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.