title: Frequent detection of cell-associated HIV-1 RNA in patients with plasma viral load <50 copies/ml.
abstract: Despite prolonged undetectable plasma viral load some HIV-1 infected patients have been reported to develop resistance-associated mutations leading to treatment failure. The mechanisms for this phenomenon and the point of origin for residual viral evolution are still not elucidated. In order to quantify cell-associated HIV-1 RNA in patients with different levels of plasma viremia paired cell-associated HIV-1 RNA loads and plasma viral loads were determined. Weak inverse correlation between these parameters and the amounts of CD4(+) T cells was observed, whereas there was no correlation between viral loads and CD8(+) T cells or CD14(+) monocytes, respectively. In a subset of patients, cell-associated and plasma HIV-1 env V3 sequences were analyzed. Plasma viral load and the amount of cell-associated HIV-RNA correlated strongly. However, in 62.3% of patients with undetectable plasma viral load cell-associated HIV-RNA could be detected. Analyses of HIV-RNA in plasma and blood cells showed identical sequences in 4/19 patients, whereas the majority of patients had differing HIV-1 RNA sequences in plasma and cells, respectively. In summary, this study shows that residual viral replication in peripheral blood still occurs in the majority of patients with undetectable plasma viral load. Since these replication events could lead to ongoing viral evolution it should be considered to optimize antiretroviral therapy in order to minimize the development of drug resistance.
authors: Institute of Medical Microbiology, Immunology, and Parasitology, University of Bonn, Bonn, Germany.
authors: Bernd
authors: B
authors: Kupfer
authors: Bertfried
authors: B
authors: Matz
authors: Martin P
authors: MP
authors: Däumer
authors: Fabienne
authors: F
authors: Roden
authors: Jürgen K
authors: JK
authors: Rockstroh
authors: Nazifa
authors: N
authors: Qurishi
authors: Ulrich
authors: U
authors: Spengler
authors: Rolf
authors: R
authors: Kaiser
mesh_terms: D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D003430:Cross-Sectional Studies; D005814:Genes, Viral; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008214:Lymphocytes / Q000276:immunology / Q000821:virology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis; D016415:Sequence Alignment; D019562:Viral Load
chemical_list: D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D018950:Lipopolysaccharide Receptors; D010446:Peptide Fragments; D012367:RNA, Viral