title: No Evidence That HIV-1 Subtype C Infection Compromises the Efficacy of Tenofovir-Containing Regimens: Cohort Study in the United Kingdom.
abstract: Concern has been expressed that tenofovir-containing regimens may have reduced effectiveness in the treatment of human immunodeficiency virus type 1 (HIV-1) subtype C infections because of a propensity for these viruses to develop a key tenofovir-associated resistance mutation. We evaluated whether subtype influenced rates of virological failure in a cohort of 8746 patients from the United Kingdom who received a standard tenofovir-containing first-line regimen and were followed for a median of 3.3 years. In unadjusted analyses, the rate of failure was approximately 2-fold higher among patients infected with subtype C virus as compared to those with subtype B virus (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.50-2.31; P < .001). However, the increased risk was greatly attenuated in analyses adjusting for demographic and clinical factors (adjusted HR, 1.14; 95% CI, .83-1.58; P = .41). There were no differences between subtypes C and subtypes non-B and non-C in either univariate or multivariate analysis. These observations imply there is no intrinsic effect of viral subtype on the efficacy of tenofovir-containing regimens.
authors.affiliation: MRC Clinical Trials Unit at UCL.
authors.forename: Ellen
authors.initials: E
authors.lastname: White
authors.affiliation: Public Health England, Birmingham Heartlands Hospital.
authors.forename: Erasmus
authors.initials: E
authors.lastname: Smit
authors.affiliation: Brighton and Sussex Hospitals NHS Trust, United Kingdom.
authors.forename: Duncan
authors.initials: D
authors.lastname: Churchill
authors.affiliation: HIV i-Base.
authors.forename: Simon
authors.initials: S
authors.lastname: Collins
authors.affiliation: Health Service Laboratories, Royal Free Hospital, London.
authors.forename: Clare
authors.initials: C
authors.lastname: Booth
authors.affiliation: MRC Clinical Trials Unit at UCL.
authors.forename: Anna
authors.initials: A
authors.lastname: Tostevin
authors.affiliation: Department of Infection and Population Health.
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
authors.affiliation: Division of Infection and Immunity, University College London.|Africa Centre for Population Health, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
authors.affiliation: MRC Clinical Trials Unit at UCL.
authors.forename: David T
authors.initials: DT
authors.lastname: Dunn
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D000068698:Tenofovir / Q000627:therapeutic use*; D017211:Treatment Failure; D006113:United Kingdom
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir
keywords: HIV-1; K65R; subtype; tenofovir; virological failure