%0 Journal Article
%T Reduction of the HIV-1 reservoir in resting CD4+ T-lymphocytes by high dosage intravenous immunoglobulin treatment: a proof-of-concept study
%A Annica Lindkvist
%A Arvid Ed¨¦n
%A Melissa M Norstr£¿m
%A Veronica D Gonzalez
%A Staffan Nilsson
%A Bo Svennerholm
%A Annika C Karlsson
%A Johan K Sandberg
%A Anders S£¿nnerborg
%A Magnus Gissl¨¦n
%J AIDS Research and Therapy
%D 2009
%I BioMed Central
%R 10.1186/1742-6405-6-15
%X 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.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 ¡İ 2 copies/mL was detected in five of seven subjects at baseline, but in only one at follow-up after 8¨C12 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.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.Although antiretroviral treatment (ART) has substantially improved the prognosis for HIV-infected patients, it does not cure the infection. Replication-competent HIV-1 persists in a stable, latent reservoir, primarily in resting CD4+ T-lymphocytes [1,2]. This reservoir enables lo
%U http://www.aidsrestherapy.com/content/6/1/15