title: High prevalence of PI resistance in patients failing second-line ART in Vietnam.
abstract: BACKGROUND
  There are limited data from resource-limited settings on antiretroviral resistance mutations that develop in patients failing second-line PI ART.
  
  
  METHODS
  We performed a cross-sectional virological assessment of adults on second-line ART for ≥6 months between November 2006 and December 2011, followed by a prospective follow-up over 2 years of patients with virological failure (VF) at the Hospital for Tropical Diseases, Vietnam. VF was defined as HIV RNA concentrations ≥1000 copies/mL. Resistance mutations were identified by population sequencing of the pol gene and interpreted using the 2014 IAS-USA mutation list and the Stanford algorithm. Logistic regression modelling was performed to identify predictors of VF.
  
  
  RESULTS
  Two hundred and thirty-one patients were enrolled in the study. The median age was 32 years; 81.0% were male, 95.7% were on a lopinavir/ritonavir-containing regimen and 22 (9.5%) patients had VF. Of the patients with VF, 14 (64%) carried at least one major protease mutation [median: 2 (IQR: 1-3)]; 13 (59%) had multiple protease mutations conferring intermediate- to high-level resistance to lopinavir/ritonavir. Mutations conferring cross-resistance to etravirine, rilpivirine, tipranavir and darunavir were identified in 55%, 55%, 45% and 27% of patients, respectively. Higher viral load, adherence <95% and previous indinavir use were independent predictors of VF. The 2 year outcomes of the patients maintained on lopinavir/ritonavir included: death, 7 (35%); worsening virological/immunological control, 6 (30%); and virological re-suppression, 5 (25%). Two patients were switched to raltegravir and darunavir/ritonavir with good HIV control.
  
  
  CONCLUSIONS
  High-prevalence PI resistance was associated with previous indinavir exposure. Darunavir plus an integrase inhibitor and lamivudine might be a promising third-line regimen in Vietnam.
authors.affiliation: Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Vu Phuong
authors.initials: VP
authors.lastname: Thao
authors.affiliation: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Vo Minh
authors.initials: VM
authors.lastname: Quang
authors.affiliation: Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Day
authors.affiliation: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Nguyen Tran
authors.initials: NT
authors.lastname: Chinh
authors.affiliation: Hawaii Center for AIDS, University of Hawaii at Manoa, Honolulu, HI, USA.
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Shikuma
authors.affiliation: Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.affiliation: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Nguyen
authors.initials: N
authors.lastname: Van Vinh Chau
authors.affiliation: Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Guy E
authors.initials: GE
authors.lastname: Thwaites
authors.affiliation: The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Dunstan
authors.affiliation: Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK Hawaii Center for AIDS, University of Hawaii at Manoa, Honolulu, HI, USA thuyl@oucru.org.
authors.forename: Thuy
authors.initials: T
authors.lastname: Le
mesh_terms: D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D011446:Prospective Studies; D017211:Treatment Failure; D014744:Vietnam; D055815:Young Adult
chemical_list: D017320:HIV Protease Inhibitors