title: HIV drug resistance levels in adults failing first-line antiretroviral therapy in an urban and a rural setting in South Africa.
abstract: Urban and rural HIV treatment programmes face different challenges in the long-term management of patients. There are few studies comparing drug resistance profiles in patients accessing treatment through these programmes. The aim of this study was to perform such a comparison.
  
  
  
  HIV drug resistance data and associated treatment and monitoring information for adult patients failing first-line therapy in an urban and a rural programme were collected. Data were curated and managed in SATuRN RegaDB before statistical analysis using Microsoft Excel 2013 and stata Ver14, in which clinical parameters, resistance profiles and predicted treatment responses were compared.
  
  
  
  Data for 595 patients were analysed: 492 patients from a rural setting and 103 patients from an urban setting. The urban group had lower CD4 counts at treatment initiation than the rural group (98 vs. 126 cells/μL, respectively; P = 0.05), had more viral load measurements performed per year (median 3 vs. 1.4, respectively; P < 0.01) and were more likely to have no drug resistance mutations detected (35.9% vs. 11.2%, respectively; P < 0.01). Patients in the rural group were more likely to have been on first-line treatment for a longer period, to have failed for longer, and to have thymidine analogue mutations. Notwithstanding these differences, the two groups had comparable predicted responses to the standard second-line regimen, based on the genotypic susceptibility score. Mutations accumulated in a sigmoidal fashion over failure duration.
  
  
  
  The frequency and patterns of drug resistance, as well the intensity of virological monitoring, in adults with first-line therapy failure differed between the urban and rural sites. Despite these differences, based on the genotypic susceptibility scores, the majority of patients across the two sites would be expected to respond well to the standard second-line regimen.
authors.affiliation: Department of Immunology, Institute for Cellular and Molecular Medicine, University of Pretoria, Pretoria, South Africa.
authors.forename: T M
authors.identifier: 0000-0003-4066-922X
authors.initials: TM
authors.lastname: Rossouw
authors.affiliation: South African Department of Science and Technology/National Research Foundation Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), Stellenbosch University, Stellenbosch, South Africa.
authors.forename: M
authors.initials: M
authors.lastname: Nieuwoudt
authors.affiliation: Department of Infectious Diseases, Stanford University, Stanford, CA, USA.|Africa Centre Population Health, University of KwaZulu-Natal, South Africa.
authors.forename: J
authors.initials: J
authors.lastname: Manasa
authors.affiliation: Department of Immunology, Institute for Cellular and Molecular Medicine, University of Pretoria, Pretoria, South Africa.
authors.forename: G
authors.initials: G
authors.lastname: Malherbe
authors.affiliation: Africa Centre Population Health, University of KwaZulu-Natal, South Africa.|Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Lessells
authors.affiliation: Africa Centre Population Health, University of KwaZulu-Natal, South Africa.
authors.forename: S
authors.initials: S
authors.lastname: Pillay
authors.affiliation: Africa Centre Population Health, University of KwaZulu-Natal, South Africa.
authors.forename: S
authors.initials: S
authors.lastname: Danaviah
authors.affiliation: Department of Immunology, Institute for Cellular and Molecular Medicine, University of Pretoria, Pretoria, South Africa.
authors.forename: P
authors.initials: P
authors.lastname: Mahasha
authors.affiliation: Department of Immunology, Institute for Cellular and Molecular Medicine, University of Pretoria, Pretoria, South Africa.
authors.forename: G
authors.initials: G
authors.lastname: van Dyk
authors.affiliation: Africa Centre Population Health, University of KwaZulu-Natal, South Africa.|Research Department of Infection, University College London, London, UK.|School of Laboratory Medicine and Medical Sciences, Nelson R. Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: T
authors.initials: T
authors.lastname: de Oliveira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D005260:Female; D060005:Genotyping Techniques; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012424:Rural Population; D013019:South Africa / Q000453:epidemiology; D017211:Treatment Failure; D014505:Urban Population; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents
keywords: HIV-1; drug resistance; rural; urban.