title: Sustained virological response on second-line antiretroviral therapy following virological failure in HIV-infected patients in rural South Africa.
abstract: OBJECTIVE
  This study aims to describe the virological, immunological and clinical efficacy of protease inhibitor (PI)-based second-line antiretroviral therapy (ART) in rural South Africa.
  
  
  METHODS
  An observational cohort study was performed on 210 patients (including 39 children) who initiated PI-based second-line therapy at least 12 months prior to data collection. Biannual clinical, immunological and virological monitoring was performed. Primary endpoints were adequate virological response (plasma HIV-1 RNA<400 copies/ml), full virological suppression (plasma HIV-1 RNA<50 copies/ml) and treatment failure (virological failure (plasma HIV-1 RNA>1000 after initial virological response) or on-going viremia (plasma HIV-1 RNA never<400 copies/ml for more than six months)). Data were analyzed by an on-treatment (OT) and intention-to-treat (ITT) approach. Analyses were primarily performed on the group of patients who switched following first-line virological failure.
  
  
  RESULTS
  Median duration of follow-up after switch to second-line treatment was 20 months [IQR 11-35]. 191 patients had switched to second-line ART due to first-line virological failure. 139/191 of them (72.8%, ITT) were in care and on treatment at the end of follow-up and 11/191 (5.8%, ITT) had died. After twelve months, an adequate virological response was seen in 92/128 patients (71.9%, OT), of which 78/128 (60.9%, OT) experienced full virological suppression. Virological response remained stable after 24 months. Virological efficacy was similar amongst adult and pediatric patients. As in first-line ART, we observed a lack of correlation between virological failure and WHO-defined immunological failure.
  
  
  CONCLUSIONS
  Good virological outcomes following first-line failure can be achieved with PI-based, second-line antiretroviral therapy in both adult and pediatric patients in rural South Africa. Retention rates were high and virological outcomes were sustainable during the two-year follow-up period, although persisting low-level viremia occurred in a subset of patients. The observed viro-immunological dissociation emphasizes the need for virological monitoring.
authors.affiliation: Department of Internal Medicine and Infectious Diseases, University Medical Centre Utrecht, Utrecht, The Netherlands. A.F.Schoffelen@umcutrecht.nl
authors.forename: Annelot F
authors.initials: AF
authors.lastname: Schoffelen
authors.forename: Annemarie M J
authors.initials: AM
authors.lastname: Wensing
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Tempelman
authors.forename: Sibyl P M
authors.initials: SP
authors.lastname: Geelen
authors.forename: Andy I M
authors.initials: AI
authors.lastname: Hoepelman
authors.forename: Roos E
authors.initials: RE
authors.lastname: Barth
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007223:Infant; D008297:Male; D012424:Rural Population; D013019:South Africa; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents