title: CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone.
abstract: OBJECTIVE
  CD4 count decline often triggers antiretroviral regimen switches in resource-limited settings, even when viral load testing is available. We therefore compared CD4 failure and CD4 trends in patients with viraemia with or without antiretroviral resistance.
  
  
  METHODS
  Retrospective cohort study investigating the association of HIV drug resistance with CD4 failure or CD4 trends in patients on first-line antiretroviral regimens during viraemia. Patients with viraemia (HIV RNA >1000 copies/ml) from two HIV treatment programmes in South Africa (n = 350) were included. We investigated the association of M184V and NNRTI resistance with WHO immunological failure criteria and CD4 count trends, using chi-square tests and linear mixed models.
  
  
  RESULTS
  Fewer patients with the M184V mutation reached immunologic failure criteria than those without: 51 of 151(34%) vs. 90 of 199 (45%) (P = 0.03). Similarly, 79 of 220 (36%) patients, who had major NNRTI resistance, had immunological failure, whereas 62 of 130 (48%) without (chi-square P = 0.03) did. The CD4 count decline among patients with the M184V mutation was 2.5 cells/mm(3) /year, whereas in those without M184V it was 14 cells/mm(3) /year (P = 0.1), but the difference in CD4 count decline with and without NNRTI resistance was marginal.
  
  
  CONCLUSIONS
  Our data suggest that CD4 count monitoring may lead to inappropriate delayed therapy switches for patients with HIV drug resistance. Conversely, patients with viraemia but no drug resistance are more likely to have a CD4 count decline and thus may be more likely to be switched to a second-line regimen.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Aurum Institute, Johannesburg, South Africa.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hoffmann
authors.affiliation: National Health Laboratory Service, Tygerberg, Cape Town, South Africa.|Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Jean
authors.initials: J
authors.lastname: Maritz
authors.affiliation: National Health Laboratory Service, Tygerberg, Cape Town, South Africa.|Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Gert U
authors.initials: GU
authors.lastname: van Zyl
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D003657:Decision Making; D016903:Drug Monitoring; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013019:South Africa; D017211:Treatment Failure; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy
chemical_list: D019380:Anti-HIV Agents
keywords: HIV-1 drug resistance; HIV-1 viral load testing; M184V; M184V, Major NNRTI drug resistance mutations; adherence; adherencia; compliance; critères d’échec immunologique; détermination de la charge virale du VIH-1; fallo inmunológico; first-line antiretroviral therapy; immunologic failure criteria; mutaciones de resistencia a medicamentos NNRTI; mutations NNRTI de résistance majeure aux médicaments; prueba de carga viral VIH-1; resistencia a medicamentos VIH-1; résistance aux médicaments du VIH-1; terapia antirretroviral de primera línea; traitement antirétroviral de première ligne