Deep Salvage'When All Else Fails

Rates of HIV drug resistance have been rising sharply in recent years. According to a 2002 report in The New England Journal of Medicine, from 1995 to 2000 the percentage of patients who were resistant to at least one HIV medication quadrupled from 3.4% to over 12.4%. Another study, by University of California, San Diego, researcher Doug Richman, showed that of patients who were taking HIV medications for at least two years, 78% had resistance to one drug and 51% had resistance to multiple drugs. Resistance testing has become so completely integrated into our standard of care for HIV that the July 14, 2003, revised Department of Health and Human Services Guidelines for HIV Treatment stipulate that no patient or provider should consider making a drug switch from a failing regimen without doing resistance testing. Here are 10 dos and don'ts for dealing with a highly drug-resistant virus: ' Do not panic. Lots of research is going on, and many new drugs are in development to treat drug-resistant viruses. ' Do not stop your medications. If you do this, the more destructive 'wild type' virus may emerge and destroy your immune system very quickly. 'Resistant' viruses are actually not 100% resistant to the medications. The medicines may force the virus to mutate so severely that although HIV can reproduce, it cannot effectively harm your CD4 cells because it is a weaker virus. ' Do not add a single new drug to a failing regimen. Adding the latest Food and Drug Administration'approved drug to a drug-resistant regimen is doomed to failure, since three working (nonresistant) drugs are usually required to suppress your virus. ' Do not start taking lots of overhyped, unapproved 'alternative' treatments or supplements. These usually do nothing good for your immune system and can actually interfere with the effectiveness of your current antiretrovirals. They can also possibly cause liver, kidney, or other organ damage. ' Do get a resistance test. Resistance testing by a reputable laboratory can make a world of difference in picking the right drugs. Genotype tests indicate which genetic mutations your virus has developed, while phenotype tests determine how well specific anti-HIV drugs actually suppress your virus. ' Do consider the results from all previous resistance tests. Since HIV resistance mutations never really go away, you should make sure that your doctor reviews all of your previous resistance tests to guide new drug selection. Even though certain mutations may seem to disappear on a new resistance test, they probably are still lurking around in hard-to-detect quantities and might sabotage a new drug regimen if not taken into consideration. ' Do have your doctor monitor your immune status closely. Make sure that you do not go for more than 12 weeks without your doctor checking your CD4-cell count and viral load. People with HIV-resistant virus are sometimes under the impression that nothing can be done for them and stay away from medical monitoring for long periods of time. Unfortunately, doing so risks missing a major CD4-cell drop and other preventable HIV-related complications. ' Do consider intensifying your current regimen with another protease inhibitor or boosting the levels of your current drugs with small doses of ritonavir. ' Do consider trying a whole new class or generation of drugs. Try a fusion inhibitor (Fuzeon), the new nonnucleosides (capravirine or TMC-125), or the new protease inhibitors (tipranavir or TMC-114). Make sure to team these new drugs with other nonresistant drugs per your genotype results. ' Do consider waiting until three new, nonresistant antivirals are available. If your CD4-cell count is stable and your health is good, you should make no changes until you have a whole new drug regimen at your disposal'either via FDA-approved drugs or through a clinical research trial. In many cases of HIV drug resistance, patience is truly a virtue. Cohan is an attending physician and vice president with Pacific Oaks Medical Group, one of the nation's largest practices devoted to HIV care, located in Beverly Hills, Calif. He serves on the board of AIDS Project Los Angeles and has expertise in nutrition, anabolics, and exercise.