Strategies for long-term success in the treatment of HIV infection

Highly active antiretroviral therapy has revolutionized the treatment of human immunodeficiency virus (HIV) infection, which can now be viewed as a chronic and manageable disease. However, HIV infection differs from other chronic diseases in that early treatment decisions can irrevocably alter the patient's response to future therapy. Despite the large number of approved antiretroviral agents, the number of sequential treatment regimens that will be effective for an individual patient is sharply limited by cross-resistance within the 3 drug classes. Because of the complexity of antiretroviral therapy, clinicians prescribing it require considerable expertise. Treatment should be deferred until the patient has been educated about the importance of strict adherence and has demonstrated willingness and motivation to begin therapy. Drug regimens should be chosen that the patient can tolerate and adhere to, and the consequences of resistance should be considered before therapy is begun. When treatment fails, the timing and choice of subsequent therapy can be critical in determining the magnitude and durability of response. Resistance testing can help guide the clinician in the choice of therapy. In patients who have been treated with numerous antiretroviral agents, it may be impossible to achieve significant viral suppression. Therapy may still be beneficial for such patients, but it should be tolerable and should not increase resistance to drugs that may become available in the near future. Drug resistance and treatment failure are not random events, but are the result of factors over which clinicians and their patients have some control. The treatment of drug-resistant patients is challenging; the best way to deal with resistance is to prevent it.