Reduction of the HIV-1 reservoir in resting CD4+ T-lymphocytes by high dosage intravenous immunoglobulin treatment: a proof-of-concept study
Artikel i vetenskaplig tidskrift, 2009

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.

Författare

Annica Lindkvist

Karolinska Institutet

Arvid Edén

Göteborgs universitet

Melissa M Norström

Swedish Institute for Infectious Disease Control

Karolinska universitetssjukhuset

Veronica D Gonzalez

Karolinska Institutet

Staffan Nilsson

Göteborgs universitet

Chalmers, Matematiska vetenskaper, matematisk statistik

Bo Svennerholm

Göteborgs universitet

Annika C Karlsson

Swedish Institute for Infectious Disease Control

Karolinska universitetssjukhuset

Johan K Sandberg

Karolinska Institutet

A. Sonnerborg

Karolinska Institutet

Magnus Gisslén

Göteborgs universitet

AIDS Research and Therapy

1742-6405 (ISSN)

Vol. 6 15- 15

Ämneskategorier

Mikrobiologi inom det medicinska området

DOI

10.1186/1742-6405-6-15

PubMed

19570221