Clonal analyses of HIV quasispecies in patients harbouring plasma genotype with K65R mutation associated with thymidine analogue mutations or L74V substitution

Abstract

We analysed the quasispecies at a clonal level in patients whose plasma genotypic test harboured K65R with L74V or thymidine analogue mutations (TAM). We showed that the K65R and TAM such as M41L, D67N, T215Y/D, L210W and K219E can be borne by the same virus. We found no clone bearing both K65R and L74V substitutions. Moreover, the S68G and V75I mutations are not necessarily linked with K65R, and could thus have their own resistance effect.

Virological response to HIV-1 nucleoside/nucleotide reverse transcriptase inhibitors-based, tenofovir DF-including regimens in the ANRS Aquitaine Cohort

“…The rate of VF was also high in the DDI/ABC/TDF group (50%). Interestingly, the selection of either K65R or L74V seemed frequent in these two latter groups; these two mutations have been shown to co-exist very rarely in vivo (Colson et al, 2005;Wirden et al, 2005) and thus seem to represent two alternative pathways for virus escape to these regimens.…”

Intensification of a failing regimen with zidovudine may cause sustained virologic suppression in the presence of resensitising mutations including K65R

“…16 Meanwhile the advent of entry-and integrase-inhibitors as well as 2nd generation protease inhibitors and NNRTIs allow effective NRTI-sparing combinations for many patients today. However we demonstrated that zidovudine intensification in the presence of K65R in-vivo can result in sustained virological suppression, confirming hypersusceptibility observations invitro.…”

Coexistence of the K65R/L74V and/or K65R/T215Y mutations on the same HIV-1 genome

“…Recent clonal studies (Colson et al, 2005;Parikh et al, 2005;Valer et al, 2004) provide more subtle results: for instance, Parikh's et al (2005) found 65R with two TAMs or more including 215Y provided that there is the presence of 151M. A clonal analysis of two patients who had no zidovudine in their therapeutic regimen showed that K65R could be linked with TAMs (M41L, D67N, L210W, K219E) in several clones, and in a sole clone with T215Y (Wirden et al, 2005). The emergence of K65R could have probably been prevented with a sustained thymidine analogue selective pressure.…”