title: Residual viraemia in HIV-1-infected patients with plasma viral load <or=20 copies/ml is associated with increased blood levels of soluble immune activation markers.
abstract: Despite undetectable viral load in conventional assays, probably all human immunodeficiency virus (HIV)-1 infected patients have residual viraemia (RV) detectable by ultra-sensitive assays. To study this issue, this study investigated virologic and immunologic consequences of RV in highly active antiretroviral therapy (HAART)-treated HIV-1-infected patients with plasma HIV-1 RNA <or=20 copies/ml. The study included 32 HAART-treated HIV-1-infected patients with HIV-1 RNA <or=20 copies/ml followed prospectively 6-monthly for 24 months. RV was detected by transcription-mediated amplification (TMA-RV) technique (Procleix HIV-1 Discriminatory Assay; Chiron) and by PCR (PCR-RV, Amplicor HIV-1 Monitor Assay; Roche Diagnostics). The association between RV and proviral-HIV-1-DNA, CD4-count, CD8-count, soluble [soluble tumour necrosis factor receptor (TNFr)-II, beta(2)-microglobulin, immunoglobulins] and cellular (HLA-DR, CD38, CD45RO, CD45RA, CD62L) T-cell markers of immune activation was investigated. In the 24-months study-period, 23 patients had >or=1 episode with TMA-RV whereas 9 patients had undetectable TMA-RV throughout the study-period. Time-points with TMA-RV and PCR-RV were associated with higher circulating sTNFrII (+0.234 ng/ml, P = 0.030) and beta(2)-microglobulin (+22 nmol/l, P = 0.016) and time-points with PCR-RV were also associated with higher IgA (+0.82 micromol/l, P = 0.035) and CD8-count (+1.18-fold, P = 0.001). Patients with TMA-RV in the study-period had higher HIV-1 RNA pre-HAART (P = 0.032). RV was not associated with proviral-HIV-1-DNA, CD4-count, CD4+HLA-DR+, CD8+HLA-DR+CD38+, CD4+CD45RA-CD45RO+, CD8+CD45RA-CD45RO+, CD4+CD45RA+CD62L+, CD8+CD45RA+CD62L+ T cells, IgG or IgM. In conclusion, RV was associated with increased blood levels of soluble immune activation markers in HAART-treated HIV-1-infected patients. The finding that RV was associated with higher pre-HAART plasma viral load suggests that RV is linked to pre-HAART disease progression.
authors.affiliation: Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark. sro@dadlnet.dk
authors.forename: S R
authors.initials: SR
authors.lastname: Ostrowski
authors.forename: T L
authors.initials: TL
authors.lastname: Katzenstein
authors.forename: B K
authors.initials: BK
authors.lastname: Pedersen
authors.forename: J
authors.initials: J
authors.lastname: Gerstoft
authors.forename: H
authors.initials: H
authors.lastname: Ullum
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D019380:Anti-HIV Agents; D007136:Immunoglobulins; D012367:RNA, Viral; D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human; D001613:beta 2-Microglobulin