Challenges of the unmet needs in the treatment-experienced patient

Despite significant therapeutic advances in HIV medicine, virologic failures remain frequent in clinical practice. Issues such as suboptimal antiretroviral activity, poor tolerability, inconvenient dosing schedules, long-term toxicity, and low thresholds for the development of resistance all limit the clinical utility of HIV reverse transcriptase and protease inhibitors. Maintaining optimal viral suppression often necessitates that patients change treatment, but drug resistance and cross-resistance can rapidly reduce the number of effective treatments available. On the other hand, the therapeutic success achieved since the introduction of HAART has led to an increased overall exposure to antiretroviral drugs, and new toxicities have emerged. True second-generation agents and agents active against new targets will be essential to maximize the therapeutic impact of current antiretroviral therapy and minimize the risk of resistance development.