Triple Therapy Combats AIDS

A new approach to combatting HIV-1, the most common form of the AIDS virus, has been discovered by a team of Harvard researchers at the Massachusetts General Hospital (MGH).

Yung-Kang Chow, a fourth-year M.D./Ph.D. student at the Medical School, reports in the current issue of Nature that he was able to prevent the virus from duplicating and spreading to other cells through a new technique known as convergent combination therapy.

Ordinarily, an enzyme called reverse transcriptase allows the HIV virus to take over host cells' nuclei and manufacture new virus particles.

AZT and ddI, common anti-AIDS drugs approved by the FDA, can become ineffective because of the virus' capacity to mutate to forms not susceptible to the drugs.

Convergent combination therapy, never before used in the treatment of HIV infection, aims three different drugs at the enzyme and causes it to become dysfunctional. Though the virus is able to defend itself against each drug separately, the simultaneous action of three drugs over whelms the virus particle.

Chow and his colleagues found that AZT and ddI, added separately, caused the virus to mutate to different forms, but did little to halt its function.

But when they combined AZT, ddI and another reverse transcriptase inhibitor, pyridinone, the virus could no longer replicate and infect other cells.

"Although our strategy stopped viral replication in the laboratory, it is far too early to say how it will work in patients," Chow said in a statement. "But in the laboratory, it seems to work better than conventional combination therapy."

Chow added, "At the very least, we hope this new strategy will prolong the lives of people infected with HIV-1. Only time will tell."

Researchers cautioned in a statement released by MGH, however, that nothing is known about how the treatment will work in human patients. MGH will join the AIDS Clinical Trial Group, a major collaborative treatment group launched in 1986 by the National Institutes of Health, later this year and try the therapy experimentally in patients.

Martin S. Hirsch, MD, director of AIDS research at the MGH, called the therapy "an exciting new avenue of investigation."

"It may be years before this can be used in patients as regular treatment," Hirsch said. "What works in the laboratory does not always work as well--or sometimes at all--in patients. There's always the potential that these drugs will interact in unfavorable ways that we don't even understand yet.

Chow and his colleagues found that AZT and ddI, added separately, caused the virus to mutate to different forms, but did little to halt its function.

But when they combined AZT, ddI and another reverse transcriptase inhibitor, pyridinone, the virus could no longer replicate and infect other cells.

"Although our strategy stopped viral replication in the laboratory, it is far too early to say how it will work in patients," Chow said in a statement. "But in the laboratory, it seems to work better than conventional combination therapy."

Chow added, "At the very least, we hope this new strategy will prolong the lives of people infected with HIV-1. Only time will tell."

Researchers cautioned in a statement released by MGH, however, that nothing is known about how the treatment will work in human patients. MGH will join the AIDS Clinical Trial Group, a major collaborative treatment group launched in 1986 by the National Institutes of Health, later this year and try the therapy experimentally in patients.

Martin S. Hirsch, MD, director of AIDS research at the MGH, called the therapy "an exciting new avenue of investigation."

"It may be years before this can be used in patients as regular treatment," Hirsch said. "What works in the laboratory does not always work as well--or sometimes at all--in patients. There's always the potential that these drugs will interact in unfavorable ways that we don't even understand yet.