After years of despair, hope is returning to the lives of thousands of hiv-infected patients. The number of Americans newly diagnosed with aids in 1996 was 6 percent lower than in 1995—the first such decline ever—and the number of Americans who died of aids dropped a stunning 23 percent. The declines are due in part to a new class of antiretroviral drugs called protease inhibitors. This past year brought more evidence of their effectiveness.
In a report that appeared in Science in May, microbiologist Ashley Haase and his colleagues at the University of Minnesota Medical School in Minneapolis showed that a combination of three drugs, including the protease inhibitor Ritonavir, dramatically reduces virus levels, not only in the bloodstream but in the lymph nodes—the headquarters of hiv. Haase and his team biopsied the tonsils, which consist of lymph tissue, of hiv-infected patients. Over six months of triple-drug treatment, the researchers watched the virus count in the tonsils drop by more than 99.9 percent.
The staggering drop was a welcome surprise, says Haase, but it doesn’t show that the drugs can actually rid the body of hiv. For one thing, even after a 99.9 percent decline, 10 million potentially infectious viral particles remained in the patients’ lymph systems. For another, antiretroviral drugs do not kill infected cells; they only arrest the spread of infection by blocking the manufacture of new virus. The traditional anti-hiv drugs, such as azt, do so by blocking an enzyme the virus needs to copy its genetic material into the host dna. The protease inhibitors work by blocking the assembly of the virus itself. Both kinds of drugs leave cells that are already infected—whose dna already contains hiv genes—untouched. If all those cells had a short life span, Haase explains, eradication of hiv in patients on combination therapy might occur within a few years. But the life span of hiv-infected cells is not known. As long as any of them remain in the body, they can reignite the infection as soon as the drug treatment is stopped or—if drug-resistant virus crops up—even before.
The drugs are not yet a cure, then, but by controlling the infection, they allow the immune system to heal and T cell counts to rebound. And that may permit researchers to come up with ways of tweaking the immune system to detect and kill the remaining hiv-infected cells. Fred Valentine at New York University Medical School is beginning a clinical trial that will combine combination drug therapy with an hiv vaccine. Other groups are exploiting the new discoveries about hiv receptors to engineer viruses that may selectively enter only hiv-infected cells and kill them—or at least disable the hiv.
There are drawbacks to combination therapy. Some patients cannot tolerate the regimen or the drugs themselves. Others have developed hiv that is resistant to treatment. This usually occurs because of lapses in the drug regimen, or because patients have added a protease inhibitor after developing virus that is resistant to two or three other drugs. But the biggest problem of all is money: triple-drug therapy costs from $8,000 to $12,000 a year, to say nothing of laboratory and doctors’ bills.
If you’re poor, you are unlikely to reap the benefits of the revolution in aids treatment. In the United States, women are left out disproportionately: they now make up 20 percent of Americans with aids, but they are less likely to be diagnosed and treated than gay men because they are more likely to be badly educated, drug-addicted, burdened with children, and poor. In the developing world, where the number of hiv-infected people is still skyrocketing, gender is not an issue. In countries where people are still dying in even huger numbers from illnesses that could be prevented by clean latrines, combination therapy for aids remains a remote prospect for men and women alike.