Changes in the approach to treatment of HIV infection evolve rapidly, fueled by the approval of new antiretroviral agents (ARVs) and new information on how best to use both new and old agents. For over a decade, the International AIDS Society-USA (IAS-USA) and others have recognized the need for expert recommendations to address 4 key questions: (1) When should antiretroviral therapy be started? (2) What regimen(s) should be used for initial therapy? (3) When should therapy be changed? and (4) What should it be changed to? The IAS-USA consensus guidelines are updated as needed, with the last recommendations published in 2004. The purpose of this review is to consider the developments in antiretroviral therapy over the past 18 months and to examine how new data and new agents affect the treatment of patients with HIV infection.
While technical, the article is clear enough for the knowledgeable layperson to understand. Charts and tables augment the text. Some of the conclusions include:
- When should we start therapy? We know that there is a continuum of risk associated with viral replication and immune dysfunction. Although the optimum time for initiating therapy remains elusive, it is clear that treatment should be started before irreversible immune dysfunction occurs. As regimens improve with respect to potency and toxicity, earlier therapy will likely become the rule.
- What should we start with?Not all regimens are equal, and a few are emerging as preferable for initial therapy. Efficacy, toxicity, and long-term strategies remain key considerations in guiding the choice of initial regimens.
- When should therapy be switched?Switching regimens should be considered for virologic failure or toxicity, and toxicity monitoring should be rigorous.
- What should therapy be changed to?Drug resistance testing should be incorporated into routine clinical management, and follow-up regimens should be determined on the basis of expected potency, likelihood of adherence, and toxicity concerns. The concept of structured treatment interruptions has not been validated.