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Directly Administered Antiretroviral Therapy in the Treatment of HIV Infection: Benefit or Burden?

January 27, 2003


This article is part of The Body PRO's archive. Because it contains information that may no longer be accurate, this article should only be considered a historical document.

Although combination antiretroviral treatment has a profound impact on the morbidity and mortality of HIV infection, adherence to such regimens is demanding and difficult. Inadequate adherence to medication is presumed to be a leading factor in virologic failure. In the past year, clinicians have focused attention on directly administered antiretroviral therapy (DAART) as a strategy to improve adherence and clinical outcomes. The current review provides an update on DAART use and the challenges the strategy imposes, examining settings for DAART, the role of treatment regimens with improved pharmacokinetic features, and proposing future directions for DAART.

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.

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In the future, the increased availability of QD agents and regimens could increase the potential settings in which DAART can be effective, according to the study, and such availability may also improve adherence in patients whose regimens are self-administered. "In future studies," the authors conclude, "it will be important to compare DAART with self-administered therapy in terms of initial virologic and immunologic responses, durability of responses, the development of antiretroviral resistance, and cost effectiveness."

Back to other CDC news for January 27, 2003

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Adapted from:
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.




This article was provided by CDC National Prevention Information Network. It is a part of the publication CDC HIV/Hepatitis/STD/TB Prevention News Update.
 

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