Antiretroviral Therapy in Patients with Suboptimal Virologic Suppression

The advances in our understanding of the pathogenesis of infection by human immunodeficiency virus type (HIV-1) during the past 3 years has led to antiretroviral therapeutic strategies capable of maximally suppressing plasma HIV-1 for prolonged periods of time, immunologic reconstitution, and clinical benefits including an overall decrease in HIV-related mortality. Despite these advances, up to half of patients who initiate therapy with an appropriate antiretroviral regimen either do not achieve or maintain a durable antiviral response. The reasons for suboptimal antiviral treatment responses are complex and include: acute and chronic drug intolerance, non-adherence, adverse drug interactions, pharmacokinetic variability, and drug resistance. Treatment strategies for individuals experiencing a significant increase in plasma levels of HIV-1 RNA have been recommended based on the concept of replacing the current antiretroviral treatment regimen with drugs previously not used and likely to be active. The limited number of such options has forced clinicians and researchers to search for alternative approaches including reexamination of the definition for treatment failure. Approaches such as strategic sequencing, treatment intensification, the recycling of multiple previously used drugs (i.e. mega-HAART), and scheduled treatment interruption have been attempted. Much of the success of these approaches has been dependent on the timing of such treatments and the use of either genotypic and phenotypic resistance testing. The questions remain as to when to make any change, when to add a drug, when to replace an entire regimen, and what to do if these approaches are unsuccessful. It is obvious to everyone managing the antiretroviral therapy in patients that with the currently available drugs, subsequent treatment following virologic rebound is more difficult than initiating therapy. Novel drug-sparing and recycling strategies, resistance testing and development of newer agents that target different stages in the viral life cycle and which are not cross-resistant with the current drugs will improve the ability to treat patients whose therapy is failing them.