Intensification and Stimulation Therapy for Human Immunodeficiency Virus Type 1 Reservoirs in Infected Persons Receiving Virally Suppressive Highly Active Antiretroviral Therapy

Kulkosky, Joseph; Nunnari, Giuseppe; Otero, Miguel; Calarota, Sandra; Dornadula, Geetha; Hui Zhang; Malin, Anne; Sullivan, Julie; Yan Xu; DeSimone, Joseph; Babinchak, Timothy; Stern, John; Cavert, Winston; Haase, Ashley; Pomerantz, Roger J.
November 2002
Journal of Infectious Diseases;11/15/2002, Vol. 186 Issue 10, p1403
Academic Journal
Highly active antiretroviral therapy (HAART) has led to significant changes in mortality and 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-infected men who were receiving stable HAART and who had HIV-1 RNA levels <50 copies/mL at the 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 stimulate latent provirus. Replication-competent virus was undetectable after treatment, and plasma viral RNA was either undetectable or <5 copies/mL. In trial periods during which no antiretroviral therapy was administered, the patients developed plasma viral rebound. This translational approach combines novel intensification and stimulation therapy to deplete residual HIV-1 reservoirs. Additional experimental approaches must be developed if HIV-1 eradication is to become possible in patients receiving virally suppressive HAART.


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