By Skip Connett

Special To BioWorld Today

GENEVA — As increased reports of adherence and toxicity problems have dampened the remarkable gains in HIV protease-inhibitor therapy, researchers at the 12th World AIDS Conference here presented a strong case for offering patients alternative options using two promising candidates from a different class of drugs.

And while this conference lacks the hyped-up treatment breakthroughs that marked the gathering two years ago, dramatic decreases in adult mortality and mother-to-child transmission underscore the scope of benefits gained since the Vancouver meeting in 1996.

"There isn't any loss of enthusiasm for what is being accomplished in care," said John Bartlett, chief of infectious diseases at Johns Hopkins University, in Baltimore. "The [U.S. Centers for Disease Control] surveillance data are very convincing in terms of reductions in mortality and opportunistic infections."

Although the 75 percent decline in AIDS mortality and morbidity seen in the U.S. over the past three years isn't shared by many countries, researchers reported significant drops in cases of mother transmitting the virus to infants in those countries where zidovudine (AZT) preventive therapy is available. AZT is sold by Glaxo Wellcome plc, of London.

By combining AZT prophylaxis with Caesarean section, transmission nearly was eliminated in a study of women in France, reported Lynn Moffenson, assistant chief of the Maternal and Child Health Branch at the National Institute of Child and Human Development in Bethesda, Md.

News of antiretroviral treatment options presented in Geneva took on added interest in light of the increased prevalence of drug resistance seen in patients on protease inhibitors.

How much resistance is due to poor adherence to regimens and how much to treatment failures is not clear, but researchers presented compelling data that other options are needed as patients face the prospect of extended therapy now that it is clear the virus cannot be completely eradicated.

Against that backdrop, follow-up studies were presented on two investigational drugs, abacavir, a nucleoside reverse transcriptase inhibitor manufactured by Glaxo, and efavirenz, a non-nucleoside reverse transcriptase inhibitor made by E.I. DuPont & Co., of Wilmington, Del.

New Drugs Could Affect Treatment Guidelines

Already cornering a large share of the HIV drug market with its two-drugs-in-one combination, combivir, Glaxo presented data showing that adding abacavir to the equation provides results as good as those seen with protease inhibitors. Company researchers also said the regimen is relatively easy to take and has few side effects or drug interactions. Combivir combines AZT and 3TC, two reverse transcriptase inhibitors.

"I think after Geneva there is going to be much discussion about treatment guidelines and abacavir is going to change the way that looks," said Neal Graham, Glaxo's director for HIV programs in the U.S.

For the first time, Graham said, three drugs in the same class have effectively reduced viral load in treatment-naive patients to levels that have been seen only in those on protease inhibitors.

"The data are fairly provocative because the early promise of the drug [abacavir] has been held up," he said. "We are seeing very good viral load responses with combivir and abacavir together."

Comparable results have been seen when efavirenz is combined with two other antiretroviral drugs. The drug suppressed HIV RNA levels to below detectable (less than 400 copies) levels in a greater percentage of patients than using a standard regimen containing a protease inhibitor, DuPont researchers reported.

In combination with AZT and 3TC, efavirenz more effectively suppressed HIV through 24 weeks compared with AZT, 3TC, and indinavir in 450 primarily antiretroviral-naïve patients. Glaxo sells 3TC and indinavir is a protease inhibitor sold by Merck & Co. Inc., of Whitehouse Station, N.J.

While Bartlett put both abacavir and efavirnez at the top of the list of exciting new drugs, he and other top AIDS experts cautioned resistance could develop more rapidly when treatment is limited to one class of drug.

"People here are saying three nukes are not going to do it [provide long-term suppression] — you need another point of attack," he said. "For some patients it may be preferable, but not for the majority." *