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Reduction of the HI...
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Lindkvist, AnnicaKarolinska Institutet
(författare)
Reduction of the HIV-1 reservoir in resting CD4+ T-lymphocytes by high dosage intravenous immunoglobulin treatment: a proof-of-concept study
- Artikel/kapitelEngelska2009
Förlag, utgivningsår, omfång ...
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2009-07-01
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Springer Science and Business Media LLC,2009
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:gup.ub.gu.se/112074
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https://gup.ub.gu.se/publication/112074URI
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https://doi.org/10.1186/1742-6405-6-15DOI
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https://research.chalmers.se/publication/112074URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:219570221URI
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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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 och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Edén, Arvid,1975Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg(Swepub:gu)xedear
(författare)
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Norström, Melissa MKarolinska Institutet
(författare)
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Gonzalez, Veronica DKarolinska Institutet
(författare)
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Nilsson, Staffan,1956Gothenburg 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(Swepub:cth)staffan
(författare)
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Svennerholm, Bo,1949Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg(Swepub:gu)xsvebo
(författare)
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Karlsson, Annika CKarolinska Institutet
(författare)
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Sandberg, Johan KKarolinska Institutet
(författare)
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Sönnerborg, AndersKarolinska Institutet
(författare)
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Gisslén, Magnus,1962Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg(Swepub:gu)xgissm
(författare)
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Karolinska InstitutetInstitutionen för biomedicin, avdelningen för infektionssjukdomar
(creator_code:org_t)
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Ingår i:AIDS research and therapy: Springer Science and Business Media LLC6:11742-6405
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