Approaching Eradication of Highly Active Antiretroviral Therapy–Persistent Human Immunodeficiency Virus Type 1 Reservoirs with Immune Activation Therapy

Highly active antiretroviral therapy (HAART) has dramatically altered the human immunodeficiency virus type 1 (HIV-1) pandemic in the developed world. Most patients treated with HAART will maintain clinically undetectable plasma virus loads with concomitant dramatic decreases in mortality and morbidity. Nevertheless, HAART does not eradicate HIV-1 infection on the basis of persistent low-level or cryptic viral replication and, of importance, latent provirus in resting CD4+ T lymphocytes. New approaches are now being developed for stimulation of "HAART-persistent" reservoirs. Immune activation therapy (IAT) has begun to be used in attempts to stimulate the HIV-1 latent reservoir. These studies and new approaches to activating latent virus in resting CD4+ T cells are reviewed and critically analyzed in the present report. Development of novel IAT may lead to long-term remission or viral eradication in the future.