title: HLA-Bw4 identifies a population of HIV-infected patients with an increased capacity to control viral replication after structured treatment interruption.
abstract: OBJECTIVE
  After structured treatment interruption (STI) of treatment for HIV-1, a fraction of patients maintain suppressed viral loads. Prospective identification of such patients might improve HIV-1 treatment, if selected patients are offered STI.
  
  
  METHODS
  We analysed the effect of previously identified genetic modulators of HIV-1 disease progression on patients' ability to suppress viral replication after STI. Polymorphisms in the genes killer cell immunoglobulin-like receptor 3DLI (KIR3DL1)/KIR3DS1, human leucocyte antigen B (HLA-B) and HLA Complex P5 (HCP5), and a polymorphism affecting HLA-C surface expression were analysed in 130 Swiss HIV Cohort Study patients undergoing STI. Genotypes were correlated with viral load levels after STI.
  
  
  RESULTS
  We observed a statistically significant reduction in viral load after STI in carriers of HLA-B alleles containing either the Bw480Thr or the Bw480Ile epitope (mean adjusted effect on post-STI viral load: -0.82 log HIV-1 RNA copies/ml, P < 0.001; and -1.12 log copies/ml, P < 0.001, respectively). No significant effects were detected for the other polymorphisms analysed. The likelihood of being able to control HIV-1 replication using a prespecified cut-off (viral load increase < 1000 copies/ml) increased from 39% in Bw4-negative patients to 53% in patients carrying Bw4-80Thr, and to 65% in patients carrying Bw4-80Ile (P = 0.02).
  
  
  CONCLUSIONS
  These data establish a significant impact of HLA-Bw4 on the control of viral replication after STI.
authors.affiliation: Immunotherapy Laboratory, Department of Biomedicine, Outpatient Clinic, University Hospital Basel, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Stern
authors.forename: K
authors.initials: K
authors.lastname: Czaja
authors.forename: A
authors.initials: A
authors.lastname: Rauch
authors.forename: M
authors.initials: M
authors.lastname: Rickenbach
authors.forename: H F
authors.initials: HF
authors.lastname: Günthard
authors.forename: M
authors.initials: M
authors.lastname: Battegay
authors.forename: J
authors.initials: J
authors.lastname: Fellay
authors.forename: B
authors.initials: B
authors.lastname: Hirschel
authors.forename: C
authors.initials: C
authors.lastname: Hess
mesh_terms: D000328:Adult; D000368:Aged; D018450:Disease Progression; D005260:Female; D006679:HIV Seropositivity / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D006801:Humans; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D054341:Receptors, KIR3DL1 / Q000235:genetics / Q000276:immunology*; D013557:Switzerland / Q000453:epidemiology; D019562:Viral Load / Q000276:immunology*; D014779:Virus Replication / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C515083:KIR3DL1 protein, human; D054341:Receptors, KIR3DL1