title: HIV-1 subtype B/B' and baseline drug resistance mutation are associated with virologic failure: a multicenter cohort study in China.
abstract: BACKGROUND
  Distribution of HIV-1 subtypes, transmitted drug resistance (TDR)/drug resistance mutation (DRM), and their impact on response to combination antiretroviral therapy remain poorly understood in China.
  
  
  METHODS
  We analyzed data from our multicenter cohort study with 444 antiretroviral-naive participants recruited between 2008 and 2010. HIV-1 subtype and tropism were determined by V3 sequencing, and TDR/DRM was determined by Pol sequencing. Virologic and immunologic responses were monitored over 96 weeks of follow-up. The initial combination antiretroviral therapy regimen for all patients was nevirapine + lamivudine + zidovudine or stavudine. Analysis 1 included patients who finished 96 weeks of follow-up (n = 379), and analysis 2 included all 444 patients.
  
  
  RESULTS
  Subtype B/B' was associated with higher prevalence of TDR/DRM to nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors. Median time to HIV-1 suppression was 18 weeks in all 3 subtype groups. In Cox proportional models for viral suppression, neither viral tropism nor HIV-1 subtypes had any impact on viral suppression; however, subtypes CRF01_AE and C/CRF07_BC/CRF08_BC were associated with lower risk of virologic failure compared with subtype B/B', with adjusted hazard ratio of 0.11 (P = 0.032) and 0.06 (P = 0.036), respectively in analysis 1, 0.42 (P = 0.047) and 0.22 (P = 0.008), respectively in analysis 2. This association was attenuated by adding DRM profiles to multivariate regression models. Neither subtype nor HIV-1 tropism affected immunologic response.
  
  
  CONCLUSIONS
  HIV-1 subtype tended to be associated with virologic but not immunologic response; this effect could be ascribed to baseline DRM.
authors.affiliation: *Department of Infectious Diseases, Peking Union Medical College Hospital, Beijing, China; †Research Center for Asian Infectious Diseases, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan; and ‡Japan-China Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yijia
authors.initials: Y
authors.lastname: Li
authors.forename: Lijun
authors.initials: L
authors.lastname: Gu
authors.forename: Yang
authors.initials: Y
authors.lastname: Han
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.forename: Huanling
authors.initials: H
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Lv
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Song
authors.forename: Yanling
authors.initials: Y
authors.lastname: Li
authors.forename: Aikichi
authors.initials: A
authors.lastname: Iwamoto
authors.forename: Takaomi
authors.initials: T
authors.lastname: Ishida
authors.forename: Taisheng
authors.initials: T
authors.lastname: Li
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D002681:China; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D017211:Treatment Failure; D019562:Viral Load; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D054302:pol Gene Products, Human Immunodeficiency Virus