Background:  ART has transformed HIV-1 disease in resource-rich countries. We have more than 20 different antiretroviral medications or combination formulations, and in clinical trials 75% or more of antiretroviral-naïve patients achieve suppression of HIV replication to below the limits of detection of standard assays for 96 weeks or longer. However, limitations of our therapies do exist. Despite successful therapy in a substantial proportion of patients who are in care, the number of new infections in the US has not declined. Therapy for acute or early infection may benefit the individual and also have public health benefits, but any benefit to therapy of acute and early infection has been difficult to demonstrate.

Conslusions:  Multiple successful first line therapies have been studied, but currently all Department of Health and Human Services (DHHS) -recommended first line choices include a single nucleoside combination. Very long-term toxicity of our initial regimens is poorly understood and we need alternative initial therapies that are well studied if only for a minority of patients. Evidence-based data on the optimal second line treatment are also lacking. Virologic control without limited immune reconstitution remains a vexing problem for a small but real patient population. Strategies to enhance immune reconstitution as measured by CD4 increases have been uniformly unsuccessful. Finally development of novel therapies for patients with highly drug-resistant virus (which fortunately is currently uncommon) has stalled and innovate therapies for difficult to treat populations are needed.