title: Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy.
abstract: BACKGROUND
  The emergence of complex HIV-1 drug resistance mutations has been linked to the duration of time patients are on a failing antiretroviral drug regimen. This study reports on resistance profiles in a closely monitored subtype C infected cohort.
  
  
  METHODS
  A total of 812 participants were enrolled into the CIPRA-SA 'safeguard the household' study, viral loads were determined at 12-weekly intervals for 96 weeks. Virological failure was defined as either a <1.5 log decrease in viral load at week 12 or two consecutive viral load measurements of >1,000 RNA copies/ml after week 24. Regimens prescribed were in line with the South African roll-out programme (stavudine, lamivudine, efavirenz or nevirapine). Viral RNA was extracted from patients with virological failure, and pol reverse-transcriptase PCR and sequence analysis were performed to determine drug-resistant mutations.
  
  
  RESULTS
  Virological failure was observed in 83 participants on the first-line regimen during the study period, of which 61 (73%) had HIV-1 drug-resistant mutations. The M184V mutation was the most frequent (n=46; 65%), followed by K103N (46%) and Y181C (21%). Thymidine analogue mutations were infrequent (1%) and Q151M was not observed.
  
  
  CONCLUSIONS
  Drug resistance profiles were less complex than has been previously reported in South Africa using the same antiretroviral drug regimens. These data suggest that frequent viral load monitoring limits the level and complexity of resistance observed in HIV-1 subtype C, preserving susceptibility to second-line options.
authors.affiliation: University of the Witwatersrand, Johannesburg, South Africa. cwallis@mweb.co.za
authors.forename: Carole L
authors.initials: CL
authors.lastname: Wallis
authors.forename: Maria A
authors.initials: MA
authors.lastname: Papathanasopolous
authors.forename: Matthew
authors.initials: M
authors.lastname: Fox
authors.forename: Francesca
authors.initials: F
authors.lastname: Conradie
authors.forename: Prudence
authors.initials: P
authors.lastname: Ive
authors.forename: Catherine
authors.initials: C
authors.lastname: Orrell
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zeinecker
authors.forename: Ian
authors.initials: I
authors.lastname: Sanne
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: James
authors.initials: J
authors.lastname: McIntyre
authors.forename: Wendy
authors.initials: W
authors.lastname: Stevens
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000494:pharmacology / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D012367:RNA, Viral / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013019:South Africa; D018119:Stavudine / Q000494:pharmacology / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D018119:Stavudine; C098320:efavirenz