Reduction of the HIV-1 reservoir in resting CD4+ T-lymphocytes by high dosage intravenous immunoglobulin treatment: A proof-of-concept study

被引：28

作者：

Lindkvist A. ^{[1
]}

Edén A. ^{[2
]}

Norström M.M. ^{[3
,4
]}

Gonzalez V.D. ^{[5
]}

Nilsson S. ^{[6
]}

Svennerholm B. ^{[7
]}

Karlsson A.C. ^{[3
,4
]}

Sandberg J.K. ^{[5
]}

Sönnerborg A. ^{[1
,8
]}

Gisslén M. ^{[2
]}

机构：

[1] Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institute, Stockholm

[2] Department of Infectious Diseases, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg

[3] The Swedish Institute for Infectious Disease Control, Solna

[4] Department of Microbiology, Tumour and Cell Biology MTC, Karolinska Institute, Stockholm

[5] Center for Infectious Medicine, Department of Medicine, Karolinska Institute, Stockholm

[6] Department of Mathematical Statistics, Chalmers University of Technology, Gothenburg

[7] Department of Clinical Virology, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg

[8] Department of Infectious Diseases, Karolinska Institute, Stockholm

来源：

AIDS Research and Therapy | / 6卷 / 1期

关键词：

Plasma Viral Load; IVIG Treatment; Peptide Pool; Latent Reservoir; High Dosage Intravenous Immunoglobulin;

D O I：

10.1186/1742-6405-6-15

中图分类号：

学科分类号：

摘要：

Background: The latency of HIV-1 in resting CD4+ T-lymphocytes constitutes a major obstacle for the eradication of virus in patients on antiretroviral therapy (ART). As yet, no approach to reduce this viral reservoir has proven effective. Methods: Nine subjects on effective ART were included in the study and treated with high dosage intravenous immunoglobulin (IVIG) for five consecutive days. Seven of those had detectable levels of replication-competent virus in the latent reservoir and were thus possible to evaluate. Highly purified resting memory CD4+ T-cells were activated and cells containing replication-competent HIV-1 were quantified. HIV-1 from plasma and activated memory CD4+ T-cells were compared with single genome sequencing (SGS) of the gag region. T-lymphocyte activation markers and serum interleukins were measured. Results: The latent HIV-1 pool decreased with in median 68% after IVIG was added to effective ART. The reservoir decreased in five, whereas no decrease was found in two subjects with detectable virus. Plasma HIV-1 RNA ≥ 2 copies/mL was detected in five of seven subjects at baseline, but in only one at follow-up after 8-12 weeks. The decrease of the latent HIV-1 pool and the residual plasma viremia was preceded by a transitory low-level increase in plasma HIV-1 RNA and serum interleukin 7 (IL-7) levels, and followed by an expansion of T regulatory cells. The magnitude of the viral increase in plasma correlated to the size of the latent HIV-1 pool and SGS of the gag region showed that viral clones from plasma clustered together with virus from activated memory T-cells, pointing to the latent reservoir as the source of HIV-1 RNA in plasma. Conclusion: The findings from this uncontrolled proof-of-concept study suggest that the reservoir became accessible by IVIG treatment through activation of HIV-1 gene expression in latently-infected resting CD4+ T-cells. We propose that IVIG should be further evaluated as an adjuvant to effective ART. © 2009 Lindkvist et al; licensee BioMed Central Ltd.

引用

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