VANCOUVER, B.C. _ Combination therapy with antiretroviraldrugs holds the promise to defer disease progression and reduce viralload in infected patients to non-detectable levels. This encouragingnews heralds the second decade of scientific research on AIDS.

These were the opening remarks of Scott Hammer, director of theResearch Virology Laboratory at the Deaconess Hospital andHarvard Medical School, in Boston, in his lecture to lead off thescientific sessions at the XI International Conference on AIDS hereMonday.

Hammer said there has been a growing list of accomplishments whichhas contributed to a renewed sense of optimism and hope that greatercontrol of HIV disease can be achieved.

Without doubt the era of zidovudine monotherapy as a standard ofcare is now at an end, he said.

One of the most significant developments contributing to this is thesuccessful introduction of protease inhibitors that are designed tostop HIV in its tracks by inhibiting its protease enzyme. (See thestory on p. 1.)

HIV-1 protease performs a critical function; namely, cleaving thepolyprotein precursors that ultimately become the core proteins andenzymes of mature virions. In addition to having these new drugs,Hammer identified the new ability to monitor viral load, through theavailability of HIV RNA testing, as being a critical step in monitoringtreatment regimens much more precisely than has been possible in thepast.

In reviewing clinical data to date, Hammer said a number ofimportant lessons have been learned so far and these include that, forthe drugs tested, potent suppression of virus replication to levelsbelow detection in plasma can be achieved. In addition, impressiveCD4 cell increases in the order of 100-200 cells/mm3 which aredurable over months have been reported and that prevention ofresistance is achievable by potent virus suppression.

The hypothesis that eradication of virus is potentially attainable, astatement that six months ago might have seemed impossible, nowappears to be an acceptable concept and amenable to scientific test,Hammer said. However, the current wave of optimism needs to bekept in perspective.

"Any notion that we have arrived at a solution needs to be avoided,"Hammer said. "The recent advances that we have witnessed, on thecontrary, should spur even more intensive drug development effortsand the testing of aggressive treatment approaches."

Speaking at a sunrise breakfast satellite symposium titled RecentAdvances in Combination Antiretroviral Therapy, Michael Saag,senior scientist and associate director for Clinical Care andTherapeutics at the University of Alabama at Birmingham AIDSCenter, said a major limitation of protease inhibitors in clinicalpractice is the development of isolates and reduced susceptibilitywhile patients are receiving drug. This development is especiallyrapid when protease inhibitors are used as monotherapy and, hespeculated, when viral replication is less complete.

Therefore, when protease inhibitors are used, they should be used incombination regimens that reduce viral load in plasma toundetectable levels and sustain this effect for extended periods oftime.

Saag said the growing array of antiretroviral drugs now availablemeans it matters how AIDS is treated, especially since these newtherapies are considerably more potent. The data so far showscombination therapy provides substantial results. However, the taskwill be to determine in which sequence these drugs should be used. n

-- Peter Winter Special To BioWorld Today

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