Intensification and stimulation therapy for human immunodeficiency virus type 1 reservoirs in infected persons receiving virally suppressive highly active antiretroviral therapy

Highly active antiretroviral therapy (HAART) has led to significant changes in mortalityand morbidity in the human immunodeficiency virus type 1 (HIV-1) epidemic. Nevertheless,because of molecular mechanisms of viral persistence, HAART does not eradicate HIV-1.Didanosine and hydroxyurea were added to the antiretroviral regimens of 3 HIV-1–infectedmen who were receiving stable HAART and who had HIV-1 RNA levels !50 copies/mL atthe initiation of the study protocol, as a novel intensification to attack cryptic viral replication;low-dose OKT3 was then administered, followed by a course of interleukin-2, to stimulatelatent provirus. Replication-competent virus was undetectable after treatment, and plasmaviral RNA was either undetectable or !5 copies/mL. In trial periods during which no antiretroviraltherapy was administered, the patients developed plasma viral rebound. This translationalapproach combines novel intensification and stimulation therapy to deplete residualHIV-1 reservoirs. Additional experimental approaches must be developed if HIV-1 eradicationis to become possible in patients receiving virally suppressive HAART.