title: Effects of plasma HIV RNA, CD4+ T lymphocytes, and the chemokine receptors CCR5 and CCR2b on HIV disease progression in hemophiliacs. Hemophilia Growth and Development Study.
abstract: We have investigated the effects of plasma HIV RNA, CD4+ T lymphocytes and chemokine receptors CCR5 and CCR2b on HIV disease progression in hemophiliacs. We prospectively observed during follow-up 207 HIV-infected hemophiliacs in the Hemophilia Growth and Development Study. Plasma HIV RNA was measured on cryopreserved plasma from enrollment using the Chiron Corporation bDNA (version 2.0) assay. Genoytpe variants CCR2b-641 and CCR5-delta32 were detected using standard molecular techniques. Those with the mutant allele for CCR2b, and to a lesser extent CCR5, had lower plasma HIV RNA, and higher CD4+ T lymphocytes than did those without these genetic variants. After controlling for the effects of plasma HIV RNA and CD4+ T lymphocytes, those with the CCR2b mutant allele compared with those wild-type, had a trend toward a lower risk of progression to AIDS, adjusted relative hazard of 1.94 (95% confidence interval [CI], 0.9-4.18; p = .092), and AIDS-related death, relative hazard 1.97 (95% CI, 0.98-4.00; p = .059). We conclude that plasma HIV RNA, CD4+ T lymphocytes, and CCR genotypes are correlated, and the protective affect of CCR2b against HIV disease progression is not completely explained by plasma HIV RNA or CD4+ T-lymphocyte number.
authors.affiliation: Cedars-Sinai Burns & Allen Research Institute, Department of Medicine, and the University of California Los Angeles School of Medicine, 90048, USA. Daar@CSHS.org
authors.forename: E S
authors.initials: ES
authors.lastname: Daar
authors.forename: H
authors.initials: H
authors.lastname: Lynn
authors.forename: S
authors.initials: S
authors.lastname: Donfield
authors.forename: E
authors.initials: E
authors.lastname: Gomperts
authors.forename: M W
authors.initials: MW
authors.lastname: Hilgartner
authors.forename: K
authors.initials: K
authors.lastname: Hoots
authors.forename: D
authors.initials: D
authors.lastname: Chernoff
authors.forename: C
authors.initials: C
authors.lastname: Winkler
authors.forename: S J
authors.initials: SJ
authors.lastname: O'Brien
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D002648:Child; D015331:Cohort Studies; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification; D006467:Hemophilia A / Q000150:complications*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics; D018121:Receptors, Cytokine / Q000235:genetics
chemical_list: C515334:CCR2 protein, human; D012367:RNA, Viral; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine