title: CXCR4 or CCR5 tropism of human immunodeficiency virus type 1 isolates does not determine the immunological milieu in patients responding to antiretroviral therapy.
abstract: Here we address whether CCR5 or CXCR4 tropism of the predominant viral strain detected before or on combination antiretroviral therapy (ART) explains why some human immunodeficiency virus (HIV)-infected patients who begin ART with advanced HIV disease retain low interferon (IFN)-gamma responses, despite recovery of CD4(+) T cell counts. Tropism was determined by culture and confirmed by gp120 V3 loop sequence of multiple plasma samples in eight adult male patients who began treatment with <50 CD4(+) T cells/microL. Four patients had mixed infections, one had only R5 HIV, and three had only X4 HIV. Of these, two carried CCR5Delta32. Viral tropism was not related to CD4(+) T cell counts or HIV RNA levels. When immunological responses were monitored over several years, IFN-gamma responses to cytomegalovirus were below the median value of uninfected controls and similar in patients with R5, X4, or mixed infection. Interleukin-5 responses were low and plasma soluble CD30 levels were high at treatment onset, but resolved with control of HIV replication irrespective of HIV tropism. Levels of LAG-3 (lymphocyte activation gene-3 protein) were elevated in patients with uncontrolled HIV replication. Hence the immunological milieu did not reflect HIV tropism.
authors.affiliation: School of Surgery and Pathology, University of Western Australia, Perth, WA, Australia. pprice@cyllene.uwa.edu.au
authors.forename: Patricia
authors.initials: P
authors.lastname: Price
authors.forename: Niamh
authors.initials: N
authors.lastname: Keane
authors.forename: Lachlan
authors.initials: L
authors.lastname: Gray
authors.forename: Silvia
authors.initials: S
authors.lastname: Lee
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gorry
authors.forename: Martyn A
authors.initials: MA
authors.lastname: French
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000097:blood; D018791:CD4 Lymphocyte Count; D003587:Cytomegalovirus / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D017730:Ki-1 Antigen / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D016896:Treatment Outcome; D014779:Virus Replication; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D044966:Anti-Retroviral Agents; D015703:Antigens, CD; D015848:Interleukin-5; D017730:Ki-1 Antigen; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D007371:Interferon-gamma; D000093322:Lymphocyte Activation Gene 3 Protein