<!--#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 190


HIVdb Algorithm: Comments & Scores
  • G190A causes high level resistance to NVP, intermediate resistance to EFV, and increased DLV susceptibility. It has no effect on ETR susceptibility but was associated with a decreased response to ETR in the DUET studies.
  • G190C/T/V are rare mutations that cause high-level resistance to NVP and EFV and increased susceptibility to DLV. Their effect on ETR is not known.
  • G190E/Q cause high-level resistance to NVP and EFV and intermediate resistance to DLV. G190E + Y181C is associated with >100-fold decreased ETR susceptibility.
  • G190E/Q cause high-level resistance to NVP and EFV and intermediate resistance to DLV. G190E + Y181C is associated with >100-fold decreased ETR susceptibility.
  • G190S causes high-level resistance to NVP and EFV and increases DLV susceptibility. Although it was on the list of 13 mutations associated with decreased ETR response in the DUET studies, it does not appear to decrease ETR susceptibility.
  • G190C/T/V are rare mutations that cause high-level resistance to NVP and EFV and increased susceptibility to DLV. Their effect on ETR is not known.
  • G190C/T/V are rare mutations that cause high-level resistance to NVP and EFV and increased susceptibility to DLV. Their effect on ETR is not known.

MutationDLVEFVNVPETR
G190A0406010
G190C0606010
G190E30606010
G190Q30606010
G190S0606010
G190T0606010
G190V0606010
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 190 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
172
B
3960
C
288
D
126
F
83
G
142
AE
325
AG
75
 
A
463
B
8280
C
1994
D
304
F
169
G
428
AE
790
AG
403
190 G A 0.6  A 1.4 A 0.8      A 14
S 2.0 		A 15
S 3.2 		A 11
S 0.7 		A 7.4
S 1.0 		A 6.7
S 2.4 		A 13
S 1.2 		A 23
S 2.2 		A 14
S 0.8
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
G190A00486951130.20 
G190A>=105254210.300.030
G190A>=0>=113071219316.700.000
G190A>=0NVP387869017.700.000
G190A>=0EFV24301947.900.000
G190A>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
G190C004869530.00 
G190C>=1052540  
G190C>=0>=113071160.100.000
G190C>=0NVP38780  
G190C>=0EFV243040.100.000
G190C>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
G190E0048695130.00 
G190E>=1052540  
G190E>=0>=113071510.300.000
G190E>=0NVP387860.100.000
G190E>=0EFV2430210.800.000
G190E>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
G190Q00486950  
G190Q>=1052540  
G190Q>=0>=113071300.200.000
G190Q>=0NVP38780  
G190Q>=0EFV243070.200.000
G190Q>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
G190R0048695190.00 
G190R>=10525430.000.797
G190R>=0>=11307180.000.400
G190R>=0NVP387810.001.000
G190R>=0EFV243030.100.145
G190R>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
G190S0048695140.00 
G190S>=10525420.000.964
G190S>=0>=1130713402.600.000
G190S>=0NVP3878320.800.000
G190S>=0EFV2430843.400.000
G190S>=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 190.
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 G190 obtained using other assays including the Antivirogram can be found here. A complete list of all mutation patterns with G190 (not just the top 10 most frequent patterns) can be found at this page.

Mutation PatternsNumber of
Sequences		NVP
foldn		EFV
foldn		ETR
foldn
181C,190A6892002083214710
190A676120337.1341.18
103N,181C,190A44120052005 
103N,190A44020022002 
101E,181C,190A4092001610117151
101E,190A36320061206 
190S19120014133140.57
103S,190A16020064760.22
101E,190S132200720063.62
101E,181C,190S96   
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.

 

Genotype-clinical outcome correlation
Studies correlating baseline genotype and virological response to an ARV therapy with or without mutations at 190.

ReferencePrevious NNRTIFollow-up NNRTIOther RxNo.PtsWeeksEffect of baseline mutations on response
Madruga(2007)
Katlama (2007), Lazzarin (2007), DUET 		93% had received >= 1 NNRTI. All had >=1 NNRTI resistance mutation at screening or from a historical genotypeETR vs placeboDRV/RTV + OB4062413 baseline mutations were associated with a decreased response to ETR: V90I, A98G, L100I, K101EP, V106I, V179DF, Y181CIV, G190AS. When 3 or more of these mutations were present, the response to ETR was no different from placebo.
Vingerhoets(2008)
DUET follow-up study		93% had received >= 1 NNRTI. All had >=1 NNRTI resistance mutation at screening or from a historical genotypeETR vs placeboDRV/RTV + OB406243 baseline mutations were identified as associated with a decreased VR (defined by RNA <50 copies/ml) at W24: K101H, E138A and V179T in addition to the 13 (V90I, A98G, L100I, K101EP, V106I, V179DF, Y181CIV, G190AS) in Madruga 2007 study. 77% of patients with none of these 16, 61% patients with one of these 16, 56% with two and 38% with >=3 were associated with a decreased VR.
Abbreviations:
    OB - optimized background; VR - virologic response;

References:
  • Madruga J.V., Cahn P., Grinsztejn B., Haubrich R., Lalezari J., Mills A., Pialoux G., Wilkin T., Peeters M., Vingerhoets J., de Smedt G., Leopold L., Trefiglio R., Woodfall B. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet. 2007 Jul 7;370(9581):29-38.
  • Vingerhoets J., Peeters M., Azijn H., Tambuyzer L., Hoogstoel A., Nijs S., de Bethune M-P., Picchio G. An update of the list of NNRTI mutations associated with decreased virological response to etravirine: multivariate analyses on the pooled DUET-1 and DUET-2 clinical trial data [abstract 24]. Antiviral Therapy. 2008; 13 Suppl 3:A26.

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