title: In vitro cytopathogenicity of the human immunodeficiency virus (HIV)-1 predicts survival in HIV-infected hemophiliacs independent from CD4 cell count.
abstract: In addition to quantification of viral load the graded cytopathogenicity of the human immunodeficiency virus may provide prognostic information for the course of HIV infection. However, the prognostic value of graded cytopathogenicity in addition to the CD4 count has not been evaluated in a large longitudinal study. Therefore a total of 216 HIV-seropositive hemophiliacs have been followed up from 1985 to 1998 (mean follow-up 70.4 +/- SD 26 months, median 72, range: 12 to 120 months). In vitro virulence was determined according to cytopathic effects on freshly isolated PBMC of healthy donors and graded from A (strongest cytopathogenic effect) to D (no cytopathic isolate effect). Survival was analyzed among patients with different virus isolates by Kaplan-Meier statistics (log rank) and factors independently associated with decreased survival were analyzed by Cox hazard regression analysis. - A virus isolate A was found in 22 (10.2%) patients, a virus isolate B was found in 21 (9.3%) patients, a virus isolate C was found in 9 (4.2%) and a virus isolate D was found in 10 (4.2%) patients. Mean survival times were 48 months (95% Confidence Interval (CI) = 36 - 60) in patients with isolate A, 72 months (CI = 36 - 108) with isolate B, 84 months (CI = 48-120) with isolate C, 72 months (60 - 96) with isolate D and 96 months (CI = 96 - 108) in patients with a negative virus culture (p < 0.001). Cox regression analysis indicated significant associations with outcome for young age (p <0.001), positive virus culture (p < 0.0001) and CD4 count (p < 0.0001) as independent predictors of survival. The presence of an isolate A revealed the strongest odds ratio (6.3, 95% CI 2.9-13.2). Our data indicate that the presence of a virus isolate A represents a strong risk factor for mortality in the course of HIV infection. Besides quantification of viral load and CD4 count, the graded cytopathogenicity may provide additional information for early and aggressive antiretroviral treatment, since the mean survival in patients with cytopathogenic virus isolates is reduced significantly.
authors.affiliation: Department of Internal Medicine, University of Bonn, Sigmund-Freud-Strasse, D-53105 Bonn, Germany.
authors.forename: J K
authors.initials: JK
authors.lastname: Rockstroh
authors.forename: R P
authors.initials: RP
authors.lastname: Woitas
authors.forename: H H
authors.initials: HH
authors.lastname: Brackmann
authors.forename: B
authors.initials: B
authors.lastname: Kupfer
authors.forename: R
authors.initials: R
authors.lastname: Kaiser
authors.forename: K E
authors.initials: KE
authors.lastname: Schneweis
authors.forename: T
authors.initials: T
authors.lastname: Sudhop
authors.forename: U
authors.initials: U
authors.lastname: Spengler
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology*; D015331:Cohort Studies; D005500:Follow-Up Studies; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D006467:Hemophilia A / Q000276:immunology* / Q000401:mortality / Q000821:virology*; D006801:Humans; D016130:Immunophenotyping; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D019562:Viral Load; D014774:Virulence
chemical_list: D019380:Anti-HIV Agents