Overcoming resistance to existing therapies in HIV-infected patients: The role of new antiretroviral drugs

Resistance to available antiretroviral (ARV) agents is of increasing concern, and development of novel agents that address this problem has been identified as a major public health priority. As ARV resistance becomes more prevalent with extended use of existing agents, individuals with HIV infection resistant to all three traditional classes of ARVs, nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTls) and protease inhibitors (PIs), find themselves increasingly limited with regard to effective treatment options. The need for tolerable new drug regimens that effectively suppress viral replication while being simple to adhere to is increasingly pressing. This article reviews the epidemiology of antiretroviral drug resistance, the factors that contribute to the emergence of resistance, and presents data that support the need for early detection of resistance and maximal virologic suppression in order to delay treatment failure and reduce mortality. Healthcare providers are encouraged to optimize therapy through the use of new agents from existing drug classes, which can minimize cross-resistance, as well as agents with novel mechanisms of action, in order to realize the potential for greater viral containment and to forestall development of resistance mutations. This article evaluates several emerging therapies that are in late-stage clinical development and promise to expand treatment options for highly treatment-experienced patients with the goal of improving outcomes for HIV-infected individuals whose options for sustained antiviral efficacy are increasingly limited.