title: Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa.
abstract: BACKGROUND
  Episodes of viremia are common in African antiretroviral therapy (ART) programs. We sought to describe viremia, resuppression, and accumulation of resistance during first-line combination ART (cART) in South Africa.
  
  
  METHODS
  Retrospective analysis of a cohort receiving zidovudine, lamivudine, and either efavirenz or nevirapine with human immunodeficiency virus (HIV) RNA monitoring every 6 months. We assessed viremia (HIV RNA >1000 copies/mL after initial HIV RNA response) and resuppression (HIV RNA <400 copies/mL after viremia). Genotypic resistance testing was performed using stored plasma on a subset of patients at first detection of viremia and subsequently among patients with persistent viremia.
  
  
  RESULTS
  Between 2002 and 2006, 3727 patients initiated cART (median CD4, 147 cells/mm(3)). Of 1007 patients who developed viremia, 815 had subsequent HIV RNA assays, and 331 (41%) of these resuppressed without regimen switch. At identification of viremia, 45 (66%) of 68 patients had HIV-1 drug resistance, 42 (62%) had nonnucleoside reverse-transcriptase inhibitor (NNRTI)-resistance, 25 (37%) had M184V/I, and 4 (6%) had multi-nucleoside analogue drug mutations. By 12 months of persistent viremia among a subset of 14 patients with resistance testing to 12 months, 11 (78%) had nonnucleoside reverse-transcriptase inhibitor (NNRTI)-resistance, 8 (57%) had M184V/I, and 2 (14%) had multi-nucleoside analogue drug mutations. Resistance was associated with a reduced probability of resuppression; however, 50% of patients with NNRTI resistance resuppressed while receiving an NNRTI.
  
  
  CONCLUSIONS
  The majority of patients had NNRTI resistance mutations at detection of viremia. However, 41% resuppressed without regimen switch. Our findings support maximizing first-line use while minimizing risk of significant cross-resistance by implementing intensive adherence support and repeat HIV RNA testing 3-6 months after detecting viremia, with regimen switch only if viremia persists.
authors.affiliation: Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA. choffmann@jhmi.edu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hoffmann
authors.forename: Salome
authors.initials: S
authors.lastname: Charalambous
authors.forename: John
authors.initials: J
authors.lastname: Sim
authors.forename: Joanna
authors.initials: J
authors.lastname: Ledwaba
authors.forename: Graham
authors.initials: G
authors.lastname: Schwikkard
authors.forename: Richard E
authors.initials: RE
authors.lastname: Chaisson
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Fielding
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Churchyard
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.forename: Alison D
authors.initials: AD
authors.lastname: Grant
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D006678:HIV / Q000145:classification / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D013019:South Africa; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase