title: Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens.
abstract: South Africa's national antiretroviral (ARV) treatment program expanded in 2010 to include the nucleoside reverse transcriptase (RT) inhibitors (NRTI) tenofovir (TDF) for adults and abacavir (ABC) for children. We investigated the associated changes in genotypic drug resistance patterns in patients with first-line ARV treatment failure since the introduction of these drugs, and protease inhibitor (PI) resistance patterns in patients who received ritonavir-boosted lopinavir (LPV/r)-containing therapy.
  
  
  
  We analysed ARV treatment histories and HIV-1 RT and protease mutations in plasma samples submitted to the Tygerberg Academic Hospital National Health Service Laboratory.
  
  
  
  Between 2006 and 2012, 1,667 plasma samples from 1,416 ARV-treated patients, including 588 children and infants, were submitted for genotypic resistance testing. Compared with 720 recipients of a d4T or AZT-containing first-line regimen, the 153 recipients of a TDF-containing first-line regimen were more likely to have the RT mutations K65R (46% vs 4.0%; p<0.001), Y115F (10% vs. 0.6%; p<0.001), L74VI (8.5% vs. 1.8%; p<0.001), and K70EGQ (7.8% vs. 0.4%) and recipients of an ABC-containing first-line regimen were more likely to have K65R (17% vs 4.0%; p<0.001), Y115F (30% vs 0.6%; p<0.001), and L74VI (56% vs 1.8%; p<0.001). Among the 490 LPV/r recipients, 55 (11%) had ≥1 LPV-resistance mutations including 45 (9.6%) with intermediate or high-level LPV resistance. Low (20 patients) and intermediate (3 patients) darunavir (DRV) cross resistance was present in 23 (4.6%) patients.
  
  
  
  Among patients experiencing virological failure on a first-line regimen containing two NRTI plus one NNRTI, the use of TDF in adults and ABC in children was associated with an increase in four major non- thymidine analogue mutations. In a minority of patients, LPV/r-use was associated with intermediate or high-level LPV resistance with predominantly low-level DRV cross-resistance.
authors.affiliation: National Health Laboratory Service, Tygerberg, Coastal Branch, South Africa ; Division of Medical Virology, Stellenbosch University, Faculty of Medicine and Health Sciences, Parow, South Africa.
authors.forename: Gert U
authors.initials: GU
authors.lastname: Van Zyl
authors.forename: Tommy F
authors.initials: TF
authors.lastname: Liu
authors.forename: Mathilda
authors.initials: M
authors.lastname: Claassen
authors.forename: Susan
authors.initials: S
authors.lastname: Engelbrecht
authors.forename: Tulio
authors.initials: T
authors.lastname: de Oliveira
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Preiser
authors.forename: Natasha T
authors.initials: NT
authors.lastname: Wood
authors.forename: Simon
authors.initials: S
authors.lastname: Travers
authors.forename: Robert W
authors.initials: RW
authors.lastname: Shafer
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013019:South Africa; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease