Pharmaceutical Update

The Food and Drug Administration approved the combined use of the protease inhibitors Invirase and Norvir on January 6. Norvir boosts the effectiveness of Invirase, which was previously approved by the FDA but is rarely used in HIV treatment alone because it does not reach optimum levels in the bloodstream. Roche and Trimeris have filed for full FDA approval of fusion inhibitor Fuzeon. Two studies have shown the drug to be safe and effective in reducing viral loads. Uni-Gold Recombigen rapid HIV test, developed by Irish firm Trinity Biotech, was cleared for marketing in December by the FDA. The test can provide results in 10 minutes from blood serum, plasma, and whole blood. Roche and Trimeris have halted the development of T-1249, a second-generation version of the fusion inhibitor Fuzeon, because of difficulties in manufacturing the medication. Basic research into an easier-to-make version of the drug will continue, and volunteers enrolled in a human trial of T-1249 will continue to receive the drug through the trial's 96-week end point. The protease inhibitor Reyataz has been shown to be significantly less likely to boost LDL cholesterol and triglyceride levels than other protease inhibitors. Researchers in Spain have reported that the protease inhibitor Kaletra is highly effective for treatment-naive patients with advanced HIV. A study of boosting protease inhibitor effectiveness by adding Norvir to a drug regimen has shown the approach produces a successful response in more than 40% of heavily treated patients with previous medication failures. Monotherapy with Emtriva, a nucleoside analog, is four- to 10-fold more effective than Epivir in reducing HIV viral levels in vitro, according to researchers in North Carolina. U.S. researchers report that prior use of Viramune for less than four weeks does not increase the risk of drug failure for patients switched to Sustiva. Both are nonnucleoside reverse transcriptase inhibitors. A 48-week study reported in the January 15 edition of Clinical Infectious Diseases shows that switching patients from anti-HIV regimens containing Zerit to those containing either Ziagen or Retrovir results in significant improvements in lipoatrophy. Researchers in Germany, evaluating the effects of nonnucleoside analogs on the central nervous system, have reported no significant difference in the number of patients who stopped taking Sustiva and those stopping Viramune due to neuropsychiatric complaints. Canadian researchers report that for HIV-positive adults with mycobacterium avium complex lung disease, a rifamycin-sparing regimen containing clofazimine is an acceptable alternative to rifamycin therapy. Cases of severe kidney toxicity, including Fanconi syndrome, led French researchers in November to issue a warning about anti-HIV regimens containing protease inhibitors (particularly Norvir and Kaletra) as well as nucleotide reverse transcriptase inhibitor Viread. They recommend that patients on regimens containing the drugs be monitored for kidney impairment. Researchers in the Netherlands report that patients who have suppressed viral levels through antiretroviral treatment have a high failure rate when switched to a drug combination containing Ziagen, Epivir, and Viread. A study by U.K. researchers shows that Norvir offers no advantages over other protease inhibitors in preventing the development of Kaposi's sarcoma. The National Institutes of Health, the Bill and Melinda Gates Foundation, and the Centers for Disease Control and Prevention have announced funding of three separate human trials of Viread as preexposure HIV prophylaxis. The drug will be studied in the United States, Cambodia, and four African nations. Gilead Sciences filed an investigational drug application in January with the FDA to develop GS 9005, a once-daily protease inhibitor with a unique drug resistance profile. TMC 125, a second-generation nonnucleoside analog, was shown in a small substudy of a Phase II clinical trial to have rapid antiviral activity in patients resistant to other NNRTI medications. A study by U.S. and Japanese researchers has shown that the experimental nonpeptidic protease inhibitor TMC 114 is effective against HIV resistant to protease inhibitors. The drug is in Phase II clinical trials. Researchers in the United States, Australia, and the Netherlands are studying the experimental drug zicontide, a synthetic form of sea snail venom, as a way to ease pain in AIDS and cancer patients who get no benefits from conventional painkillers. The Aaron Diamond AIDS Research Center, Rockefeller University, and the International AIDS Vaccine Initiative have begun a human trial of the ADVAX preventive vaccine. A 650-person study by researchers in Thailand shows that the experimental oral therapeutic HIV vaccine V-1 Immunitor boosts CD4-cell counts, lowers viral loads, and increases weight gain.