title: Impact of inversion of the CD4/CD8 ratio on the natural history of HIV-1 infection.
abstract: BACKGROUND
  HIV-1 infection is characterized by an inverted CD4/CD8 T-cell ratio, but the distribution of inversions over time after seroconversion and whether delay of inversion is associated with a favorable prognosis are not known.
  
  
  METHODS
  T-cell counts and clinical outcomes among men in the Multicenter AIDS Cohort Study who had incident HIV-1 infection before December 31, 1995 were analyzed by Kaplan-Meier and Cox proportional hazards methods. Results were also analyzed by time-dependent multivariate methods to adjust for CD4 lymphocyte counts, viral loads, age, race, and polymorphisms in host chemokine receptor genes (CCR5-Delta32 and CCR2-64I).
  
  
  RESULTS
  Among 424 cases whose date of seroconversion was known to within +/-4.5 months, 317, 52, and 55 inverted their CD4/CD8 ratio within less than 1, 1 to 2, and more than 2 years of seroconversion, respectively. Longer time to inversion was significantly associated with longer time to AIDS, even after adjusting for CD4 lymphocyte count and viral load at the first seropositive visit and over the first 3 seropositive visits. Of the 6 seroconverters who had more than 500 CD4 lymphocytes 10 years after seroconversion without receiving highly active antiretroviral therapy, 5 took more than 2 years to invert their CD4/CD8 ratio.
  
  
  CONCLUSIONS
  Time from HIV-1 seroconversion to inversion of the CD4/CD8 ratio independently predicted time to AIDS. Early measurements of the CD4/CD8 ratio until inversion occurs may identify people likely to become long-term nonprogressors or slow progressors, thus facilitating detailed studies of the mechanism of HIV-1 disease progression.
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. jmargoli@jhsph.edu
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Margolick
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gange
authors.forename: Roger
authors.initials: R
authors.lastname: Detels
authors.forename: Maurice R G
authors.initials: MR
authors.lastname: O'Gorman
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
authors.forename: Shenghan
authors.initials: S
authors.lastname: Lai
mesh_terms: D000328:Adult; D016516:CD4-CD8 Ratio; D015331:Cohort Studies; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology*; D020276:HIV Long-Term Survivors; D006679:HIV Seropositivity; D015497:HIV-1; D006801:Humans; D008297:Male; D013223:Statistics as Topic; D013997:Time Factors