title: HIV-1 drug resistance in antiretroviral-naive individuals with HIV-1-associated tuberculous meningitis initiating antiretroviral therapy in Vietnam.
abstract: BACKGROUND
  Access to antiretroviral therapy (ART) for HIV-infected individuals in Vietnam is rapidly expanding, but there are limited data on HIV drug resistance (HIVDR) to guide ART strategies.
  
  
  METHODS
  We retrospectively conducted HIVDR testing in 220 ART-naive individuals recruited to a randomized controlled trial of immediate versus deferred ART in individuals with HIV-associated tuberculous meningitis in Ho Chi Minh City (HCMC) from 2005-2008. HIVDR mutations were identified by population sequencing of the HIV pol gene and were defined based on 2009 WHO surveillance drug resistance mutations (SDRMs).
  
  
  RESULTS
  We successfully sequenced 219/220 plasma samples of subjects prior to ART; 218 were subtype CRF01_AE and 1 was subtype B. SDRMs were identified in 14/219 (6.4%) subjects; 8/14 were resistant to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs; T69D, L74V, V75M, M184V/I and K219R), 5/14 to non-nucleoside reverse transcriptase inhibitors (NNRTIs; K103N, V106M, Y181C, Y188C and G190A), 1/14 to both NRTIs and NNRTIs (D67N and Y181C) and none to protease inhibitors. After 6 months of ART, eight subjects developed protocol-defined virological failure. HIVDR mutations were identified in 5/8 subjects. All five had mutations with high-level resistance to NNRTIs and three had mutations with high-level resistance to NRTIs. Due to a high early mortality rate (58%), the effect of pre-existing HIVDR mutations on treatment outcome could not be accurately assessed.
  
  
  CONCLUSIONS
  The prevalence of WHO SDRMs in ART-naive individuals with HIV-associated tuberculous meningitis in HCMC from 2005-2008 is 6.4%. The SDRMs identified conferred resistance to NRTIs and/or NNRTIs, reflecting the standard first-line ART regimens in Vietnam.
authors.affiliation: Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Vu P
authors.initials: VP
authors.lastname: Thao
authors.forename: Thuy
authors.initials: T
authors.lastname: Le
authors.forename: Estee M
authors.initials: EM
authors.lastname: Török
authors.forename: Nguyen T B
authors.initials: NT
authors.lastname: Yen
authors.forename: Tran T H
authors.initials: TT
authors.lastname: Chau
authors.forename: Suzanne
authors.initials: S
authors.lastname: Jurriaans
authors.forename: H Rogier
authors.initials: HR
authors.lastname: van Doorn
authors.forename: Rogier H
authors.initials: RH
authors.lastname: van Doorn
authors.forename: Menno D
authors.initials: MD
authors.lastname: de Jong
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Farrar
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Dunstan
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D060085:Coinfection / Q000188:drug therapy; D024882:Drug Resistance, Viral / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic; D015995:Prevalence; D017211:Treatment Failure; D014390:Tuberculosis, Meningeal / Q000150:complications*; D014744:Vietnam / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents