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Prolonged control of replication-competent dual- tropic human immunodeficiency virus-1 following cessation of highly active antiretroviral therapy.
Maria Salgado; S Alireza Rabi; Karen A O'Connell; Robert W Buckheit; Justin R Bailey; Amina A Chaudhry; Autumn R Breaud; Mark A Marzinke; William Clarke; Joseph B Margolick; et al. (Profiled Authors: William Clarke; Joel Blankson; Joseph Margolick; Robert Siliciano)
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
BACKGROUND: While initiation of highly active antiretroviral therapy (HAART) during primary HIV-1 infection occasionally results in transient control of viral replication after treatment interruption, the vast majority of patients eventually experience a rebound in plasma viremia. RESULTS: Here we report a case of a patient who was started on HAART during symptomatic primary infection and who has subsequently maintained viral loads of < 50 copies/mL for more than nine years after the cessation of treatment. This patient had a high baseline viral load and has maintained a relatively high frequency of latently infected CD4(+) T cells. In addition, he does not have any known protective HLA alleles. Thus it is unlikely that he was destined to become a natural elite controller or suppressor. The mechanism of control of viral replication is unclear; he is infected with a CCR5/CXCR4 dual-tropic virus that is fully replication-competent in vitro. In addition, his spouse, who transmitted the virus to him, developed AIDS. The patient's CD4(+) T cells are fully susceptible to HIV-1 infection, and he has low titers of neutralizing antibodies to heterologous and autologous HIV-1 isolates. Furthermore, his CD8(+) T cells do not have potent HIV suppressive activity. CONCLUSION: This report suggests that some patients may be capable of controlling pathogenic HIV-1 isolates for extended periods of time after the cessation of HAART through a mechanism that is distinct from the potent cytotoxic T lymphocyte (CTL) mediated suppression that has been reported in many elite suppressors.
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Anding Shen; M Christine Zink; Joseph L Mankowski; Karen Chadwick; Joseph B Margolick; Lucy M Carruth; Ming Li; Janice E Clements; Robert F Siliciano
Resting CD4+ T lymphocytes but not thymocytes provide a latent viral reservoir in a simian immunodeficiency virus-Macaca nemestrina model of human immunodeficiency virus type 1-infected patients on highly active antiretroviral therapy.Journal of virology 2003;77(8):4938-49.
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