Anti–retroviral drug cocktails have turned HIV from an immediate death sentence to a more chronic disease. But are patients starting therapy too late?
Two recent analyses, published in The Lancet and The New England Journal of Medicine, say that patients who start on antiviral drugs sooner live longer. The research could lead doctors to prescribe AIDS–fighting drugs far sooner, perhaps even when patients first test positive for the virus, thereby increasing the size of the $8 billion market for HIV drugs.
“Both studies say you should start earlier then the current recommendations advise,” says Dominique Costagliola, an epidemiologist at INSERM in Paris who co–authored the Lancet report. “We don't have the data to show it, but more and more it may be better to start as soon as you're positive.”
Earlier use of antiviral drugs like Viread, Sustiva and Combivir would boost sales for their makers. The biggest winner would likely be Foster City, Calif.–based Gilead Sciences (GILD – news – people), the second–biggest biotechnology company by market capitalization, which gets 80% of its sales from its stable of HIV medicines, including Viread. (See “The Profit Pill.”) Merck (MRK – news – people), of Whitehouse Station, N.J., New York's Bristol–Myers Squibb (BMY – news – people) and London's GlaxoSmithKline (GSK – news – people) might also benefit.
The severity of HIV infection is measured by a count of white blood cells expressing a protein called CD4 (for cluster of differentiation 4). A healthy person's CD4 count is around 900 cells per microliter, but current guidelines don't recommend treating patients until their CD4 counts have fallen below 350 cells per microliter. This level is actually lower than in the past, because doctors believed that waiting would spare patients side effects and prevent the HIV virus from becoming resistant to the drugs.
But the NEJM study, published April 2, found that patients who waited until their CD4 counts were below 350 had a 69% greater risk of death than those who did not wait. And there appeared to be added benefit to starting even earlier. Although the absolute difference in risk was smaller, patients who chose to start drug therapy when their CD4 counts were above 500 were half as likely to die as those who waited to start taking medicines.
In the Lancet study of 45,000 patients, published last Wednesday, starting drug therapy when CD4 counts were between 251 and 350 resulted in a 28% higher risk of AIDS and death than starting when CD4 counts were between 350 and 451.
Neither of the studies is a randomized trial, the gold standard of medical evidence in which patients are assigned to one treatment course or another. Instead, the studies compared people who decided to wait with those who didn't, and tried to adjust for differences between them statistically. The National Institutes of Health is beginning a big study, known as START, that will test whether patients benefit from beginning therapy earlier.
In a report to investors, Mark Schoenebaum, the biotechnology analyst at Deutsche Bank ( DB - news - people ), wrote that “momentum is building” for a change to treatment guidelines, and that the potential upside to Gilead, the leading maker of AIDS drugs, is underappreciated.
The change may also be driven by a dawning realization that the side effects of HIV drugs are less worrisome than the long-term effects of the HIV virus. Authors of both papers say that there is an increasing realization that the virus itself, by chronically amping up the immune system, damages the body even before it causes AIDS, leading to an increased risk of heart attacks, cancer and other diseases.
And then there is another problem: Patients currently don't start taking drugs even as early as the current guidelines say they should.
“Our patients are coming into care way too late,” says Mari Kitahata of the University of Washington, the lead author of the New England Journal study. “The median cell count is in the 200 range. We need to educate people that they need to come into care earlier so we can make decisions about what's best for them.”
Many of the authors of both studies, including Costagliola, report receiving speaking fees or grants from drugmakers; Dr. Katihata does not report any financial conflicts.