<!--#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 188


HIVdb Algorithm: Comments & Scores
  • Y188C is a nonpolymorphic mutation selected in patients receiving NVP and EFV. It confers high-level resistance to NVP (>50-fold reduced susceptibility) and EFV (~20-fold reduced susceptibility).
  • Y188F is a rare nonpolymorphic NNRTI-associated mutations that is usually present as part of an electrophoretic mixture. It appears to represent a transitional mutation between Y and L.
  • Y188H is a nonpolymorphic mutation selected in patients receiving NVP and EFV. It causes about 5 to 10-fold reduced susceptibility to NVP and EFV.
  • Y188L is a nonpolymorphic mutation that causes high-level resistance (>50-fold reduced susceptibility) to NVP and EFV and intermediate/high-level resistance (5-fold reduced susceptibility) to RPV.

MutationEFVNVPETRRPV
Y188C606000
Y188F6030030
Y188H306000
Y188L60601560
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 188 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
188 Y L 0.5  L 0.7       L 1.9 L 4.4 L 4.6
C 1.5
H 0.7
L 1.7
C 0.5
L 2.5 L 4.0 L 5.4 L 4.4
H 0.5
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
Y188C0057714100.00 
Y188C>=10574810.000.602
Y188C>=0>=1207561800.800.000
Y188C>=0NVP4287892.000.000
Y188C>=0EFV3866641.600.000
Y188C>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
Y188D005771480.00 
Y188D>=10574830.000.114
Y188D>=0>=12075630.000.780
Y188D>=0NVP42870  
Y188D>=0EFV386610.000.929
Y188D>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
Y188F005771490.00 
Y188F>=10574820.000.597
Y188F>=0>=120756180.000.000
Y188F>=0NVP428720.000.380
Y188F>=0EFV386650.100.000
Y188F>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
Y188H0057714200.00 
Y188H>=10574810.000.760
Y188H>=0>=120756860.400.000
Y188H>=0NVP428780.100.000
Y188H>=0EFV3866441.100.000
Y188H>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
Y188L0057714550.00 
Y188L>=10574880.100.431
Y188L>=0>=1207568774.200.000
Y188L>=0NVP42871182.700.000
Y188L>=0EFV38662215.700.000
Y188L>=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 188.
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 Y188 obtained using other assays including the Antivirogram can be found here. A complete list of all mutation patterns with Y188 (not just the top 10 most frequent patterns) can be found at this page.

Mutation PatternsNumber of
Sequences
NVP
foldn
EFV
foldn
ETR
foldn
188L9402004376451.715
103N,188L179200920092.66
106M,188C58   
103N,188H56200320030.21
188C5419954450.92
103N,188C53   
188L,190A40   
106M,188L40   
181C,188L392002962221
188H383.617.31 
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.