Adherence, compliance, and HAART.

Abstract

Stunning advances in HIV clinical care have occurred in the past year. They represent a culmination of new understanding of HIV dynamics and pathogenesis, the development and widespread use of quantitative HIV RNA testing, and the dramatically increased efficacy of new antiretroviral agents used in combination. However, the laboratory and clinical trials environment is far different from the more diverse and complicated world of clinical practice. Here, these advances present patients and HIV care providers with significant additional challenges. Foremost among these is the translation of efficacy results obtained in clinical trials (designed to demonstrate "the best case scenario" for new therapies) into effectiveness in the usual clinical settings. There are many reasons to expect that results in practice will not directly parallel those seen in trials. Key to the success of the new highly active antiretroviral treatments (HAART) are the ability and willingness of HIV-positive individuals to adhere to complex antiretroviral regimens. (Although the term compliance is commonly used, adherence is preferable and more accurate because it implies and recognizes patient choice in therapeutics.) The goal of HAART is profound and durable suppression of viral replication. New insights into mechanisms of resistance to antiretrovirals suggest that the continuance of HIV replication in the presence of antimicrobial pressure invariably causes selection of resistant mutants and replacement of wild-type by resistant virus. Both less-active regimens and inadequate adherence to highly active regimens allow HIV to continue to replicate, creating selective pressure that increases the likelihood of resistance mutations. Full therapeutic benefit may require near-perfect adherence to the dosage, frequency, timing, and food requirements of many agents. Thus, imperfect adherence may be HAART's Achilles' heel. The primary care clinician's skill in helping patients manage and adhere to prescribed regimens may be both life preserving for the individual and of major public health …