Newsday - July 31, 2002
Laurie Garrett, Staff Writer

If the model developed by the University of California at Los Angeles researchers holds up, it would mean the pandemic could be slowed, even eradicated, after 50 years of widespread use of anti-HIV drugs.

Based on controversial assumptions about the behavior of HIV and infected individuals, mathematician Sally Blower and her UCLA colleagues believe that, "the United States has a moral imperative to start pouring money into eradication throughout the world ... These drugs, even though they cannot cure individuals who are treated, could head us towards eradication," Blower said in an interview.

The UCLA model, which appears in today's issue of the British publication The Lancet Infectious Diseases, uses a mathematical method called "uncertainty analysis" to calculate the impact of a range of variables, offering possible outcomes from decades of use of anti-HIV drugs in San Francisco. And even making what Blower considers worst-case assumptions, such as the evolution of drug-resistant viruses that remain infectious and an increase in unsafe sexual activity among the treated individuals, the UCLA model predicts the drugs will stop the San Francisco epidemic well before the end of this century.

"That's with the current drugs," Blower concluded. "If you got better drugs - and we must assume that we will have better drugs soon - then things would come along much, much more quickly."

The primary problem with all mathematical models, experts say, is the validity of the assumptions built into them.

"Despite being a statistician I would argue against making public policy based on math modeling," mathematician Stephen Gange of Johns Hopkins School of Medicine said in an interview. "I think we all want to see the epidemic decrease, but using math models to get us there is stretching things a bit."

The UCLA team assumes anti-HIV treatments lower the amount of virus in the bloodstream by at least half and up to 100-fold. That means widespread use of the drugs leads HIV-positive individuals to actually be less infectious to their sexual partners. The UCLA team also assumes drug resistant strains of HIV will arise but will be less infectious.

But in their studies of patients in Uganda and America, Gange said, treatment only marginally affects a person's ability to infect.

Gange works with Dr. Ronald Gray, who has closely monitored the outcomes of HIV treatment at Johns Hopkins in Baltimore, in a national cohort of female patients in the United States and in a remote part of the East African nation of Uganda. Their data, crunched through Gange's mathematical models, suggests a different picture.

The Gray/Gange data, presented last month at the 14th International AIDS Conference in Barcelona, found that anti-HIV medicines decreased by an essentially insignificant amount the risk that any given individual might transmit HIV sexually. That modest effect "would be obliterated," Gray said, by the sorts of behavioral changes now seen in the United States, such as more unprotected sex.

The main reason treatment won't be enough to slow the epidemic, Gange said, is that in the real world, most patients manage to sustain a 50 percent or less reduction in viral loads - that's below the bottom end in the UCLA model.

Blower counters that her model is based on the experiences of physicians and patients in San Francisco, where about 70 percent of the HIV population is in treatment, and most have experienced decreases in their viral loads of more than 50 percent. She said any community that attains the same levels of treatment coverage should experience similar declines in HIV incidence over time. The San Francisco model, Blower said, "could be a global model."

In Gange's real world, most HIV-positive Americans remain untreated, mainly because they don't realize they are infected.

Blower concedes that if a small percentage of the HIV population is treated, "you'll have very little impact on transmission" of HIV. But, she counters, that is why you must aim for 90 percent coverage.

Whether or not anti-HIV drugs can reverse the epidemic, the UCLA and Hopkins groups believe the medicines should be available to all who need them, regardless of poverty because, Gange said, "they work. They extend people's lives. And that's impetus enough to have as a goal global access to the therapies."
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