Role of sequencing in therapy selection

The goals of sequencing antiretroviral agents are to preserve as many treatment options as possible, minimize drug toxicity, and prolong suppression of HIV. There are numerous options for sequencing antiretroviral agents when treatment fails. The most common reasons for treatment failure are the emergence of resistance and poor adherence. Data indicate that protease inhibitor therapy enhanced by ritonavir may delay the development of resistance longer than nonboosted protease inhibitor therapy. The results of using efavirenz or abacavir to simplify protease inhibitor treatment regimens for HIV-suppressed patients are promising. Although resistance to nonnucleoside reverse transcriptase inhibitors is a serious problem, sequencing them after zidovudine or abacavir therapy may be effective because of the hypersusceptibility to nonnucleoside reverse transcriptase inhibitors exhibited by viral populations in many nucleoside reverse transcriptase inhibitor-experienced patients. New antiretrovirals with greater tolerability, higher genetic barriers, and less cross-resistance than existing agents are needed to achieve further dramatic advances in treating HIV infection.