VANCOUVER, B.C. _ The AIDS virus can be nearly eradicatedfrom the body long-term, according to new data released hereThursday from a study that used a triple-drug regimen.
Hitting the AIDS virus early in the course of infection with acombination of the protease inhibitor Ritonavir, AZT and 3TC hasshut down viral replication in nine newly infected patients for nearlya year, setting the stage for the infection to burn itself out as infectedcells die off.
David Ho, director of the Aaron Diamond AIDS Research Center, inNew York, cautioned that the report represents a preliminarysnapshot of an "experiment in progress" and not a cure. In addition,no one knows how patients with advanced disease will respond totherapy.
In newly infected patients, however, HIV infection could literallyburn itself out within two to three years. He bases this prediction onthe number of infected cells and the time it takes for cells to die off,making way for new uninfected cells.
"We're seeing a very potent antiviral effect," he said.
"We put out the fire," said Martin Markowitz, also of the AaronDiamond Center and the lead investigator on the study. "If we lookfor virus in the blood, we can't find it. We are unable to grow virusout of a large pool of infected cells."
Markowitz told the XI International Conference On AIDS that theratio of CD4 and CD8 cells, which typically invert in AIDS patients,normalizes, which suggests that the crippled immune system mayhave revived in the absence of virus. Another promising sign thatHIV is disappearing in these patients is their antibody production hasbegun to decline.
The plasma levels of HIV1 in the nine patients, enrolled betweenAugust 1995 and February 1996 dropped 100-fold in the first twoweeks, Ho said. They were and continue to be given 200 mg of AZTthree times a day, 150 mg of 3TC and 600 mg of ritonavir twice aday. Therapy will continue for a minimum of one year.
Researchers said participating patients had tens of thousands ofvirions in the blood. For instance, one of the patients had nearly onemillion copies of virus per milliliter. By day 180, there were fewerthan 25 copies per milliliter.
All of the recruits were gay men with a mean age of 34, they rangedin age from 22-51. Twelve were initially recruited and three droppedout or were excluded.
Markowitz likened AIDS to a brush fire, in which CD4 cells are thefuel. To quench every last ember, he said, it's necessary to douse thefire with the most powerful combination of drugs possible. If a singleember remains, the infection may flare up again.
Ultimately, the best medical analogy for AIDS may be pediatricleukemia, a disease that is curable if chemotherapy succeeds inkilling off enough cancer cells, he said. But chemotherapy sometimesfails because it can't reach cancerous cells sequestered in the centralnervous system and testicles, which are so well guarded they areconsidered "immunologically privileged."
Within two months, the researchers hope to obtain the subjects'permission to conduct lymph node biopsies, which will enable themto determine whether the nodes serve as hidden reservoirs ofinfectious HIV. To get at sequestered sites like the brain and testicles,researchers may ultimately have to find a way to deliver anti-HIVdrugs directly into infected tissues, but those efforts still are sometime off, Markowitz said.
Another crucial question is when _ or whether _ to discontinuetherapy. A study of pediatric AIDS found that combination therapyhas succeeded in clearing HIV virus from their blood and restored anormal antibody profile. In these children, therapy has beendiscontinued without rekindling HIV infection.
The flurry of antiviral successes reported at the conference has raiseddifficult issues about how to use the new drugs in clinical settings toachieve the best effects. A meeting on this question by theInternational AIDS Society on Wednesday evening failed to yield aconsensus. Markowitz said he favors using the most powerfulcombination of drugs as soon after infection as possible. "You don'twant to use a glass of water or a garden hose _ you want to use a firehose and keep the water coming to put out every last ember,"Markowitz said. "There's no such thing as a partial response to HIVinfection. Otherwise, you invite the development of resistance."
He conceded, however, that "it's a little premature to get people in aroom and come to a consensus," adding that there are still far toomany unknowns about the new drugs and how they will function overtime. None of the studies reported at the conference have involvedsufficient numbers of patients or lasted long enough for firmconclusions to be drawn. n
-- Steve Sternberg Special To BioWorld Today
(c) 1997 American Health Consultants. All rights reserved.