, of the University of Nebraska Medical Centre in Omaha, conducted a pilot study in which 34 HIV-infected adults were treated with a single boosted protease inhibitor instead of the standard three-drug regimen for maintenance therapy. The 24-week study showed that 31 of the patients achieved virologic success.

"Maintenance therapy with a single boosted protease inhibitor offers a treatment strategy with potentially less complexity, pill burden, long-term complications and cost," Swindells and her colleagues wrote. "[But] larger randomised trials comparing this approach with standard antiretroviral therapy are warranted." – (HealthDayNews)