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(Journal of Leukocyte Biology. 2006;80:1118-1126.)
© 2006 by Society for Leukocyte Biology

Continued evolution of HIV-1 circulating in blood monocytes with antiretroviral therapy: genetic analysis of HIV-1 in monocytes and CD4+ T cells of patients with discontinued therapy

Nick Llewellyn^*, Rafael Zioni^*, Haiying Zhu^*, Thomas Andrus^*, Younong Xu^*, Lawrence Corey^*, and Tuofu Zhu^*,,1

^* Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington, USA; and
Program in Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

¹ Correspondence: Department of Laboratory Medicine, 960 Republican St., Seattle, WA 98109. E-mail: tzhu{at}u.washington.edu

ABSTRACT

The role of blood monocytes in HIV-1 infection is a relatively new field of interest. What happens to HIV-1 in monocytes and their relationship to CD4+ T cells before, during, and after suppressive antiretroviral therapy (ART) is largely unstudied. Here, considering that diversity is a good indicator of continued replication over time, we evaluated the effect of ART on HIV-1 in blood monocytes and CD4+ T cells by examining the diversity of HIV-1 from 4 infected patients who underwent and stopped therapy. We determined diversity and compartmentalization of HIV-1 between blood monocytes and CD4+ T cells in each patient in relationship to their ART regimens. Our data indicate that the rate of HIV-1 diversity increase in monocytes during therapy was significantly higher than in CD4+ T cells (P<0.05), suggesting that HIV-1 present in monocytes diversify more during therapy than in CD4+ T cells. Increased rates of HIV-1 compartmentalization between monocytes and CD4+ T cells while on therapy were also observed. These results suggest that ART inhibits HIV-1 replication in CD4+ T cells more than in blood monocytes and that better treatments to combat HIV-1 in monocytes/macrophages may be needed for a more complete suppression of HIV replication.

Key Words: treatment • leukocyte • diversity

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