Background:  The latency of HIV-1 in resting CD4⁺ T lymphocytes constitutes a major obstacle for the eradication of the virus in patients on ART. As yet, no approach to reduce this viral reservoir has proven effective.

Methods:  We treated 9 subjects on effective ART with high-dose intravenous immunoglobulin (IVIG) for 5 consecutive days. Highly purified resting memory CD4⁺ T cells were isolated and activated. Cells containing replication-competent HIV-1 were quantified. We also quantified HIV-1 RNA in plasma by an ultrasensitive test with detection limit of 2 copies/mL. 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:  Replication-competent HIV-1 was detected in resting T cells in 7 of the 9 subjects. IVIG had a profound effect on the latent HIV-1 pool which decreased by more than 68% during the study period (8 to 12 weeks) in 5 subjects when added to an effective ART. The decrease 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. SGS of the gag region showed that viral clones from plasma clustered together with virus from activated memory T cells.

Conclusions:  Our findings indicate that the latent HIV-1 reservoir became accessible by IVIG through activation of HIV-1 gene expression in latently-infected resting CD4⁺ T cells, possibly mediated by IL-7.