Frequent detection of cell-associated HIV-1 RNA in patients with plasma viral load <50 copies/ml

• Published in: Journal of medical virology Vol. 79; no. 10; pp. 1440 - 1445
• Main Authors: Kupfer, Bernd, Matz, Bertfried, Däumer, Martin P, Roden, Fabienne, Rockstroh, Jürgen K, Qurishi, Nazifa, Spengler, Ulrich, Kaiser, Rolf
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.10.2007; Wiley-Liss
• Subjects: Amino Acid Sequence; Biological and medical sciences; CD4+ T lymphocytes; CD4-Positive T-Lymphocytes - virology; CD8-Positive T-Lymphocytes - virology; Cross-Sectional Studies; Fundamental and applied biological sciences. Psychology; Genes, Viral; HIV Envelope Protein gp120 - genetics; HIV Infections - virology; HIV-1 - genetics; HIV-1 - isolation & purification; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious diseases; intracellular; Lipopolysaccharide Receptors - biosynthesis; Lymphocytes - immunology; Lymphocytes - virology; Medical sciences; Microbiology; Miscellaneous; Molecular Sequence Data; PBMC; Peptide Fragments - genetics; residual replication; RNA, Viral - analysis; Sequence Alignment; sequence analysis; transcription; Viral diseases; Viral Load; Virology; Human; residual replication; Biological fluid; Transcription; HIV-1 virus; Retroviridae; CD4+ T lymphocytes; Lentivirus; In vitro; PBMC; Blood plasma; Virus; T-Lymphocyte; Replication; sequence analysis; Human immunodeficiency virus; Intracellular; Detection; Viral load
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.20993

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. J. Med. Virol. 79:1440-1445, 2007. © Wiley-Liss, Inc.