The K101P and K103R/V179D Mutations in Human Immunodeficiency Virus Type 1 Reverse Transcriptase Confer Resistance to Nonnucleoside Reverse Transcriptase Inhibitors

Parkin, Neil; Gupta, Surabhi; Chappey, Colombe; Petropoulos, Christos J.

doi:10.1128/aac.50.1.351-354.2006

Cited by 40 publications

(35 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is interesting that K103S, a rare mutation that causes over 10-fold decreased NNRTI susceptibility , was detected in two patients, one of them NNRTI-naïve. Combination of K103R with V179D, which reduces susceptibility to NNRTIs [Parkin et al, 2006], was detected in two samples, one of them from a drug-naïve patient.…”

Section: Discussionmentioning

confidence: 98%

Antiretroviral drug resistance and phylogenetic diversity of HIV‐1 in Chile

Ríos

Delgado

Pérez-Álvarez

et al. 2007

Journal of Medical Virology

View full text Add to dashboard Cite

This study reports the analysis of human immunodeficiency virus type 1 (HIV-1) protease (PR) and reverse transcriptase (RT) coding sequences from 136 HIV-1-infected subjects from Chile, 66 (49%) of them under antiretroviral (ARV) treatment. The prevalence of mutations conferring high or intermediate resistance levels to ARVs was 77% among treated patients and 2.5% among drug-naïve subjects. The distribution of resistance prevalence in treated patients by drug class was 61% to nucleoside RT inhibitors, 84% to nonnucleoside RT inhibitors, and 46% to PR inhibitors. Phylogenetic analysis revealed that 115 (85%) subjects were infected with subtype B viruses, 1 with a subtype F1 virus, and 20 (15%) carried BF intersubtype recombinants. Most BF recombinants grouped into two clusters, one related to CRF12_BF, while the other could represent a new circulating recombinant form (CRF). In conclusion, this is the first report analysing the prevalence of ARV resistance which includes patients under HAART from Chile. Additionally, phylogenetic analysis of the PR-RT coding sequences reveals the presence of BF intersubtype recombinants.

show abstract

Section: Discussionmentioning

confidence: 98%

Antiretroviral drug resistance and phylogenetic diversity of HIV‐1 in Chile

Ríos

Delgado

Pérez-Álvarez

et al. 2007

Journal of Medical Virology

View full text Add to dashboard Cite

show abstract

“…In contrast, K103R can reduce NVP susceptibility when V179D is also present. 11 The woman in our study with K103R did not have V179D. Other mutations at codon 103 that can confer resistance to …”

mentioning

confidence: 92%

Short Communication:HIV Type 1 Variants with Nevirapine Resistance Mutations Are Rarely Detected in Antiretroviral Drug-Naive African Women with Subtypes A, C, and D

Church

Hudelson

Guay

et al. 2007

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

K103N is frequently detected in HIV-infected women after single dose (SD) nevirapine (NVP). K103N-containing variants were detected more frequently by the ViroSeq HIV-1 Genotyping System in women with subtype C (69.2%) than subtypes A (19.4%, p < 0.0001) or D (36.1%, p < 0.0001). K103N-containing variants were also detected more frequently and at higher levels in women with subtype C by the LigAmp assay. In this report, we analyzed samples collected prior to or within hours after SD NVP administration from antiretroviral drug-naive African women with subtypes A, C, and D. Only 1/254 samples had an NVP resistance mutation detected with the ViroSeq system, and only 4/236 samples had K103N detected at < 0.5% with the LigAmp assay [2/110 (1.8%) with subtype A, 1/46 (2.2%) with subtype C, and 1/80 (1.3%) with subtype D] (p = 0.92). We did not detect significant differences in the pre-NVP frequency of NVP resistance mutations or the pre-NVP levels of K103N-containing variants in women with subtypes A, C, and D that explain the dramatic subtype-based differences in emergence of HIV-1 variants with these mutations after SD NVP exposure.

show abstract

“…In an independent study of 457 RTI-naïve and 1,247 RTI-experienced individuals, I31L, K64H/N/Y, T165L, E203V, R211D, and K223E were observed in five or more RTI-treated but in no RTI-naïve individuals (7). In addition, I31L (25), K64N (25), T165L (25), and K223E (28) were previously reported to possibly be associated with RTI therapy in other studies. Figure 2A shows the locations of the 10 new NRTI positions within the three-dimensional structure of the polymerase coding region of p66 HIV-1 RT.…”

Section: Vol 53 2009 Nonpolymorphic Hiv-1 Protease and Rt Mutationsmentioning

confidence: 99%

Nonpolymorphic Human Immunodeficiency Virus Type 1 Protease and Reverse Transcriptase Treatment-Selected Mutations

Shahriar

Rhee

Liu

et al. 2009

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The spectrum of human immunodeficiency virus type 1 (HIV-1) protease and reverse transcriptase (RT) mutations selected by antiretroviral (ARV) drugs requires ongoing reassessment as ARV treatment patterns evolve and increasing numbers of protease and RT sequences of different viral subtypes are published. Accordingly, we compared the prevalences of protease and RT mutations in HIV-1 group M sequences from individuals with and without a history of previous treatment with protease inhibitors (PIs) or RT inhibitors (RTIs). Mutations in protease sequences from 26,888 individuals and in RT sequences from 25,695 individuals were classified according to whether they were nonpolymorphic in untreated individuals and whether their prevalence increased fivefold with ARV therapy. This analysis showed that 88 PI-selected and 122 RTI-selected nonpolymorphic mutations had a prevalence that was fivefold higher in individuals receiving ARVs than in ARV-naïve individuals. This was an increase of 47% and 77%, respectively, compared with the 60 PI-and 69 RTI-selected mutations identified in a similar analysis that we published in 2005 using subtype B sequences obtained from one-fourth as many individuals. In conclusion, many nonpolymorphic mutations in protease and RT are under ARV selection pressure. The spectrum of treatment-selected mutations is changing as data for more individuals are collected, treatment exposures change, and the number of available sequences from non-subtype B viruses increases.Identifying the mutations responsible for human immunodeficiency virus type 1 (HIV-1) drug resistance has implications for drug resistance surveillance, HIV-1 genotypic resistance testing, and the biophysical mechanisms by which HIV-1 escapes from selective drug pressure. Many mutations in HIV-1 protease and reverse transcriptase (RT) are considered drug resistance mutations by virtue of emerging during antiretroviral (ARV) selection pressure in vitro or in vivo, reducing drug susceptibility in vitro, or reducing the virological response to therapy. As more sequenced HIV-1 isolates from ARV-exposed individuals are reported, more ARVs are licensed, and a greater proportion of published sequences of HIV-1 protease and RT belong to non-B subtypes, it is expected that new treatment-selected mutations will be identified.We previously identified nonpolymorphic treatment-selected mutations in an analysis of subtype B protease and RT sequences from ϳ6,000 individuals in the HIV Drug Resistance Database (HIVDB) (26). Here, we describe the results of a similar analysis that includes non-B group M sequences and about four times as many individuals than in the 2005 study. MATERIALS AND METHODSPatients, viruses, and mutations. HIV-1 RT and protease sequences were compiled from published studies in the HIVDB (http://hivdb.stanford.edu) (27) and from previously unpublished sequences from HIV-1-infected individuals in Northern and Southern California as part of an Institutional Review Boardapproved protocol. For the new virus sequences, treatment his...

show abstract

The K101P and K103R/V179D Mutations in Human Immunodeficiency Virus Type 1 Reverse Transcriptase Confer Resistance to Nonnucleoside Reverse Transcriptase Inhibitors

Cited by 40 publications

References 14 publications

Antiretroviral drug resistance and phylogenetic diversity of HIV‐1 in Chile

Antiretroviral drug resistance and phylogenetic diversity of HIV‐1 in Chile

Short Communication:HIV Type 1 Variants with Nevirapine Resistance Mutations Are Rarely Detected in Antiretroviral Drug-Naive African Women with Subtypes A, C, and D

Nonpolymorphic Human Immunodeficiency Virus Type 1 Protease and Reverse Transcriptase Treatment-Selected Mutations

Contact Info

Product

Resources

About