A Golden Age

For the past decade we have been struggling to create and re-create anti-HIV regimens that contain three active drugs from the same three basic drug classes: nucleoside reverse transcriptase inhibitors, nonnukes, and protease inhibitors--with a little help from fusion inhibitor T-20 (Fuzeon) once it was introduced in 2003. Over time, regimens have failed in some experienced patients, and the number of patients without any viable treatment options has increased. In addition, in parts of the country up to 15% of newly infected patients have a virus already resistant to at least one drug class. But as we begin 2008 I feel like we are entering what future historians might call the golden age of anti-HIV medications. This era actually started two years ago with the second-generation protease inhibitors, darunavir (Prezista) and tipranavir (Aptivus). Then in August a new class of drugs called coreceptor blockers arrived with the Food and Drug Administration's approval of maraviroc (Selzentry). Barely two months later, another new class called integrase inhibitors debuted with raltegravir (Isentress). If all goes according to schedule, a second-generation nonnuke will be approved early this year. And if we are lucky, drugs farther up the pipeline--maturation inhibitors, monoclonal CD4 antibodies, and second-generation nucleosides--will prove successful as well. This optimism is reflected in changes made to the most recent treatment guidelines of both the U.S. Department of Health and Human Services and the International AIDS Society-USA. Prior guidelines admitted that the goal of maximal suppression of viral loads to below 50 might not be possible in patients with broad treatment experience. But these current guidelines have a goal of viral loads below 50 in all patients, regardless of past medication exposure. Based on studies of maraviroc and raltegravir, these goals seem possible. In separate studies patients who were already three-class resistant were randomized to the study drug or placebo plus an optimized background therapy. At 24 weeks the arm with the study drug had about twice the percentage of patients with undetectable viral loads compared to placebo. And if the study drug was combined with an optimized background therapy containing two or more active drugs, 60% to 80% of patients achieved undetectable status. In other words, having several new classes of drugs to which there is no resistance should get about 70% of our currently unsalvageable patients to undetectable viral levels. However, amid all this optimism, we need to remember that we must not squander this bounty of new drugs. Resistance will surely arise if we fail to patiently wait to create a regimen with three active components for each patient. Let's celebrate where we are but not forget where we have been. Bowers is an HIV specialist and board-certified physician in family practice, and he is a senior partner with Pacific Oaks Medical Group, one of the largest U.S. practices devoted to HIV care, in Beverly Hills, Calif.