January 27, 2003
Modeled on DOT for the treatment of TB, DAART's potential scope is limited by a number of factors. TB is generally cured by 6-12 months of treatment. HIV, on the other hand, requires lifelong treatment, which poses some practical problems for the use of DAART. TB can be dosed as infrequently as twice a week for most of the treatment interval, while HIV regimens must be administered once or twice daily. "Thus," the authors reasoned, "only modified DAART strategies, where some fraction of doses is self-administered, will be practical in most settings, with some exceptions (e.g., prisons and residential living facilities)." Furthermore, the researchers caution that while TB drug resistance is not common in most developed countries, the biology and dynamics of HIV infection promote rapid emergence of resistance. In fact, estimates hold that the majority of HIV-infected patients in the United States have some degree of antiretroviral resistance. Therefore, the authors conclude, it is difficult to predict the effects of DAART on the development of resistance.
Community-based outreach centers, prisons, long-term care facilities, substance abuse treatment sites and resource-poor countries have all been proposed for DAART. Pilot studies of community-based programs, prisons, and methadone maintenance clinics have shown DAART to be effective in unique settings that capitalize on frequent interactions between patients and health care personnel. "Before the use of DAART in resource-poor countries is embraced," the authors cautioned, "it should be proven efficacious in well-conducted randomized trials."
The authors point to studies that show self-administered doses are adhered to most often when patients' families assist with the doses. They question how long DAART should be administered, given the lifelong nature of antiretroviral treatments. They note that antiretroviral regimens that could be administered once daily (QD) would be best suited for DAART, although the FDA has currently only approved three such drugs. Amprenavir combined with ritonavir was the first QD protease inhibitor the FDA approved. Other agents are under investigation. Lucas and colleagues bring up the theoretical problem of an increased possibility of resistance should one QD dose be missed or taken late. Drug toxicity, fed/fasting requirements, geography, economics, local drug resistance profiles and patient's prior history of antiretroviral exposure all are factors influencing the selection of agents, according to the report.
AIDS Patient Care and STDs
11.02; Vol. 16; No. 11: P. 527-535; Gregory M. Lucas, M.D.; Charles W. Flexner, M.D.; Richard D. Moore, M.D., M.H.Sc.