Sublime and Sobering News

It's no easy task to sum up this year's massive retrovirus conference, held in Boston from February 10 to 14, but here are my top five topics in the field of HIV medicine so far for 2003. (1) Treatment is getting simpler and less toxic. A new once-daily protease inhibitor called atazanavir may prove to be just as powerful as other protease inhibitors but with two major advantages. First, it seems not to increase cholesterol and triglyceride levels, and second, it has a unique resistance profile so that if you become resistant to it, you can probably still take most other protease inhibitors. TMC114 and tipranavir are second-generation protease inhibitors in early development that seem to have good antiviral activity'even in people with multiple protease inhibitor resistances. Amdoxovir is a nucleoside reverse transcriptase inhibitor with demonstrated activity against virus resistant to AZT-3TC and d4T-3TC. Alovudine is another NRTI in development (related to AZT) that may be active against resistant viruses. Coviracil is a new once-a-day NRTI with a resistance profile similar to that of 3TC but with a neat advantage'it works well against both HIV and hepatitis B. Gilead's once-daily reverse transcriptase inhibitor, Viread, continues to show terrific activity against HIV. New studies demonstrate that it works really well with other once-daily drugs, especially 3TC and Videx EC, but your doctor must lower your Videx EC dose to 250 milligrams daily if you use these together. TMC 125, Tibotec-Virco's second-generation nonnucleoside reverse transcriptase inhibitor, seems to be active in patients who have become resistant to first-generation NNRTIs, such as Viramune or Sustiva. Roche's fusion inhibitor, T-20 (Fuzeon), has been granted Food and Drug Administration marketing approval and seems to work well in people who are resistant to just about everything else on the market. Three drawbacks: You have to inject the drug under your skin twice a day, the injections can really hurt, and it is priced at over $20,000 per year. New ways to stop HIV are being identified, as are the drugs to take advantage of their viral life cycle targets: Attachment inhibitors, integrase inhibitors, RNA interference drugs, monoclonal antibodies, and gene therapy are all in active clinical development, albeit in the early stages. (2) Sex is getting riskier. Syphilis and gonorrhea rates are skyrocketing, the transmission of multidrug-resistant HIV is on the rise, new drug-resistant staph infections are exploding onto the scene, and people who may be 'supertransmitters' of HIV have been identified. All in all, a scary situation. The best idea is to reaffirm your commitment to safer sex and to reduce your number of sexual partners. (3) The longer people live with HIV, the greater the risk of suffering heart attacks. Studies show that HIV infection itself and the medications needed to treat it are associated with an increased risk of heart disease. One study of over 23,000 HIV-positive patients indicated that the risk of a heart attack over seven years increased 27% per year, every year, for people on treatment. Patients should not start abandoning their HIV treatment, though, because the overall risk of a heart attack is still low. Traditional risk factors, such as smoking, high cholesterol, a family history of heart problems, diabetes, older age, and being male, can contribute more to the risk of a heart attack than HIV therapy alone. (4) Vaccines that actually do something tangible are a long way off. AIDSVAX was dealt a crushing blow when it was demonstrated that the vaccine had virtually no effect in preventing HIV infection in 5,400 volunteers. The fundamental problem of protecting people from the different strains of the mutating virus may prove to be an obstacle to the development of a truly effective vaccine. (5) Lipodystrophy is still a mystery. We can successfully liposuction out those 'buffalo humps' and fill up people's hollowed faces with silicone injections, but we still don't know exactly what causes lipodystrophy. The best option for dealing with it is to avoid blaming a single drug or theory and instead focus on the scientific developments regarding what is really going on. This is where your doctor's expertise and cautious interpretation should come in handy. Cohan is an attending physician and managing director with Pacific Oaks Medical Group, one of the nation's largest practices devoted to HIV care, located in Beverly Hills, Calif.