PLoS ONE (Jan 2013)

Accumulation of protease mutations among patients failing second-line antiretroviral therapy and response to salvage therapy in Nigeria.

  • Holly E Rawizza,
  • Beth Chaplin,
  • Seema T Meloni,
  • Kristin M Darin,
  • Oluremi Olaitan,
  • Kimberly K Scarsi,
  • Chika K Onwuamah,
  • Rosemary A Audu,
  • Philippe R Chebu,
  • Godwin E Imade,
  • Prosper Okonkwo,
  • Phyllis J Kanki

DOI
https://doi.org/10.1371/journal.pone.0073582
Journal volume & issue
Vol. 8, no. 9
p. e73582

Abstract

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BackgroundTo date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1(st)- and 2(nd)-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3(rd)-line (3 L) ART is needed. We aimed to examine the impact of maintaining patients on failing 2 L ART on the accumulation of protease (PR) mutations.Methods and findingsFrom 2004-2011, the Harvard/APIN PEPFAR Program provided ART to >100,000 people in Nigeria. Genotypic resistance testing was performed on a subset of patients experiencing 2 L failure, defined as 2 consecutive viral loads (VL)>1000 copies/mL after ≥6 months on 2 L. Of 6714 patients who received protease inhibitor (PI)-based ART, 673 (10.0%) met virologic failure criteria. Genotypes were performed on 61 samples. Patients on non-suppressive 2 L therapy for 24 months. Patients developed a median of 0.6 (IQR: 0-1.4) IAS PR mutations per 6 months on failing 2 L therapy. In 38% of failing patients no PR mutations were present. For patients failing >24 months, high- or intermediate-level resistance to lopinavir and atazanavir was present in 63%, with 5% to darunavir.ConclusionsThis is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a RLS. This information provides insight into the resistance cost of failing to switch non-suppressive 2 L regimens and highlights the issue of 3 L access.