title: Treatment failure and drug resistance is more frequent in HIV-1 subtype D versus subtype A-infected Ugandans over a 10-year study period.
abstract: OBJECTIVE
  To determine the impact of HIV-1 subtype on treatment outcomes and the emergence of drug resistance in the resource limited setting of Kampala, Uganda.
  
  
  METHODS
  The Joint Clinical Research Centre (JCRC) in Kampala, Uganda has provided over 2000 drug-resistant genotypes (DRGs) over the past 10 years as standard of care for patients failing therapy and 1403 from treatment-naive and experienced patients over the past 10 years have been analyzed for this study.
  
  
  METHODS
  Viral loads, CD4 cell count, treatment histories and other relevant clinical data was compared with the infecting HIV-1 subtype and DRGs of Ugandan patients failing treatment.
  
  
  RESULTS
  Patients failing HAART with DRGs (n = 937) were more frequently infected with subtype D than expected on the basis of the subtype distribution in the treatment-naive population (n = 655) in Kampala (P < 0.001). Higher proportions of treatment failures among subtype D-infected patients were driven by resistance to nucleoside reverse transcriptase inhibitors (NRTI) (P < 0.0002) more than to non-NRTIs (P > 0.04) or protease inhibitors.
  
  
  CONCLUSIONS
  Higher rates of treatment failure among subtype D as compared with subtype A-infected Ugandans was analogous to the faster disease progression in subtype D-infected patients. The mechanism(s) by which drug resistance may emerge faster in subtype D HIV-1 may relate to higher replicative fitness and increased propensity for a CXCR4 tropism.
authors.forename: Fred
authors.initials: F
authors.lastname: Kyeyune
authors.forename: Immaculate
authors.initials: I
authors.lastname: Nankya
authors.forename: Samar
authors.initials: S
authors.lastname: Metha
authors.forename: Juliet
authors.initials: J
authors.lastname: Akao
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Ndashimye
authors.forename: Denis M
authors.initials: DM
authors.lastname: Tebit
authors.forename: Benigno
authors.initials: B
authors.lastname: Rodriguez
authors.forename: Cissy
authors.initials: C
authors.lastname: Kityo
authors.forename: Robert A
authors.initials: RA
authors.lastname: Salata
authors.forename: Peter
authors.initials: P
authors.lastname: Mugyenyi
authors.forename: Eric
authors.initials: E
authors.lastname: Arts
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D017211:Treatment Failure; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents