title: Increased rate of CD4+ T-cell decline and faster time to antiretroviral therapy in HIV-1 subtype CRF01_AE infected seroconverters in Singapore.
abstract: BACKGROUND
  It remains controversial as to whether HIV-1 subtypes influence disease progression. Singapore offers a unique opportunity to address this issue due to the presence of co-circulating subtypes. We compared subtype CRF01_AE and non-CRF01_AE infected patients, with regards to estimated annual rate of CD4+ T-cell loss and time from estimated data of seroconversion (EDS) to antiretroviral therapy (ART).
  
  
  METHODS
  We recruited ART-naive patients with known dates of seroconversion between October 2002 and December 2007 at the Singapore Communicable Disease Centre, the national reference treatment centre. Multilevel mixed-effects models were used to analyse the rate of CD4+ T-cell decline. Time from EDS to ART was analyzed with the Kaplan-Meier survival method and compared with Cox proportional hazards models.
  
  
  RESULTS
  54 patients with previously assigned HIV-1 subtypes (24 CRF01_AE, 17 B, 8 B', 1 CRF33_01B, 3 CRF34_01B and 1 G) were observed for 89 patient-years. Subtype CRF01_AE and non-CRF01_AE infected patients did not differ in age, gender, risk factor, rate of symptomatic seroconversion, baseline CD4+ T-cell count, log(10) viral load or haemoglobin concentration. The estimated annual rate of CD4+ T-cell loss was 58 cells/mm(3)/year (95% CI: 7 to 109; P = 0.027) greater in subtype CRF01_AE infected patients compared to non-CRF01_AE patients, after adjusting for age, baseline CD4+ T-cell count and baseline log(10) viral load. The median time from EDS to ART was 1.8 years faster comparing CRF01_AE to non-CRF01_AE infected patient with a 2.5 times (95% CI: 1.2-5.0; P = 0.013) higher hazard for ART initiation, after controlling for age, baseline CD4+ T-cell count and baseline log(10) viral load.
  
  
  CONCLUSIONS
  Infecting subtype significantly impacted the rate of CD4+ T-cell loss and time to treatment in this cohort. Studies to understand the biological basis for this difference could further our understanding of HIV pathogenesis.
authors.affiliation: Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore Maryland, United States of America. oong@jhsph.edu
authors.forename: Oon Tek
authors.initials: OT
authors.lastname: Ng
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.forename: Yong Jiang
authors.initials: YJ
authors.lastname: Sun
authors.forename: Cheng Chuan
authors.initials: CC
authors.lastname: Lee
authors.forename: Yee Sin
authors.initials: YS
authors.lastname: Leo
mesh_terms: D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology*; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006679:HIV Seropositivity; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012846:Singapore; D013997:Time Factors; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents