title: Evolution of drug resistance during 48 weeks of zidovudine/lamivudine/tenofovir in the absence of real-time viral load monitoring.
abstract: OBJECTIVE
  To describe the resistance mutations selected by a first-line regimen of zidovudine/lamivudine/tenofovir in the absence of real-time viral load monitoring.
  
  
  METHODS
  A substudy of 300 participants from the Development of Antiretroviral Therapy in Africa trial in Uganda and Zimbabwe, which compared managing antiretroviral therapy with and without laboratory monitoring.
  
  
  METHODS
  Stored plasma samples from selected time points were assayed retrospectively for HIV-1 RNA. The pol gene in all baseline samples and those with HIV RNA >1000 copies per milliliter at weeks 24 and 48 were sequenced.
  
  
  RESULTS
  The proportion with HIV RNA >1000 copies per milliliter increased from 15% at 24 weeks to 24% at 48 weeks. Eighteen of 31 (58%) genotyped samples at 24 weeks had ≥ 1 major nucleoside reverse transcriptase inhibitor-associated mutations compared with 41 of 47 (87%) at 48 weeks. Excluding 1 nonadherent patient, a mean of 2.0 (95% confidence interval: 1.3 to 2.8) thymidine analogue mutations (TAMs) developed between weeks 24 and 48 among 14 patients with HIV RNA >1000 copies per milliliter at both time points. K65R was detected in 8 of 63 (13%) patients and was negatively associated with number of TAMs (P = 0.01) but not viral subtype (P = 0.30).
  
  
  CONCLUSIONS
  A high rate of acquisition of TAMs, but not of K65R, among patients with prolonged viraemia was observed. However, most patients were virologically suppressed at 48 weeks, and long-term clinical and immunological outcomes in the Development of Antiretroviral Therapy in Africa trial were favorable.
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
authors.forename: Fred
authors.initials: F
authors.lastname: Lyagoba
authors.forename: David T
authors.initials: DT
authors.lastname: Dunn
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
authors.forename: Cissy
authors.initials: C
authors.lastname: Kityo
authors.forename: Val
authors.initials: V
authors.lastname: Robertson
authors.forename: Stephano
authors.initials: S
authors.lastname: Tugume
authors.forename: James
authors.initials: J
authors.lastname: Hakim
authors.forename: Paula
authors.initials: P
authors.lastname: Munderi
authors.forename: Mike
authors.initials: M
authors.lastname: Chirara
authors.forename: Nicaise
authors.initials: N
authors.lastname: Ndembi
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Goodall
authors.forename: David L
authors.initials: DL
authors.lastname: Yirrell
authors.forename: Andy
authors.initials: A
authors.lastname: Burke
authors.forename: Charles F
authors.initials: CF
authors.lastname: Gilks
authors.forename: Pontiano
authors.initials: P
authors.lastname: Kaleebu
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral / Q000235:genetics; D005838:Genotype; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D009154:Mutation; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D000068698:Tenofovir; D013997:Time Factors; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D019259:Lamivudine; D015215:Zidovudine; D000068698:Tenofovir; D000225:Adenine