title: Differences in disease progression in a cohort of long-term non-progressors after more than 16 years of HIV-1 infection.
abstract: BACKGROUND
  It is unclear whether resistance to immunologic damage in long-term non-progressors (LTNP) will last indefinitely or whether it merely represents the extreme of a Gaussian distribution, and therefore progression will occur eventually.
  
  
  METHODS
  A cohort of 19 LTNP was established in 1997. Plasma viraemia and CD4 cell counts were measured two to three times each year until 2003. Analyses of nef and vpr viral genes, CCR5 genotypes, co-receptor tropism, viral replication capacity, and immunological parameters were performed.
  
  
  RESULTS
  Twelve subjects (non-progressors, NP) showed stable CD4 cell counts over the 6-year follow-up, while seven (slow progressors, SP) showed a trend towards progressive CD4 cell depletion; however, only three SP experienced significant CD4 cell count declines. All SP had detectable plasma HIV-RNA (median 1118 copies/ml). In contrast, five of 12 NP had always undetectable viraemia. Only one patient showed a deletion in nef. The vpr R77Q change was recognized in seven patients. All patients were infected with R5 viruses. The virus replicative capacity was reduced in all tested individuals (range 5-93%). None of the patients was homozygous for the delta-32 CCR5 genotype, which was found in heterozygosis in three. CD8 T-cell activation was low in all but three individuals, all of whom had detectable viraemia and showed progressive CD4 cell depletion. Cytotoxic T lymphocyte responses were similar to those found in a control group of HIV progressors.
  
  
  CONCLUSIONS
  A substantial proportion of LTNP show low-level virus replication and progressive loss of CD4 T cells over time. Progressive immunologic damage seems to be directly associated with some degree of virus replication and T-cell activation.
authors.affiliation: Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
authors.forename: Berta
authors.initials: B
authors.lastname: Rodés
authors.forename: Carlos
authors.initials: C
authors.lastname: Toro
authors.forename: Ellen
authors.initials: E
authors.lastname: Paxinos
authors.forename: Eva
authors.initials: E
authors.lastname: Poveda
authors.forename: Manuel
authors.initials: M
authors.lastname: Martinez-Padial
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Benito
authors.forename: Victoria
authors.initials: V
authors.lastname: Jimenez
authors.forename: Terri
authors.initials: T
authors.lastname: Wrin
authors.forename: Sylvina
authors.initials: S
authors.lastname: Bassani
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
mesh_terms: D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D015331:Cohort Studies; D018450:Disease Progression; D005500:Follow-Up Studies; D015754:Genes, nef / Q000235:genetics; D016334:Genes, vpr / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D020276:HIV Long-Term Survivors; D015497:HIV-1; D006801:Humans; D008213:Lymphocyte Activation; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019562:Viral Load; D014766:Viremia / Q000276:immunology; D014779:Virus Replication