title: HIV-1 antiretroviral drug resistance patterns in patients failing NNRTI-based treatment: results from a national survey in South Africa.
abstract: Routine HIV-1 antiretroviral drug resistance testing for patients failing NNRTI-based regimens is not recommended in resource-limited settings. Therefore, surveys are required to monitor resistance profiles in patients failing ART.
  
  
  
  A cross-sectional survey was conducted amongst patients failing NNRTI-based regimens in the public sector throughout South Africa. Virological failure was defined as two consecutive HIV-1 viral load results >1000 RNA copies/mL. Pol sequences were obtained using RT-PCR and Sanger sequencing and submitted to Stanford HIVdb v7.0.1.
  
  
  
  A total of 788 sequences were available for analysis. Most patients failed a tenofovir-based NRTI backbone (74.4%) in combination with efavirenz (82.1%) after median treatment duration of 36 months. K103N (48.9%) and V106M (34.9%) were the most common NNRTI mutations. Only one-third of patients retained full susceptibility to second-generation NNRTIs such as etravirine (36.5%) and rilpivirine (27.3%). After M184V/I (82.7%), K65R was the most common NRTI mutation (45.8%). The prevalence of K65R increased to 57.5% in patients failing a tenofovir regimen without prior stavudine exposure. Cross-resistance to NRTIs was often observed, but did not seem to affect the predicted activity of zidovudine as 82.9% of patients remained fully susceptible to this drug.
  
  
  
  The introduction of tenofovir-based first-line regimens has dramatically increased the prevalence of K65R mutations in the HIV-1-infected South African population. However, most patients failing tenofovir-based regimens remained fully susceptible to zidovudine. Based on these data, there is currently no need to change either the recommended first- or second-line ART regimens in South Africa.
authors.affiliation: Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa kim.steegen@nhls.ac.za.
authors.forename: K
authors.initials: K
authors.lastname: Steegen
authors.affiliation: National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: M
authors.initials: M
authors.lastname: Bronze
authors.affiliation: Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: M A
authors.initials: MA
authors.lastname: Papathanasopoulos
authors.affiliation: National Health Laboratory Service, Johannesburg, South Africa.|Division of Medical Virology, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: G
authors.initials: G
authors.lastname: van Zyl
authors.affiliation: National Health Laboratory Service, Johannesburg, South Africa.|Department of Medical Microbiology and Virology, University of the Free State, Bloemfontein, South Africa.
authors.forename: D
authors.initials: D
authors.lastname: Goedhals
authors.affiliation: Department of Internal Medicine, Klerksdorp Tshepong Hospital Complex, Klerksdorp, South Africa.|Department of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa.|Perinatal HIV Research Unit, Johannesburg, South Africa.
authors.forename: E
authors.initials: E
authors.lastname: Variava
authors.affiliation: Center for Global Health and Development, Boston University School of Public Health, Boston, MA, USA.|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: W
authors.initials: W
authors.lastname: MacLeod
authors.affiliation: Right to Care, Johannesburg, South Africa.
authors.forename: I
authors.initials: I
authors.lastname: Sanne
authors.affiliation: Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa.|National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: W S
authors.initials: WS
authors.lastname: Stevens
authors.affiliation: Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa.|National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: S
authors.initials: S
authors.lastname: Carmona
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013019:South Africa; D017211:Treatment Failure; D019562:Viral Load; D055815:Young Adult; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D044966:Anti-Retroviral Agents; D054302:pol Gene Products, Human Immunodeficiency Virus