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Reduction of the HI...
Reduction of the HIV-1 reservoir in resting CD4+ T-lymphocytes by high dosage intravenous immunoglobulin treatment: a proof-of-concept study
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- Lindkvist, Annica (författare)
- Karolinska Institutet
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- Edén, Arvid, 1975 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg
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- Norström, Melissa M (författare)
- Karolinska Institutet
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- Gonzalez, Veronica D (författare)
- Karolinska Institutet
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- Nilsson, Staffan, 1956 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper, matematisk statistik,Department of Mathematical Sciences, Mathematical Statistics,University of Gothenburg,Chalmers tekniska högskola,Chalmers University of Technology
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- Svennerholm, Bo, 1949 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg
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- Karlsson, Annika C (författare)
- Karolinska Institutet
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- Sandberg, Johan K (författare)
- Karolinska Institutet
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- Sönnerborg, Anders (författare)
- Karolinska Institutet
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- Gisslén, Magnus, 1962 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg
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(creator_code:org_t)
- 2009-07-01
- 2009
- Engelska.
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Ingår i: AIDS research and therapy. - : Springer Science and Business Media LLC. - 1742-6405. ; 6:1
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Abstract
Ämnesord
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- 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 >or= 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
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- ref (ämneskategori)
- art (ämneskategori)
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Lindkvist, Annic ...
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Edén, Arvid, 197 ...
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Norström, Meliss ...
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Gonzalez, Veroni ...
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Nilsson, Staffan ...
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Svennerholm, Bo, ...
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Karlsson, Annika ...
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Sandberg, Johan ...
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Sönnerborg, Ande ...
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Gisslén, Magnus, ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Mikrobiologi ino ...
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AIDS research an ...
- Av lärosätet
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Göteborgs universitet
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Chalmers tekniska högskola
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Karolinska Institutet