<!--#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 179


HIVdb Algorithm: Comments & Scores
  • V179D is a polymorphic accessory mutation selected in patients receiving EFV. It reduces NVP and EFV susceptibility by 2 to 5-fold and ETR and RPV susceptibility ~2-fold. The combination of V179D and K103R act synergistically to reduce NVP and EFV susceptibility >10-fold. V179D has a weight of 1.0 in the Tibotec ETR GSS. V179E is a nonpolymorphic mutation infrequently selected by NVP and EFV. V179E appears to be similar to V179D in its effects on NNRTIs.
  • V179F is a nonpolymorphic mutation frequently selected in patients receiving ETR. It nearly always occurs in combination with Y181C. Alone V179F has little effect on NNRTI susceptibility. In combination with Y181C, however, it is associated with high-level ETR and RPV resistance (>10-fold reduced susceptibility). It has a weight of 1.5 in the Tibotec ETR GSS.
  • V179I is a polymorphic mutation that is frequently selected in patients receiving ETR and RPV. It has little, if any, effect on NNRTI susceptibility.
  • V179L is a rare nonpolymorphic mutation infrequently selected in patients receiving NVP, EFV and RPV. Its effects on NNRTI susceptibility have not been well studied. It is listed as an RPV-associated drug-resistance mutation in the RPV package insert.
  • V179T is a rare nonpolymorphic mutation infrequently selected in patients receiving NNRTIs. It is associated with minimal reductions in ETR and RPV susceptibility. It has a weight of 1.0 in the Tibotec ETR GSS.

MutationEFVNVPETRRPV
V179D10101010
V179E10101010
V179F10151515
V179I0000
V179L10101015
V179T10101010
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 179 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
330
AG
78
 
A
635
B
10958
C
3765
D
419
F
275
G
874
AE
1679
AG
824
179 V I 52
T 0.5
I 3.5
D 0.7
I 3.4
A 1.0
D 0.8
I 5.0
T 0.8
D 0.8
I 5.2 E 4.2
I 0.7
I 13
D 1.0
T 0.6
I 5.3  I 62
T 1.1
E 0.5
I 8.7
D 1.8
E 0.8
D 4.9
I 3.6
E 0.5
I 9.8
D 0.7
I 6.5
D 2.3
E 7.1
I 1.4
I 23
D 2.5
E 1.1
T 0.7
I 3.9
E 2.4
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
V179A00591661510.20 
V179A>=105750130.200.777
V179A>=0>=120840170.000.000
V179A>=0NVP432040.000.053
V179A>=0EFV389250.100.169
V179A>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179C005916660.00 
V179C>=10575010.000.874
V179C>=0>=12084040.000.519
V179C>=0NVP432010.000.975
V179C>=0EFV389210.000.916
V179C>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179D00591669571.60 
V179D>=105750440.700.000
V179D>=0>=1208405062.400.000
V179D>=0NVP4320601.300.275
V179D>=0EFV38922255.700.000
V179D>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179E00591663470.50 
V179E>=105750190.300.017
V179E>=0>=1208402481.100.000
V179E>=0NVP4320360.800.055
V179E>=0EFV3892681.700.000
V179E>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179F005916620.00 
V179F>=1057500  
V179F>=0>=120840490.200.000
V179F>=0NVP432020.000.015
V179F>=0EFV389250.100.000
V179F>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179G0059166200.00 
V179G>=10575040.000.323
V179G>=0>=120840290.100.000
V179G>=0NVP432020.001.000
V179G>=0EFV389290.200.000
V179G>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179I005916655369.30 
V179I>=1057503926.800.000
V179I>=0>=120840253712.100.000
V179I>=0NVP432065815.200.000
V179I>=0EFV38922396.100.000
V179I>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179L005916670.00 
V179L>=10575010.000.796
V179L>=0>=120840290.100.000
V179L>=0NVP432040.000.001
V179L>=0EFV389240.100.000
V179L>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179M005916630.00 
V179M>=10575010.000.797
V179M>=0>=120840200.000.000
V179M>=0NVP432060.100.000
V179M>=0EFV389240.100.000
V179M>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179S0059166100.00 
V179S>=10575010.000.615
V179S>=0>=12084030.000.944
V179S>=0NVP432020.000.433
V179S>=0EFV38920  
V179S>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179T00591661530.20 
V179T>=10575090.100.179
V179T>=0>=120840600.200.530
V179T>=0NVP4320190.400.039
V179T>=0EFV389270.100.435
V179T>=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 179.
Mutation pattern data is not available for V179.

A complete summary of additional in vitro susceptibility data for viruses with V179 obtained using other assays including the Antivirogram can be found 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 179.

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.