<!--#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 90


HIVdb Algorithm: Comments & Scores
  • V90I is a polymorphic accessory mutation that is weakly selected in patients by each of the NNRTIs. It has a weight of 1.0 in the Tibotec ETR genotypic susceptibility score but is associated with minimal, if any, detectable reduction in NNRTI susceptibility.

MutationEFVNVPETRRPV
V90I0000
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 90 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
90 V I 3.1 I 2.8 I 1.4 I 1.6 I 2.6 I 2.1 I 1.6 I 6.6
G 1.3
 I 3.2 I 3.7 I 3.3 I 4.6 I 4.1 I 4.2 I 4.1 I 12
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
V90A005097070.00 
V90A>=1057520  
V90A>=0>=12084740.000.838
V90AAZT>=04530  
V90ADDI>=0530  
V90AD4T>=0550  
V90AABC>=0470  
V90A>=0NVP430020.000.320
V90A>=0EFV38860  
V90A>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V90G005097090.00 
V90G>=10575230.000.220
V90G>=0>=12084750.000.797
V90GAZT>=04530  
V90GDDI>=0530  
V90GD4T>=0550  
V90GABC>=0470  
V90G>=0NVP430030.000.091
V90G>=0EFV38860  
V90G>=0ETR00  
MutationNRTINNRTINumSeqNumMut% Mutantp
V90I00509709591.80 
V90I>=1057521993.400.000
V90I>=0>=12084711945.700.000
V90IAZT>=0453153.300.040
V90IDDI>=05323.700.612
V90ID4T>=0550  
V90IABC>=04712.100.680
V90I>=0NVP43002505.800.000
V90I>=0EFV38861995.100.000
V90I>=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 90.
Mutation pattern data is not available for V90.

A complete summary of additional in vitro susceptibility data for viruses with V90 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 90.

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.