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  • Open Access

Mutations in the protease gene associated with virological failure to lopinavir-containing regimens in clinical samples

  • 1,
  • 1,
  • 2,
  • 3,
  • 4,
  • 5 and
  • 1
Journal of the International AIDS Society200811 (Suppl 1) :P191

  • Published:


  • Interquartile Range
  • Clinical Sample
  • Resistance Mutation
  • Saquinavir
  • Resistance Testing

Purpose of the study

Lopinavir/ritonavir (LPV/r) is increasingly being introduced in resource-limited settings as second-line therapy. Data on selection of resistance mutations (RAMs) in treatment-experienced populations failing LPV/r could provide insight into future ramifications of this strategy. We investigated the RAMs in patients with prior or current LPV/r failure.


We identified 195 samples from multi-treated patients submitted for routine resistance testing. Seventy-one (36%) never received LPV/r, 75 (38.5%) had previously failed LPV/r, and 49 (25%) were currently on LPV/r. Medians, interquartile ranges or percentages, Kruskal-Wallis, χ2 or Fisher test were used whenever appropriate.

Summary of results

Median CD4 282 cells/μl (IQR:252), HIV-1 VL 4.17 log10 (IQR 1.35), and duration of HIV infection 13 years. Number of NRTI, NNRTI and PI RAMs: 5 (IQR:4), 1 (IQR:1), and 6 (IQR:4), respectively. Patients exposed to LPV/r had received more HAART regimens (p < 0.001), PIs (p < 0.001), and NRTIs (p < 0.001). RAMs significantly associated with prior or current LPV/r exposure were: L10I/F (p = 0.02, p = 0.001), K20R (p = 0.023), L24I (p = 0.01), L33F (p < 0.001), M36I (p = 0.029), M46I/L (p = 0.023, p = 0.003), I47V (p = 0.022), G48V (p = 0.08), F53L (p = 0.017), I54V (p < 0.001), A71V (p < 0.001), G73S (p = 0.008), V82A (p < 0.001), I84V (p < 0.001), and L90M (p = 0.037). Two NRTI mutations were also associated with LPV/r failure: E44D (p = 0.002) and V118I (p = 0.048). L76V was found in only one sample. RAMs associated only with current (and not previous) LPV/r failure were: L33F, M36I, M46I, I47V, G48V, A71V, G73S, I84V, L90M. These RAMs are all included in the IAS-USA LPV/r list, except M36I and G48V, found to be associated with prior saquinavir use (p = 0.02 and p < 0.001, respectively). Mutations included in the IAS-USA list for LPV but not found to be associated with LPV/r previous or current failure: L10R/V, K20M, V32I, I47A, I50V, I54L/A/M/T/S, L63P, A71T, I76V, and V82F/T/S.


In multi-treated patients, L33F, M36I, M46I, I47V, G48V, A71V, G73S, I84V, L90M, but not L10R/V, K20M, V32I, I47A, I50V, I54L/A/M/T/S, L63P, A71T, I76V, and V82F/T/S may be over-represented in LPV/r failure. Enrichment of these mutations should be expected in populations receiving widespread salvage with LPV/r. This may assist in considering future options, together with previous use of other PI and subtype prevalence.

Authors’ Affiliations

University Hospital Germans Trias, Badalona, Spain
Universitat Politècnica de Catalunya, Barcelona, Spain
Hospital Sant Pau, Barcelona, Spain
Hospital Xeral Cies, Vigo, Spain
National Haemophilia Center, Tel Aviv, Israel


© Santos et al; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.