title: Moderate Levels of Pre-Treatment HIV-1 Antiretroviral Drug Resistance Detected in the First South African National Survey.
abstract: BACKGROUND
  In order to assess the level of transmitted and/or pre-treatment antiretroviral drug resistance to HIV-1, the World Health Organization (WHO) recommends that regular surveys are conducted. This study's objective was to assess the frequency of HIV-1 antiretroviral drug resistance in patients initiating antiretroviral treatment (ART) in the public sector throughout South Africa.
  
  
  METHODS
  A prospective cross-sectional survey was conducted using probability proportional to size sampling. This method ensured that samples from each province were proportionally collected, based on the number of patients receiving ART in each region. Samples were collected between March 2013 and October 2014. Pol sequences were obtained using RT-PCR and Sanger sequencing and submitted to the Stanford Calibrated Population Resistance tool v6.0.
  
  
  RESULTS
  A total of 277 sequences were available for analysis. Most participants were female (58.8%) and the median age was 34 years (IQR: 29-42). The median baseline CD4-count was 149 cells/mm3 (IQR: 62-249) and, based on self-reporting, participants had been diagnosed as HIV-positive approximately 44 days prior to sample collection (IQR: 23-179). Subtyping revealed that 98.2% were infected with HIV-1 subtype C. Overall, 25 out of 277 patients presented with ≥1 surveillance drug resistance mutation (SDRM, 9.0%, 95% CI: 6.1-13.0%). Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations were the most numerous mutations detected (n = 23). Only two patients presented with a protease inhibitor (PI) mutation. In four patients ≥4 SDRMs were detected, which might indicate that these patients were not truly ART-naïve or were infected with a multi-resistant virus.
  
  
  CONCLUSIONS
  These results show that the level of antiretroviral drug resistance in ART-naïve South Africans has reached moderate levels, as per the WHO classification. Therefore, regular surveys of pre-treatment drug resistance levels in all regions of South Africa is highly recommended to monitor the changing levels of pre-treatment antiretroviral drug resistance.
authors.affiliation: Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Kim
authors.initials: K
authors.lastname: Steegen
authors.affiliation: Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa.|National Health Laboratory Services, Johannesburg, South Africa.
authors.forename: Sergio
authors.initials: S
authors.lastname: Carmona
authors.affiliation: National Health Laboratory Services, Johannesburg, South Africa.
authors.forename: Michelle
authors.initials: M
authors.lastname: Bronze
authors.affiliation: Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Papathanasopoulos
authors.affiliation: National Health Laboratory Services, Johannesburg, South Africa.|Division of Medical Virology, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Gert
authors.initials: G
authors.lastname: van Zyl
authors.affiliation: National Health Laboratory Services, Johannesburg, South Africa.|Department of Medical Microbiology and Virology, University of the Free State, Bloemfontein, South Africa.
authors.forename: Dominique
authors.initials: D
authors.lastname: Goedhals
authors.affiliation: Center for Global Health and Development, Boston University School of Public Health, Boston, Massachusetts, United States of America.|Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: William
authors.initials: W
authors.lastname: MacLeod
authors.affiliation: Right to Care, Johannesburg, South Africa.
authors.forename: Ian
authors.initials: I
authors.lastname: Sanne
authors.affiliation: Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa.|National Health Laboratory Services, Johannesburg, South Africa.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Stevens
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology* / Q000235:genetics / Q000821:virology; D006679:HIV Seropositivity / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013019:South Africa / Q000453:epidemiology; D011795:Surveys and Questionnaires; D014944:World Health Organization
chemical_list: D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D018894:Reverse Transcriptase Inhibitors