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- Title
Prevalence of pre-existing resistance-associated mutations to rilpivirine, emtricitabine and tenofovir in antiretroviral-naive patients infected with B and non-B subtype HIV-1 viruses.
- Authors
Lambert-Niclot, S.; Charpentier, C.; Storto, A.; Fofana, D. B.; Soulié, C.; Fourati, S.; Visseaux, B.; Wirden, M.; Morand-Joubert, L.; Masquelier, B.; Flandre, P.; Calvez, V.; Descamps, D.; Marcelin, A.-G.
- Abstract
Objectives The prevalence of rilpivirine, emtricitabine and tenofovir resistance-associated mutations (RAMs), described in vitro and in vivo, was determined in antiretroviral-naive patients. Patients and methods From 2008 to 2011, 1729 treatment-naive patients were tested for resistance by bulk sequencing. We studied the primary rilpivirine RAMs (K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, H221Y, F227C and M230I/L) and other potential rilpivirine-associated mutations (V90I, L100I, K101T, E138S, V179D/I, Y188L, V189I, G190A/E/S and M230V). We also studied the M184V/I and K65R mutations for emtricitabine and tenofovir, respectively. Results Among 1729 sequences, half of patients had B-subtype viruses and the other half non-B (with 26.7% CRF02, n = 461). Primary rilpivirine RAMs were infrequent (4.6%, n = 79) and the most prevalent were E138A (3%, n = 52), E138K, (0.3%, n = 5), H221Y (0.3%, n = 5), E138G (0.2%, n = 4) and Y181C (0.2%, n = 4). The frequency of the primary rilpivirine RAMs was similar between B and non-B subtypes. The other potential rilpivirine-associated mutations that were most prevalent were V179I (8.4%, n = 145), V90I (3.8%, n = 65) and V189I (2.3%, n = 40). The common V179I, V189I and V90I polymorphisms have not been associated with virological failure in Phase 3 clinical studies. By the ANRS algorithm, 4.9% (n = 84) of samples were resistant to rilpivirine, 3.7% (n = 32) of B-subtype viruses versus 6% (n = 52) of non-B-subtype viruses (P = 0.02, χ2 test). The prevalence of K65R and M184I/V was 0.06% (1/1729) and 1% (18/1729), respectively. The prevalence of K103N was 2% (35/1729). Conclusions The prevalence of rilpivirine, emtricitabine and tenofovir resistance mutations was very low in antiretroviral-naive patients. The prevalence of resistance to rilpivirine (4.9%, n = 84) was not statistically different from the prevalence of efavirenz and nevirapine resistance in our population.
- Subjects
RILPIVIRINE; ANTI-HIV agents; HIV infections; THERAPEUTICS; EMTRICITABINE-tenofovir; TENOFOVIR
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2013, Vol 68, Issue 6, p1237
- ISSN
0305-7453
- Publication type
Article
- DOI
10.1093/jac/dkt003