title: HIV replication capacity is an independent predictor of disease progression in persons with untreated chronic HIV infection.
abstract: OBJECTIVE
  To assess the effect of pol replication capacity (RC) on the hazard ratio of progression to a composite endpoint of time to progression to <350 CD4+ cells per microliter, initiation of therapy, or death.
  
  
  METHODS
  pol RC assays were performed after study closure in baseline samples obtained from 316 enrollees in a prospectively monitored cohort of treatment-naive adults with >or=450 CD4+ cells per microliter and >or=1000 HIV-1 RNA copies per milliliter.
  
  
  RESULTS
  The median RC was 79%. Patients with a lower RC had a lower median viral load (4.0 vs 4.2 Log HIV-1 RNA copies/mL, P = 0.026) and a lower rate of protease inhibitor resistance 2% vs 8%, P = 0.03). Otherwise, baseline demographic and laboratory characteristics were similar. The hazard ratio of progression to the composite endpoint was 0.73 (P = 0.041) for persons with lower RC, 2.07 per 1.0 log10 higher viral load (P < 0.001), and 0.86 per 50 cells per microliter higher CD4+ cell count (P < 0.001). The effect of lower RC was also significant in a separate analysis of time to initiation of therapy (P = 0.04).
  
  
  CONCLUSIONS
  These results show that untreated patients with lower vs higher RC had a slower rate of progression as assessed by a composite outcome of time to CD4+ count <or=350 cells per microliter, treatment initiation, or death.
authors.affiliation: Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System and David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. matthew.goetz@va.gov
authors.forename: Matthew Bidwell
authors.initials: MB
authors.lastname: Goetz
authors.forename: Robert
authors.initials: R
authors.lastname: Leduc
authors.forename: Nicole
authors.initials: N
authors.lastname: Wyman
authors.forename: Jay R
authors.initials: JR
authors.lastname: Kostman
authors.forename: Ann M
authors.initials: AM
authors.lastname: Labriola
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Lie
authors.forename: Jodi
authors.initials: J
authors.lastname: Weidler
authors.forename: Eoin
authors.initials: E
authors.lastname: Coakley
authors.forename: Michael
authors.initials: M
authors.lastname: Bates
authors.forename: Roberta
authors.initials: R
authors.lastname: Luskin-Hawk
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000201:enzymology* / Q000502:physiology*; D006801:Humans; D008297:Male; D014779:Virus Replication; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D054302:pol Gene Products, Human Immunodeficiency Virus