Abstract: Both SHIV162p3(M184V) and SHIV162p3(K65R) replicated in vitro at high titers.
Abstract: Mucosal transmissibility studies using a repeat low-dose macaque model of rectal and vaginal transmission showed that both mutants were able to efficiently infect macaques only after the dose was increased to adjust for fitness reductions due to K65R and M184V.
Abstract: Our results in limited number of macaques suggest that the reduction in fitness due to M184V and K65R decreases virus transmissibility, and identify in vitro infectivity parameters that associate with mucosal transmissibility.
Abstract: Virus infectivity to virion particle ratios were 4- and 10-fold lower in SHIV162p3(M184V) and SHIV162p3(K65R
Failure of initial therapy with two nucleosides and efavirenz is not associated with early emergence of mutations in the C-terminus of HIV-1 reverse transcriptase.
PMID: 21350368
2011
Journal of acquired immune deficiency syndromes (1999)
Discussion: Other known polymerase domain mutations were not significantly associated with failure although, there were possible trends for K65R (p=0.13) and V106I/M (p=0.13).
Selection and characterization of HIV-1 with a novel S68 deletion in reverse transcriptase.
PMID: 21357304
2011
Antimicrobial agents and chemotherapy
Abstract: In vitro testing of HIV-1LAI-infected primary human lymphocytes treated with beta-D-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine (DFC; Dexelvucitabine; Reverset) produced a novel deletion of AGT at codon 68 (S68Delta) alone and in combination with K65R that differentially affects drug response.
Prevalence of HIV type 1 antiretroviral drug resistance mutations in Vietnam: a multicenter study.
PMID: 21366425
2011
AIDS research and human retroviruses
Abstract: The most common DRMs observed were M184V, V75A/M, M41L, and K65R (NRTI) and K103N, G190A, and Y181C (NNRTI).
Thermostable HIV-1 group O reverse transcriptase variants with the same fidelity as murine leukaemia virus reverse transcriptase.
Abstract: At temperatures above 52C, K65R and K65R/V75I retained similar levels of DNA polymerase activity to the wild-type HIV-1 group O RT, but were more efficient than HIV-1 group M subtype B and MLV RTs.
Abstract: Forward-mutation assays demonstrated that mutant RTs K65R, R78A and K65R/V75I showed >9-fold increased accuracy in comparison with the wild-type enzyme and were approximately two times more faithful than the MLV RT.
Abstract: However, K65R RT showed a higher tendency to intro
Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure.
Abstract: RT processivity assays showed a significant decrease in the processivity of K65N RT in comparison to K65R RT.
Abstract: Analysis of RCs revealed a significant loss in replication (p=0.004) for viruses containing K65N mutation in comparison to those with K65R mutation.
Abstract: In addition to K65R, the other mutation observed at HIV-1 RT codon 65 is K65N.
Abstract: We demonstrated that the significant decrease in RC of K65N viruses is related to the impaired RT processivity of K65N
HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis.
Result: Of the 16 infants with HIV drug resistance mutations at 6 mo, 13 (81%) had at least one NRTI resistance mutation (M184 I/V [n = 12], K65R [n = 2], and D67G [n = 1]), and six (38%) had NNRTI resistance mutations (K103N [n = 2], Y181 [n = 2], and G190A [n = 2]) (sequences submitted to GenBank, http://www.ncbi.nlm.nih.gov/Genbank/
Table: K65R
Discussion: A follow-up genotypic analysis on the detection of K65R mutation in breast milk is necessary.
Discussion: The appearance of K65R in one-quarter of the infants with resistance (Table 3) is of concern, and this might be due to a high level of 3TC in the breast milk.
Suboptimal adherence associated with virological failure and resistance mutations to first-line highly active antiretroviral therapy (HAART) in Bangalore, India.
Discussion: Although subtype C isolates have been reported to have a higher tendency to develop K65R, in contrast we observed a lower rate of K65R (3%) compared with global reports.
Drug resistance mutations in patients infected with HIV-2 living in Spain.
PMID: 21558334
2011
The Journal of antimicrobial chemotherapy
Abstract: In 24 antiretroviral-experienced patients with virological failure the most frequent major RT resistance mutations were M184V (58%), Q151M (33%) and K65R (21%), which are rarely seen thymidine analogue mutations.
Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure.
Abstract: Analysis of RNA secondary structure suggested that the latter was unlikely to impact on K65R development between subtypes and that Streisinger strand slippage during DNA synthesis at the homopolymeric nucleotide stretch of the subtype C K65 region might occur, resulting in misalignment of the primer and template.
Abstract: Consequently, slippage would lead to a deletion of the middle adenine of codon K65 and the production of a -1 frameshift mutation, which upon dislocation and realignment of the primer and template, would lead to development of the K65R mutation.
Abstract: Here, we report that DNA synthesis performed with subtype C templates consistently produced more K65R-containing transcripts than subtype B templates, regardless of the subtype-origin of the RT enzymes employed.