title: Higher CD4+ T cell counts associated with low viral pol replication capacity among treatment-naive adults in early HIV-1 infection.
abstract: BACKGROUND
  Infection with primary drug-resistant human immunodeficiency virus type 1 (HIV-1) has been associated with higher CD4(+) T cell counts in drug-naive patients, suggesting that altered viral pol replication capacity (RC) associated with drug resistance diminishes immune injury in vivo, independent of exposure to drugs.
  
  
  METHODS
  Virus replication over a single cycle was measured by use of a viral test vector containing patient-derived HIV-1 protease and reverse transcriptase gene segments.
  
  
  RESULTS
  Among 191 recently infected patients, pol RC ranged widely, with only 6% of the variance explained by drug-resistance mutations. Patients infected with a virus with a low pol RC (</=43% of the reference virus) had significantly higher CD4(+) T cell counts at study entry, independent of drug resistance and plasma HIV-1 RNA level, and over time, both before and during combination antiretroviral therapy.
  
  
  CONCLUSIONS
  Viral pol RC may influence HIV-1 disease progression by affecting the amount and tissue distribution of viral replication. The pol RC value of 43% may represent a threshold below which HIV-1 has lowered virulence and is less able to deplete CD4(+) T cell counts.
authors.affiliation: Gladstone Institute of Virology and Immunology, University of California, San Francisco, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Barbour
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.forename: Terri
authors.initials: T
authors.lastname: Wrin
authors.forename: Mark R
authors.initials: MR
authors.lastname: Segal
authors.forename: Clarissa A
authors.initials: CA
authors.lastname: Ramstead
authors.forename: Teri J
authors.initials: TJ
authors.lastname: Liegler
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.forename: Christos J
authors.initials: CJ
authors.lastname: Petropoulos
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hellmann
authors.forename: James O
authors.initials: JO
authors.lastname: Kahn
authors.forename: Robert M
authors.initials: RM
authors.lastname: Grant
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015684:Gene Products, pol / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood; D014774:Virulence; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D015684:Gene Products, pol; D012367:RNA, Viral