Integrase Inhibitors and Cellular Immunity Suppress Retroviral Replication in Rhesus Macaques-Reference-Cited by-同舟云学术

Integrase Inhibitors and Cellular Immunity Suppress Retroviral Replication in Rhesus Macaques

Published:2004-07-23 Issue:5683 Volume:305 Page:528-532
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Hazuda Daria J.¹²³⁴⁵,Young Steven D.¹²³⁴⁵,Guare James P.¹²³⁴⁵,Anthony Neville J.¹²³⁴⁵,Gomez Robert P.¹²³⁴⁵,Wai John S.¹²³⁴⁵,Vacca Joseph P.¹²³⁴⁵,Handt Larry¹²³⁴⁵,Motzel Sherri L.¹²³⁴⁵,Klein Hilton J.¹²³⁴⁵,Dornadula Geethanjali¹²³⁴⁵,Danovich Robert M.¹²³⁴⁵,Witmer Marc V.¹²³⁴⁵,Wilson Keith A. A.¹²³⁴⁵,Tussey Lynda¹²³⁴⁵,Schleif William A.¹²³⁴⁵,Gabryelski Lori S.¹²³⁴⁵,Jin Lixia¹²³⁴⁵,Miller Michael D.¹²³⁴⁵,Casimiro Danilo R.¹²³⁴⁵,Emini Emilio A.¹²³⁴⁵,Shiver John W.¹²³⁴⁵

Affiliation:

1. Department of Biological Chemistry, Merck Research Laboratories, Post Office Box 4, West Point, PA 19486, USA.

2. Department of Medicinal Chemistry, Merck Research Laboratories, Post Office Box 4, West Point, PA 19486, USA.

3. Department of Laboratory Animal Research, Merck Research Laboratories, Post Office Box 4, West Point, PA 19486, USA.

4. Department of Vaccine Research, Merck Research Laboratories, Post Office Box 4, West Point, PA 19486, USA.

5. Drug Metabolism and Pharmaceutical Research, Merck Research Laboratories, Post Office Box 4, West Point, PA 19486, USA.

Abstract

We describe the efficacy of L-870812, an inhibitor of HIV-1 and SIV integrase, in rhesus macaques infected with the simian-human immunodeficiency virus (SHIV) 89.6P. When initiated before CD4 cell depletion, L-870812 therapy mediated a sustained suppression of viremia, preserving CD4 levels and permitting the induction of virus-specific cellular immunity. L-870812 was also active in chronic infection; however, the magnitude and durability of the effect varied in conjunction with the pretreatment immune response and viral load. These studies demonstrate integrase inhibitor activity in vivo and suggest that cellular immunity facilitates chemotherapeutic efficacy in retroviral infections.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference20 articles.

1. Antiretroviral-Drug Resistance among Patients Recently Infected with HIV

2. Declining Morbidity and Mortality among Patients with Advanced Human Immunodeficiency Virus Infection

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