Mutation ARV - Evidence

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MARVEL on RT mutations at position 40

HIVdb Algorithm: Comments & Scores

Mutation	3TC	FTC	ABC	AZT	D4T	DDI	TDF

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 40 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.

Pos	WT	RTI Naive Persons								NRTI (but no NNRTI) Treated Persons
Pos	WT	A 3214	B 22121	C 7684	D 1183	F 678	G 1313	AE 3424	AG 2589	A 172	B 3960	C 288	D 126	F 83	G 142	AE 325	AG 75
40	E	D ¹²	D ^0.8	D ^7.0	D ²⁷ A ^0.6	D ²⁹	D ²⁰	D ^1.3	D ¹¹	D ^9.3		D ^3.4	D ²⁸ F ^0.9 A ^0.9	D ¹⁸	D ^7.4		D ^6.8
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 (+/- NNRTIs). The following rows show the frequency of the mutation in persons who have received only a single NRTI. Mutation rates that differ significantly between treated and untreated isolates are indicated in yellow.

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
E40A	0	0	39267	39	0.00
E40A	>=1	0	5192	2	0.00	0.266
E40A	>=0	>=1	13012	10	0.00	0.575
E40A	AZT	>=0	452	0
E40A	DDI	>=0	53	0
E40A	D4T	>=0	54	0
E40A	ABC	>=0	45	0
E40A	>=0	NVP	3824	5	0.10	0.752
E40A	>=0	EFV	2424	0
E40A	>=0	ETR	0	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
E40D	0	0	39267	2390	6.00
E40D	>=1	0	5192	124	2.30	0.000
E40D	>=0	>=1	13012	503	3.80	0.000
E40D	AZT	>=0	452	24	5.30	0.556
E40D	DDI	>=0	53	1	1.80	0.322
E40D	D4T	>=0	54	3	5.50	0.903
E40D	ABC	>=0	45	1	2.20	0.440
E40D	>=0	NVP	3824	328	8.50	0.000
E40D	>=0	EFV	2424	92	3.70	0.000
E40D	>=0	ETR	0	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
E40F	0	0	39267	0
E40F	>=1	0	5192	16	0.30	0.000
E40F	>=0	>=1	13012	130	0.90	0.000
E40F	AZT	>=0	452	0
E40F	DDI	>=0	53	0
E40F	D4T	>=0	54	0
E40F	ABC	>=0	45	0
E40F	>=0	NVP	3824	8	0.20	0.000
E40F	>=0	EFV	2424	7	0.20	0.000
E40F	>=0	ETR	0	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
E40G	0	0	39267	31	0.00
E40G	>=1	0	5192	3	0.00	0.802
E40G	>=0	>=1	13012	5	0.00	0.182
E40G	AZT	>=0	452	0
E40G	DDI	>=0	53	0
E40G	D4T	>=0	54	0
E40G	ABC	>=0	45	0
E40G	>=0	NVP	3824	0
E40G	>=0	EFV	2424	2	0.00	0.755
E40G	>=0	ETR	0	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
E40K	0	0	39267	31	0.00
E40K	>=1	0	5192	7	0.10	0.297
E40K	>=0	>=1	13012	23	0.10	0.004
E40K	AZT	>=0	452	0
E40K	DDI	>=0	53	0
E40K	D4T	>=0	54	0
E40K	ABC	>=0	45	0
E40K	>=0	NVP	3824	12	0.30	0.000
E40K	>=0	EFV	2424	2	0.00	0.755
E40K	>=0	ETR	0	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
E40Q	0	0	39267	16	0.00
E40Q	>=1	0	5192	5	0.00	0.164
E40Q	>=0	>=1	13012	6	0.00	1.000
E40Q	AZT	>=0	452	0
E40Q	DDI	>=0	53	0
E40Q	D4T	>=0	54	0
E40Q	ABC	>=0	45	0
E40Q	>=0	NVP	3824	3	0.00	0.511
E40Q	>=0	EFV	2424	1	0.00	0.613
E40Q	>=0	ETR	0	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
E40R	0	0	39267	3	0.00
E40R	>=1	0	5192	0
E40R	>=0	>=1	13012	4	0.00	0.124
E40R	AZT	>=0	452	0
E40R	DDI	>=0	53	0
E40R	D4T	>=0	54	0
E40R	ABC	>=0	45	0
E40R	>=0	NVP	3824	0
E40R	>=0	EFV	2424	3	0.10	0.000
E40R	>=0	ETR	0	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
E40V	0	0	39267	6	0.00
E40V	>=1	0	5192	2	0.00	0.533
E40V	>=0	>=1	13012	5	0.00	0.219
E40V	AZT	>=0	452	0
E40V	DDI	>=0	53	0
E40V	D4T	>=0	54	0
E40V	ABC	>=0	45	0
E40V	>=0	NVP	3824	2	0.00	0.326
E40V	>=0	EFV	2424	0
E40V	>=0	ETR	0	0

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 40.

Mutation pattern data is not available for E40.

A complete summary of additional in vitro susceptibility data for viruses with E40 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 23 nonpolymorphic NRTI-resistance mutations shown to contribute decreased susceptibility to at least one NRTI. A complete description of the method that generates this figure can be found at Rhee et al PNAS 2006.

MARVEL on RT mutations at position 40

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