Low-Level K65R Mutation in HIV-1 Reverse Transcriptase of Treatment-Experienced Patients Exposed to Abacavir or Didanosine

Abstract

Prior therapy with ABC or ddI can result in a population genotype that shows K65R or L74V/I but does not reveal low-level K65R present in some patients. Subsequent treatment intensification with TDF resulted in a poor virologic response and may result in expansion of the preexisting K65R mutant.

Analysis of Low-Frequency Mutations Associated with Drug Resistance to Raltegravir before Antiretroviral Treatment

“…Studies of other antiretroviral drugs such as protease inhibitors (PIs) and reverse transcriptase inhibitors (RTIs) have shown that the presence of minority drug-resistant viruses before treatment may be associated with poor treatment responses following antiretroviral therapy (11,16,21,22,24). Recent studies have shown that minority RAL-associated drug-resistant mutations can also be detected in patients before treatment (2,3,12,13,17,18).…”

Development of an Allele-Specific PCR for Detection of the K65R Resistance Mutation in Patients Infected with Subtype C Human Immunodeficiency Virus Type 1

“…There is a need to explore the prevalence of certain mutations that are present as members of minority species in both drug-naïve and treatment-experienced patients (11,22). Conventional genotyping may fail to detect K65R due to the poor replicative capacity of viruses containing this mutation as well as to K65R/M184V and K65R/thymidine analogue mutation (TAM) bidirectional mutational antagonism (14,18,19).…”

Point Mutations Associated with HIV-1 Drug Resistance, Evasion of the Immune Response and AIDS Pathogenesis

“…L74V and K65R mutations rarely occur in the same viruses (Shafer & Schapiro, 2008). However, several patients harbouring HIV-1 species containing the L74V point mutation while receiving a regimen containing ABC or ddI have been found to have minor variants containing K65R (Descamps et al, 2006;Svarovskaia et al, 2007). On the other hand, K65R and M184V mutations are primarily found in patients receiving the NRTI backbone TDF/3TC (Gallant et al, 2004;Margot et al, 2006) and less commonly ABC/3TC (Moyle et al, 2005) or TDF/FTC (Gallant et al, 2006;Smith et al, 2008).…”

“…For instance, the presence of K65R or L74V (J. Eron, Jr. et al, 2006;Gallant et al, 2006;Moyle et al, 2005) point mutations ( Figure 2 and Table 2) in addition to the M184V is sufficient for high level resistance to ddI and ABC , particularly in patients with non-subtype B clades (Harrigan et al, 2000;Lanier et al, 2004a;Svarovskaia et al, 2007;M. A. Winters et al, 1997 .…”