VANCOUVER, B.C. _ Questioning whether antiretroviral therapycan be effective and tolerated over the long haul, the two discoverersof the AIDS virus challenged researchers at the XI InternationalConference On AIDS to develop new, more natural approaches totreatment that are more affordable and less toxic.

"It is imperative for those of us in academic scientific centers tocontinue to aggressively pursue studies of the biology of this diseaseand to vigorously seek biological, natural means to control HIV,"said Robert Gallo, director of the Institute of Human Virology at theUniversity of Maryland in Baltimore. "In doing so we will have back-up therapy for these chemical approaches, and probably with less, orperhaps even no, toxicity."

Recent treatment advances generated by protease inhibitors haveencouraged researchers to compare future HIV treatment to thesuccessful approaches of cancer chemotherapy, which often requiresa combination of drugs administered during an extended maintenancephase. Nonetheless, many cancers eventually resist drugs, manypatients cannot tolerate their toxicity and the drugs can inducesecondary diseases, such as other cancers, Gallo said.

Likely faced with a similar dilemma, AIDS researchers should searchfor biological agents that would serve as a back-up to antiretroviraltherapy and other chemical approaches, he said.

"I don't say stop [chemical approaches], but let's explore the basicunderstanding of the virus interaction with the immune system andhow the virus causes disease," Gallo said.

One such biological approach Gallo's lab developed last yearinvolves the anti-HIV effects of chemokines, a subclass of cytokines.Upon discovering three chemokines that appear to block HIV entryinto cells, Gallo's lab has been using genetic manipulation to exploitthe anti-HIV effects of chemokines. By inducing the production ofchemokines, viral infection might be prevented, he added. Indeed,Gallo presented unpublished data by Paris researchers showing thatsome hemophiliacs who were exposed to HIV-infected blood yetwere not infected had produced high levels of HIV-inhibitingchemokines.

"Their specificity and the fact that they open a new avenue makes thisapproach current and exciting," he said.

Another natural therapeutic approach that would be particularlyattractive to developing countries is development of gene therapy thatcould be administered into stem cells and act as a preventive vaccine,Gallo said. The possibility of preventing infection with a singleinoculation rather than requiring multiple follow-up treatments is animportant consideration in developing countries where health care isless accessible, he added.

Taking a different approach, Luc Montagnier, director of thedepartment of AIDS and retroviruses at the Pasteur Institute, in Paris,created the World Foundation of AIDS Research and Preventionthree years ago to develop timely combination therapy forasymptomatic HIV-positive patients who are at high risk forprogression to AIDS (i.e. high viral load, fast CD4 decline).

"Since sustained high viral load requires lymphocyte activation, webelieve that additional therapies against infectious co-factors thatcause immune activation and oxidative stress are required," he said."These treatments may reduce the required dose of antiviral drugs,decreasing their cost and toxicity as well."

Acknowledging that halting the AIDS epidemic requires preventivevaccines that could induce protection to the mucosal transmission ofthe numerous variants of HIV, Montagnier said current vaccinedevelopment is far from ideal. He proposed a more modest approachaimed to protect against disease rather than viral infection.

"If the viral load at the onset of infection is low, no disease willensue," he said. "There are several ways to explore this concept,including immunization against nef, tat, and gag proteins, and againstthe part of cellular co-receptors that are physiologically irrelevant butimportant for virus infection."

Montagnier suggested that these "vaccine" approaches could betested fairly fast by using them initially as therapeutic agents in HIV-positive persons. By measuring viral load and other immunologicalmarkers, researchers could evaluate the potential efficacy of suchimmunizations in newly infected persons.

In Other News From The Conference

* Abbott Laboratories, of Deerfield, Ill., said trials of its proteaseinhibitor, Norvir, (ritonavir) with Retrovir (AZT) and Hivid (ddC)showed the combination therapy kept HIV at undetectable levels in17 patients after 60 weeks of treatment and increased the CD4 T cellsto a mean of 337 from a mean baseline count of 155. AZT and ddCare nucleoside reverse transcriptase inhibitors. AZT is sold by GlaxoWellcome plc, of London, and ddC is sold by Roche Holding Ltd., ofBasel Switzerland.

* Agouron Pharmaceuticals Inc., of La Jolla, Calif., said studies of itsprotease inhibitor, Viracept (nelfinavir), with Retrovir (AZT) andEpivir (3TC) showed the combination therapy reduced HIV toundetectable levels in 11 AIDS patients after 16 weeks of treatment.The patients also experienced a mean increase of 100 CD4 T cells. At20 weeks no new HIV-related infections or tumors were found andimprovement was seen in other HIV-related conditions. AZT and3TC are nucleoside reverse transcriptase inhibitors sold by GlaxoWellcome plc, of London.

* Arkopharma, of Nice, France, has developed an anti-HIV drugderived from a boxwood evergreen tree extract. Clinical trialinvestigators said the drug, called SPV-30 extract, combined withantiretroviral treatments reduced HIV by 70 percent in 55 percent ofthe 400 AIDS patients who participated in an informal 6-monthstudy.

* Paracelsian Inc., of Ithaca, N.Y., said studies conducted by theNational Institutes of Health, of Bethesda, Md., demonstrate that theprotein c-mos kinase is expressed by CD4 T cells infected with HIVand that the enzyme is involved in replication of the virus and deathof T cells. C-mos kinase normally is activated in reproductive germcells, the company said. Paracelsian added it has a c-mos kinaseinhibitor in clinical trials. n

-- Skip Connett AIDS Alert Editor

(c) 1997 American Health Consultants. All rights reserved.