Viral Suppression Following Switch to Second-line Antiretroviral Therapy: Associations With Nucleoside Reverse Transcriptase Inhibitor Resistance and Subtherapeutic Drug Concentrations Prior to Switch

Details

• Alternative Title:
  J Infect Dis
• Personal Author:
  Johnston, Victoria ; Cohen, Karen ; Wiesner, Lubbe ; Morris, Lynn ; Ledwaba, Johanna ; Fielding, Katherine L. ; Charalambous, Salome ; Churchyard, Gavin ; Phillips, Andrew ; Grant, Alison D.
• Description:
  High rates of second-line antiretroviral treatment (ART) failure are reported. The association with resistance and nonadherence on switching to second-line ART requires clarification.|Using prospectively collected data from patients in South Africa, we constructed a cohort of patients switched to second-line ART (1 January 2003 through 31 December 2008). Genotyping and drug concentrations (lamivudine, nevirapine, and efavirenz) were measured on stored samples preswitch. Their association with viral load (VL) <400 copies/mL by 15 months was assessed using modified Poisson regression.|One hundred twenty-two of 417 patients (49% male; median age, 36 years) had genotyping (n = 115) and/or drug concentrations (n = 80) measured. Median CD4 count and VL at switch were 177 cells/µL (interquartile range [IQR], 77-263) and 4.3 log10 copies/mL (IQR, 3.8-4.7), respectively. Fifty-five percent (n = 44/80) had subtherapeutic drug concentrations preswitch. More patients with therapeutic vs subtherapeutic ART had resistance (n = 73): no major mutations (3% vs 51%), nonnucleoside reverse transcriptase inhibitor (94% vs 44%), M184V/I (94% vs 26%), and ≥ 1 thymidine analogue mutations (47% vs 18%), all P = .01; and nucleoside reverse transcriptase inhibitor (NRTI) cross-resistance mutations (26% vs 13%, P = .23). Following switch, 68% (n = 83/122) achieved VL <400 copies/mL. Absence of NRTI mutations and subtherapeutic ART preswitch were associated with failure to achieve VL <400 copies/mL.|Nonadherence, suggested by subtherapeutic ART with/without major resistance mutations, significantly contributed to failure when switching regimen. Unresolved nonadherence, not NRTI resistance, drives early second-line failure.
• Subjects:
  Adherence Adult Anti-HIV Agents Antiretroviral Therapy, Highly Active Drug Resistance, Viral Female Genotype HIV-1 HIV Infections Humans Major Articles And Brief Reports Male Middle Aged Mutation Prospective Studies Resistance Reverse Transcriptase Inhibitors RNA, Viral Second-line Antiretroviral Therapy Treatment Failure Viral Load Virological Failure

  More +
• Source:
  J Infect Dis. 2013; 209(5):711-720.
• DOI:
  http://dx.doi.org/10.1093/infdis/jit411
• Pubmed ID:
  23943851
• Pubmed Central ID:
  PMC3923537
• Document Type:
  Journal Article
• Funding:
  5U2GPS000811/PEPFAR/United States ; 087261/Z/08/Z/Wellcome Trust/United Kingdom ; 100714/Wellcome Trust/United Kingdom ; MR/K012126/1/Medical Research Council/United Kingdom ; U2G PS000811/PS/NCHHSTP CDC HHS/United States ; UM1 AI106701/AI/NIAID NIH HHS/United States ; UM1 AI068636/AI/NIAID NIH HHS/United States
• Name as Subject:
  United States. President's Emergency Plan For AIDS Relief (PEPFAR)
• Place as Subject:
  South Africa
• Volume:
  209
• Issue:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:2a7055b06dc197ee290361a393e5e7722809cdd798e9b04a99f8ddf78a1f3c8aa1a99e189e020528cbe636b57c1c71b0fd815bcff5dcde904cb6ab14d73ffb8b
• Download URL:
  https://stacks.cdc.gov/view/cdc/43625/cdc_43625_DS1.pdf
• File Type:
  [PDF - 301.77 KB ]