Dynamics of total, linear nonintegrated, and integrated HIV-1 DNA in vivo and in vitro 15th International AIDS Conference Koelsch, K. K., Liu, L., Haubrich, R., May, S., Havlir, D., Guenthard, H. F., Ignacio, C. C., Campos-Soto, P., Little, S. J., Shafer, R., Robbins, G. K., D'Aquila, R. T., Kawano, Y., Young, K., Dao, P., Spina, C. A., Richman, D. D., Wong, J. K. OXFORD UNIV PRESS INC. 2008: 411–19


In patients infected with human immunodeficiency virus type 1 (HIV-1), HIV-1 DNA persists during highly active antiretroviral treatment, reflecting long-lived cellular reservoirs of HIV-1. Recent studies report an association between HIV-1 DNA levels, disease progression, and treatment outcome. However, HIV-1 DNA exists as distinct molecular forms that are not distinguished by conventional assays.We analyzed HIV-1 RNA levels in plasma, CD4 cell counts, and levels of integrated and nonintegrated HIV-1 DNA in peripheral blood mononuclear cells (PBMCs) from patients with early or chronic infection before and during antiretroviral treatment. We also studied HIV-1 DNA decay in primary CD4 T cells infected in vitro. HIV-1 DNA was analyzed using an assay that is unaffected by the location of HIV-1 integration sites.HIV-1 RNA levels and total HIV-1 DNA levels decayed rapidly in patients during receipt of suppressive antiretroviral therapy. Ratios of total HIV-1 DNA levels to integrated HIV-1 DNA levels were high before initiation of therapy but diminished during therapy. Levels of linear nonintegrated HIV-1 DNA decayed rapidly in vitro (t (1/2) = 1- 4.8 days).Total HIV-1 DNA decays rapidly with suppression of virus replication in vivo. Clearance of HIV-1 DNA during the first 6 months of therapy reflects a disproportionate loss of nonintegrated HIV-1 DNA genomes, suggesting that levels of total HIV-1 DNA in PBMCs after prolonged virus suppression largely represent integrated HIV-1 genomes.

View details for DOI 10.1086/525283

View details for Web of Science ID 000253131600013

View details for PubMedID 18248304