title: Lack of evidence for changing virulence of HIV-1 in North America.
abstract: BACKGROUND
  Several long-term cohort studies and in-vitro fitness assays have resulted in inconsistent reports on changes in HIV-1 virulence, including reports of decreasing, stable, and increasing virulence over the course of the AIDS pandemic. We tested the hypothesis of changing HIV-1 virulence by examining trends in prognostic clinical markers of disease progression from 1984 to 2005 among nearly 400 antiretroviral-naïve participants in the United States Multicenter AIDS Cohort Study (MACS), a longitudinal study of HIV infection in men who have sex with men (MSM).
  
  
  RESULTS
  Because clinical AIDS endpoints could not be used (due to antiretroviral therapies and prophylaxis), three prognostic markers of disease progression were used as proxies for HIV-1 virulence: plasma viral RNA load and CD4+ T cell count at "set point" (between approximately 9 and approximately 15 months after seroconversion), and rate of CD4 cell decline within three years after seroconversion. We performed multivariate analyses of the association between these markers and seroconversion year, with covariates including MACS site, race/ethnic group, seroconversion age, and CCR5Delta32 status. No statistically significant association was found between year of seroconversion and "set point" plasma viral load (at approximately 9 months after seroconversion: slope = -0.004 log(10) copies/mL/year, p = 0.76; at approximately 15 months: slope = -0.005 log(10) copies/mL/year, p = 0.71), CD4 cell count after seroconversion (at approximately 9 months: slope = -0.112 cells/microL/year, p = 0.22; at approximately 15 months: slope = -0.047 cells/microL/year, p = 0.64), or rate of CD4 cell decline over the first three years after seroconversion (slope = -0.010 cells/ul/yr(2), p = 0.88).
  
  
  CONCLUSIONS
  The lack of significant trends from 1984 to 2005 in these prognostic markers of HIV disease progression suggests no major change in HIV-1 virulence over the AIDS pandemic in MSM in the US.
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Herbeck
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Gottlieb
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Li
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hu
authors.forename: Roger
authors.initials: R
authors.lastname: Detels
authors.forename: John
authors.initials: J
authors.lastname: Phair
authors.forename: Charles
authors.initials: C
authors.lastname: Rinaldo
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Margolick
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D018450:Disease Progression; D015658:HIV Infections / Q000453:epidemiology; D006679:HIV Seropositivity; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009656:North America; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D014481:United States; D019562:Viral Load / Q000639:trends*; D014774:Virulence
chemical_list: D015415:Biomarkers; D012367:RNA, Viral