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

Joseph Kulkosky, Giuseppe Nunnari, Miguel Otero, Sandra Calarota, Geetha Dornadula, Hui Zhang, Anne Malin, Julie Sullivan, Yan Xu, Joseph DeSimone, Timothy Babinchak, John Stern, Winston Cavert, Ashley Haase, Roger J. Pomerantz

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1403-1411
Number of pages9
JournalJournal of Infectious Diseases
Volume186
Issue number10
DOIs
StatePublished - Nov 15 2002

Bibliographical note

Funding Information:
Financial support: National Institutes of Health (grant AI-46289); Ortho Biotech (clinical grants); Bristol-Myers Squibb (to R.J.P.).

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