<!--#if expr="$title" --> <!--#echo var="title" --> <!--#else --> HIV Drug Resistance Database <!--#endif -->
Stanford University HIV Drug Resistance Database - A curated public database designed to represent, store, and analyze the divergent forms of data underlying HIV drug resistance.

MARVEL on RT mutations at position 103


HIVdb Algorithm: Comments & Scores
  • K103E/Q are rare mutations that have not been associated with reduced susceptibility to the current NNRTIs.
  • K103H is a rare nonpolymorphic mutation that causes high-level resistance (~20-fold reduction in susceptibility) to NVP and EFV.
  • K103N is a nonpolymorphic mutation that causes high-level resistance to NVP (~50-fold reduced susceptibility) and EFV (~20-fold reduced susceptibility).
  • K103R is a polymorphic mutation that by alone has no effect on NNRTI susceptibility. However, in combination with V179D (and possibly V179E), it reduces NVP and EFV susceptibility about 15-fold.
  • K103S is a nonpolymorphic mutation that causes intermediate/high-level resistance to NVP and low/intermediate-level resistance to EFV. Because K103S is a 2-bp change from the wildtype K, patients with K103S may be more likely to harbor K103N (which is just a 1-bp change from wildtype).
  • K103T is an extremely rare nonpolymorphic mutation that appears to cause intermediate/high-level resistance to NVP (~10-fold reduction in susceptibility), but it has little if any effect on EFV susceptibility.

MutationEFVNVPETRRPV
K103E0000
K103H606000
K103N606000
K103Q0000
K103R0000
K103S456000
K103T156000
Footnote:Mutation scores on the left are derived from published literature linking mutations and ARVs (the complete details can be found in the HIVdb Release Notes).
Genotype-treatment correlation
Mutation frequency according to subtype and drug-class experience.
The frequency of each mutation at position 103 according to subtype and drug-class experience. Data are shown for the 8 most common subtypes. The number of persons in each subtype/treatment category is shown beneath the subtype. Mutations occurring at a frequency >0.5% are shown. Each mutation is also a hyper-link to a separate web page with information on each isolate, including literature references with PubMed abstracts, the GenBank accession number, and complete sequence and treatment records.

PosWTNRTI (but no NNRTI) Treated Persons NNRTI Treated Persons
A
205
B
4133
C
551
D
127
F
82
G
146
AE
325
AG
78
 
A
635
B
10956
C
3765
D
418
F
275
G
874
AE
1636
AG
823
103 K N 2.0 R 2.0 N 2.2
R 0.7
N 1.6
R 0.8
N 2.4
R 1.2
Q 0.7
N 0.7
 R 1.3  N 19
S 1.0
R 0.7
N 34
R 1.8
S 1.3
N 37
R 3.0
S 1.5
N 19
R 0.5
N 32
R 1.5
S 0.7
N 37
S 0.5
R 0.5
N 26
R 1.3
S 0.8
N 32
S 0.6
Footnote: The query page Mutation Prevalence According to Subtype and Treatment to examine the frequency of all mutations according to subtype and treatment; The program HIVSeq provides similar output for mutations in user-submitted sequences; A complete description of the program that generates these tables can be found at Rhee et al AIDS 2006.
 

Mutation frequency according to treatment with individual ARVs.
The first row shows the frequency of the mutation in persons who are RTI-naive (indicated in green). The second row shows the frequency of the mutation in persons who have received one or more NRTIs (No NNRTIs). The third row shows the frequency of the mutation in persons who have received one or more NNRTIs (+/- NRTIs). The following rows show the frequency of the mutation in persons who have received only a single NNRTI. Mutation rates that differ significantly between treated and untreated isolates are indicated in yellow.
MutationNRTINNRTINumSeqNumMut% Mutantp
K103E0057711270.00 
K103E>=1057510  
K103E>=0>=120795100.000.909
K103E>=0NVP428930.000.760
K103E>=0EFV388430.000.648
K103E>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
K103H00577110  
K103H>=1057510  
K103H>=0>=120795220.100.000
K103H>=0NVP428910.000.090
K103H>=0EFV38840  
K103H>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
K103N00577117411.20 
K103N>=105751801.300.533
K103N>=0>=120795732335.200.000
K103N>=0NVP4289126429.400.000
K103N>=0EFV3884198050.900.000
K103N>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
K103Q0057711430.00 
K103Q>=10575150.000.938
K103Q>=0>=120795120.000.527
K103Q>=0NVP428940.000.888
K103Q>=0EFV388420.000.836
K103Q>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
K103R005771111642.00 
K103R>=1057511131.900.827
K103R>=0>=1207954522.100.182
K103R>=0NVP4289501.100.000
K103R>=0EFV38841473.700.000
K103R>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
K103S0057711180.00 
K103S>=10575140.000.263
K103S>=0>=1207952251.000.000
K103S>=0NVP4289380.800.000
K103S>=0EFV3884340.800.000
K103S>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
K103T0057711120.00 
K103T>=10575140.000.074
K103T>=0>=120795160.000.001
K103T>=0NVP428990.200.000
K103T>=0EFV38840  
K103T>=0ETR00  
Footnote: About one-half of the untreated isolates belong to non-subtype B isolates; About 20% of the treated isolates belong to non-subtype B isolates; A page containing summaries for all of the mutations at this position can be found here.

Genotype-phenotype correlation
Phenotypes of top 10 common patterns of drug resistance mutations with mutations at position 103.
Mutation patterns are listed in the frequency with which they have been reported in the published literature. The median level of fold resistance (compared with wildtype) for viruses with the mutation pattern in the first column are indicated when available. The subscripts indicate the number of viruses that were phenotyped. The drug susceptibility assay used was the PhenoSense assay (Monogram, South San Francisco). A hyperlink for each individual pattern is provided to access a complete list of mutations and fold resistances for each sequence matching the pattern of mutation.

A complete summary of additional in vitro susceptibility data for viruses with K103 obtained using other assays including the Antivirogram can be found here. A complete list of all mutation patterns with K103 (not just the top 10 most frequent patterns) can be found at this page.

Mutation PatternsNumber of
Sequences
NVP
foldn
EFV
foldn
ETR
foldn
103N731451222212210.957
103N,181C15932005729596.811
100I,103N11487162200596.825
103N,190A51720022002 
103N,181C,190A486200820085.52
103N,230L24620011200113.85
103N,106M21920012001 
101P,103N2052001520015389
103S,190A18920078570.22
103N,188L179200920092.66
Footnote: Mutation patterns were defined by the presence or absence of major NNRTI drug resistance mutations ; Sequences containing a mixture at a major drug resistance positions were excluded; For the cutoffs defined by PhenoSense, open the sample report form provided on this page; The full list of all mutation patterns are also available here.

 

Phenotypic coefficients using machine learning
Least Square Regression (LSR) was used to learn the relative contribution of each mutation to the fold decrease in susceptibility for an ARV. The figure on the left (click to enlarge the figure) shows the regression coefficients (which correlate with the contribution to resistance) for the 24 nonpolymorphic NNRTI-resistance mutations shown to contribute decreased susceptibility to at least one NNRTI. A complete description of the method that generates this figure can be found at Rhee et al PNAS 2006.