<!--#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 90I0000 98G10301015 100I45453060 100V30301015 101E15301530 101P60604560 101Q0000 101H15151010 101N0000 103N606000 103R0000 103S456000 103T156000 103Q0000 103E0000 103H606000 106A456000 106M606000 106I0000 108I101500 138A001015 138K10101030 138Q10101015 138G10101015 138R10101015 179D10101010 179E10101010 179T10101010 179L10101015 179I0000 179F10151515 181C30603030 181I30606060 181V30606060 181S15601515 181F15603030 181G15603030 188C606000 188H306000 188L60601560 188F6030030 190A45601515 190S60601515 190E60604545 190Q60604545 190C60601010 190V60601010 190T60601010 221Y10101010 225H303000 227C30303030 227L153000 230L45603045 230I15301530 234I0000 236L0000 238T306000 238N101000 318F103000 348I101500
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
175
B
4120
C
451
D
126
F
82
G
145
AE
333
AG
76
 
A
475
B
7943
C
3272
D
308
F
176
G
429
AE
934
AG
415
179 V I 58
T 0.6
I 3.5
D 0.7
I 2.4
D 0.7
A 0.5
I 5.0
T 0.8
D 0.8
I 5.2 E 4.2
I 0.7
I 12
D 0.9
T 0.6
I 5.4  I 69
T 1.1
I 9.1
D 2.0
E 0.9
D 4.6
I 3.3
E 0.5
I 7.7
D 1.0
I 4.7
D 2.4
T 0.6
L 0.6
E 0.6
E 7.4
I 0.7
I 19
D 3.2
T 1.3
E 0.9
I 5.0
E 3.2
M 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
V179A00529201230.20 
V179A>=105597100.100.512
V179A>=0>=115304150.000.002
V179A>=0NVP404540.000.118
V179A>=0EFV336750.100.421
V179A>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179D00529208111.50 
V179D>=105597410.700.000
V179D>=0>=1153043962.500.000
V179D>=0NVP4045571.400.582
V179D>=0EFV33671845.400.000
V179D>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179E00529202820.50 
V179E>=105597170.300.029
V179E>=0>=1153041691.100.000
V179E>=0NVP4045300.700.104
V179E>=0EFV3367551.600.000
V179E>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179F005292010.00 
V179F>=1055970  
V179F>=0>=115304410.200.000
V179F>=0NVP404520.000.004
V179F>=0EFV336740.100.000
V179F>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179G0052920190.00 
V179G>=10559740.000.357
V179G>=0>=115304250.100.000
V179G>=0NVP404520.001.000
V179G>=0EFV336780.200.000
V179G>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179I005292048179.10 
V179I>=1055973746.600.000
V179I>=0>=115304185612.100.000
V179I>=0NVP404560915.000.000
V179I>=0EFV33672056.000.000
V179I>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179L005292060.00 
V179L>=10559710.000.828
V179L>=0>=115304240.100.000
V179L>=0NVP404540.000.001
V179L>=0EFV336740.100.000
V179L>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179M005292030.00 
V179M>=10559710.000.841
V179M>=0>=115304160.100.000
V179M>=0NVP404560.100.000
V179M>=0EFV336740.100.000
V179M>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179S005292090.00 
V179S>=10559710.000.623
V179S>=0>=11530410.000.573
V179S>=0NVP404510.000.796
V179S>=0EFV33670  
V179S>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V179T00529201460.20 
V179T>=10559790.100.145
V179T>=0>=115304500.300.343
V179T>=0NVP4045170.400.133
V179T>=0EFV336770.200.573
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.