HIV

Paul Volberding C.C. Carpenter, M.A. Fischl, S.M. Hammer, M.S. Hirsch, D.M. Jacobsen, D.A. Katzenstein, J.S. Montaner, D.D. Richman, M.S. Saag, R.T. Schooley, M.A. Thompson, S. Vella, P.G. Yeni, P.A. Volberding, "Antiretroviral therapy for HIV infection in 1996--Recommendations of an international panel," JAMA-Journal of the American Medical Association, 276:146-54, 1996. (Cited more than 180 times since publication) Comments by Paul A. Volberding, chairman of the board of the International AIDS Society-USA and Director of the Center of Aids Research at the University of California at San Francisco. " . . . we got criticized by some sides for being too aggressive, and from some for not being aggressive enough." --Paul Volberding Rules are made to be broken--or, in this case, amended and improved. The members of the International AIDS Society-USA (IAS), a national not-for-profit organization based in San Francisco, embarked on this 1996 study in response to HIV treatment guidelines that they believed to be seriously out of date. The study's objective was to "provide clinical recommendations for antiretroviral therapy for human immunodeficiency virus (HIV) disease with currently (mid-1996) available drugs." The 14-member IAS expert panel addressed when to start therapy, what therapy to start, when to change therapies, and what therapy to use. Widely regarded as a success, the study has been updated in a 1997 paper (C. Carpenter et al., JAMA-Journal of the American Medical Association, 277:1962-9, 1997) and again in another paper due out in JAMA this summer. "When we started, we thought the government had been somewhat too slow," explains senior author Paul A. Volberding, a professor of medicine and director of the Center of Aids Research at the University of California at San Francisco, director of the AIDS program at San Francisco General Hospital, and chairman of the board of the IAS. Volberding notes that the Centers for Disease Control and Prevention hadn't published antiretroviral guidelines since 1993. "As a result, I think, in part, of our panel publication," he continues, "the government actually organized a more strenuous effort and has also now published its own set of guidelines, ... which fortunately are very similar to our latest." According to Volberding, the paper is something of milestone in the area of HIV therapy. Published at a controversial time in the epidemic, it was the first to formally introduce the protease inhibitor as a viable treatment option, and the first to advocate more aggressive therapies--both approaches have continued to play major roles in HIV treatment. "When we published the guidelines in 1996," says Volberding, "We thought we'd struck a pretty good target because we got criticized by some sides for being too aggressive, and from some for not being aggressive enough." The 1996 guidelines suggested that the majority of patients should be treated with two nucleosides and that the proteases should be used in patients with more immune diseases. In the 1997 edition, the experts had decided that relatively few if any patients should be offered only two drugs; the three-drug combination (two nucleosides, one protease) had become standard. More potent than the nucleoside analogs such as AZT, protease inhibitors block the maturation of released virions, rendering them non-infectious. "When combined with two nucleosides, protease inhibitors are able to almost, if not completely, prevent viral replication, thus preventing the selection of resistant forms," explains Volberding. As far as when field therapy should start, Volberding doesn't believe that the recommendations have changed much. "But we clearly know a lot more about the viral load than we did in 1996," he adds. "And in the current guidelines we will discuss using the ultra-sensitive viral load assays that are now increasingly available as well." The upcoming guidelines will also further investigate longer term treatment-related toxicities. Some of the recommendations remain vague however--and Volberding believes that's as it should be. There is no precise prescription on who should be treated and at what point. "There does have to be some judgment call," Volberding maintains. He suggests, for example, that the extent to which the patient commits to drug use must be considered.

The Scientist Staff

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