The Dueling Guidelines

Not only was 2006 the 25th anniversary of the first description of what we now call AIDS, it was also the 10th anniversary of the introduction of triple-drug antiretroviral combinations. Also making its first appearance in 1996 was an antiretroviral treatment guideline from the International AIDS Society--USA. Since then, that guideline has been revised seven times, with the newest version published in the August 16, 2006, issue of The Journal of the American Medical Association. In October the Department of Health and Human Services Panel on Antiretroviral Guidelines published our other major HIV treatment guidebook. New antiretrovirals have become available since the last IAS guidelines in 2004--the total of approved drugs currently stands at 26--thus several new combinations have emerged. We have also learned some new fine points about using nucleoside reverse transcriptase inhibitors. There is more boosting of protease inhibitors with ritonavir. And there has been a head-to-head comparison of the two leading nonnucleoside analogs. That is not to mention all the conferences, published studies, and new data submitted to the Food and Drug Administration. When this latest IAS panel convened, it initiated a Medline search of all published trials of antiretrovirals since 2004. Of the 749 citations returned, reviewers deemed 181 to be relevant, then weighted those studies by the quality and strength of the data. From all of this, the 16 national HIV experts on the panel created their recommendations. In contrast, the HHS panel is a working group that's part of the Office of AIDS Research Advisory Council and meets monthly by teleconference to make revisions to its current guidelines based on any new data. So have they come up with the same conclusions? Basically yes--but not exactly. Both agree that the initial regimen should be two NRTIs (the 'backbone') plus either an NNRTI or a ritonavir-boosted PI (the 'anchor drug'). They also agree that many factors outside the basic science of 'which combination controls HIV best' are important and in some circumstances may override their recommendations. These would include risk of liver or kidney disease, elevated lipids, tuberculosis, the possibility of pregnancy, interactions with other drugs, ease of adherence, dosing restrictions with food, or baseline resistance, among other factors. When it comes down to specifics, the two guidelines have some differences, though more in format than in the actual medication choices. The HHS guideline ranks its recommendations as 'preferred,' 'alternative,' or 'acceptable.' Generally the alternative choice has a minor side effect or slightly less robust efficacy data than the preferred one. The 'acceptable' choice is usually considered inferior because of a potential significant side effect or less efficacy but would be appropriate in certain special cases. The IAS guideline simply lists all the acceptable first-line NRTIs, NNRTIs, and PIs with the advantages and disadvantages of each compared. But in the end there is no clear unanimity among the experts. There are multiple right choices of treatment regimens. Remember also that these are guidelines, not gospel. In fact, there is another factor that I feel is extraordinarily important in choosing a first regimen: patient preference. Perhaps a friend or partner had severe diarrhea with one drug or a life-threatening allergic reaction to another. That memory may be so strong for the patient that certain medications are simply not acceptable. When it is time to start treatment, let your doctor help you with the science, and you help him with your preferences. Bowers is board-certified in family practice and is a senior partner with Pacific Oaks Medical Group, one of the largest U.S. practices devoted to HIV care.