Mutation ARV - Evidence

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MARVEL on RT mutations at position 151

HIVdb Algorithm: Comments & Scores

Q151M causes intermediate/high-level resistance to AZT, ddI, d4T and ABC and low-level resistance to TDF, 3TC and FTC. In combination with mutations at the associated positions 62, 75, 77, and 116, Q151M confers high-level resistance to AZT, ddI, d4T and ABC and intermediate-level resistance to TDF, 3TC and FTC.
Q151M causes intermediate/high-level resistance to AZT, ddI, d4T and ABC and low-level resistance to TDF, 3TC and FTC. In combination with mutations at the associated positions 75, 77, and 116, Q151M confers high-level resistance to AZT, ddI, d4T and ABC and intermediate-level resistance to TDF, 3TC and FTC. Q151L is an extremely rare transitional mutation that may precede the emergence of the Q151M.

Mutation	3TC	FTC	ABC	AZT	D4T	DDI	TDF 184	I	60	60	15	-10	-10	10	-10 184	V	60	60	15	-10	-10	10	-10 41	L	5	5	10	15	15	10	10 67	N	0	0	5	15	15	5	5 67	E	0	0	5	10	10	5	5 67	G	0	0	5	10	10	5	5 67	STH	0	0	5	10	10	5	5 70	R	0	0	10	30	15	10	10 210	W	5	5	10	15	15	10	10 215	Y	5	5	15	45	45	15	15 215	F	5	5	15	45	45	15	15 219	QENRW	0	0	5	10	10	5	5								40	F	5	5	5	5	5	5	5 44	DA	0	0	0	0	0	0	0 118	I	0	0	0	0	0	0	0								215	CDEIVS	0	0	10	20	20	10	5 215	NAL	0	0	10	20	20	10	5																65	R	30	30	45	-15	45	60	60 65	N	15	15	25	-10	25	25	25 65	E	0	0	10	0	10	10	10 70	GE	10	10	15	-10	15	15	15 70	TSNQ	10	10	10	0	10	10	10 74	I	0	0	30	0	0	60	0 74	V	0	0	30	0	0	60	0 115	F	0	0	45	0	0	0	15																62	V	5	5	5	5	5	5	5 75	I	5	5	5	5	5	5	5 77	L	5	5	10	10	10	10	5 116	Y	5	5	10	10	10	10	5 151	L	10	10	30	30	30	30	10 151	M	15	15	60	60	60	60	15																66	i	30	30	45	45	45	45	45 67	i	30	30	45	45	45	45	45 68	i	30	30	45	45	45	45	45 69	i	30	30	45	45	45	45	45 70	i	30	30	45	45	45	45	45 71	i	30	30	45	45	45	45	45 66	d	15	15	30	30	30	30	30 67	d	15	15	30	30	30	30	30 68	d	15	15	30	30	30	30	30 69	d	15	15	15	0	15	15	15 70	d	15	15	15	0	15	15	15 71	d	15	15	15	0	15	15	15																69	D	0	0	0	0	10	30	0 69	N	0	0	0	5	5	10	0 69	G	0	0	10	0	10	10	5 75	M	0	0	0	10	40	15	0 75	T	0	0	10	0	60	30	0 75	S	0	0	0	0	10	10	0 75	A	0	0	0	0	10	10	0 75	L	0	0	0	0	10	10	0 348	I	0	0	0	10	10	0	0

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 151 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 3547	B 25449	C 8621	D 1320	F 723	G 1577	AE 5645	AG 2906	A 179	B 4133	C 461	D 127	F 82	G 146	AE 339	AG 78
151	Q									M ^1.2	M ^1.6	M ^1.4	M ^0.8		M ^0.7	M ^2.7
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
Q151H	0	0	51719	6	0.00
Q151H	>=1	>=0	21946	6	0.00	0.224
Q151H	AZT	>=0	453	0
Q151H	DDI	>=0	53	0
Q151H	D4T	>=0	55	0
Q151H	ABC	>=0	46	0
Q151H	D4T+3TC	>=0	2998	2	0.00	0.099
Q151H	AZT+3TC	>=0	2277	0
Q151H	D4T+DDI	>=0	462	0
Q151H	AZT+DDI	>=0	577	0
Q151H	ABC+3TC	>=0	230	1	0.40	0.008
Q151H	TDF+3TC	>=0	306	0
Q151H	TDF+FTC	>=0	184	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
Q151K	0	0	51719	8	0.00
Q151K	>=1	>=0	21946	3	0.00	0.882
Q151K	AZT	>=0	453	0
Q151K	DDI	>=0	53	0
Q151K	D4T	>=0	55	0
Q151K	ABC	>=0	46	0
Q151K	D4T+3TC	>=0	2998	5	0.10	0.000
Q151K	AZT+3TC	>=0	2277	3	0.10	0.002
Q151K	D4T+DDI	>=0	462	2	0.40	0.000
Q151K	AZT+DDI	>=0	577	0
Q151K	ABC+3TC	>=0	230	0
Q151K	TDF+3TC	>=0	306	0
Q151K	TDF+FTC	>=0	184	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
Q151L	0	0	51719	2	0.00
Q151L	>=1	>=0	21946	18	0.00	0.000
Q151L	AZT	>=0	453	0
Q151L	DDI	>=0	53	0
Q151L	D4T	>=0	55	0
Q151L	ABC	>=0	46	0
Q151L	D4T+3TC	>=0	2998	5	0.10	0.000
Q151L	AZT+3TC	>=0	2277	3	0.10	0.000
Q151L	D4T+DDI	>=0	462	3	0.60	0.000
Q151L	AZT+DDI	>=0	577	0
Q151L	ABC+3TC	>=0	230	0
Q151L	TDF+3TC	>=0	306	0
Q151L	TDF+FTC	>=0	184	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
Q151M	0	0	51719	0
Q151M	>=1	>=0	21946	665	3.00	0.000
Q151M	AZT	>=0	453	0
Q151M	DDI	>=0	53	0
Q151M	D4T	>=0	55	1	1.80	0.000
Q151M	ABC	>=0	46	0
Q151M	D4T+3TC	>=0	2998	110	3.60	0.000
Q151M	AZT+3TC	>=0	2277	12	0.50	0.000
Q151M	D4T+DDI	>=0	462	26	5.60	0.000
Q151M	AZT+DDI	>=0	577	16	2.70	0.000
Q151M	ABC+3TC	>=0	230	1	0.40	0.000
Q151M	TDF+3TC	>=0	306	3	0.90	0.000
Q151M	TDF+FTC	>=0	184	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
Q151P	0	0	51719	10	0.00
Q151P	>=1	>=0	21946	4	0.00	0.847
Q151P	AZT	>=0	453	0
Q151P	DDI	>=0	53	0
Q151P	D4T	>=0	55	0
Q151P	ABC	>=0	46	0
Q151P	D4T+3TC	>=0	2998	0
Q151P	AZT+3TC	>=0	2277	1	0.00	0.956
Q151P	D4T+DDI	>=0	462	0
Q151P	AZT+DDI	>=0	577	1	0.10	0.274
Q151P	ABC+3TC	>=0	230	0
Q151P	TDF+3TC	>=0	306	0
Q151P	TDF+FTC	>=0	184	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
Q151R	0	0	51719	20	0.00
Q151R	>=1	>=0	21946	10	0.00	0.823
Q151R	AZT	>=0	453	0
Q151R	DDI	>=0	53	0
Q151R	D4T	>=0	55	0
Q151R	ABC	>=0	46	0
Q151R	D4T+3TC	>=0	2998	0
Q151R	AZT+3TC	>=0	2277	0
Q151R	D4T+DDI	>=0	462	0
Q151R	AZT+DDI	>=0	577	0
Q151R	ABC+3TC	>=0	230	0
Q151R	TDF+3TC	>=0	306	0
Q151R	TDF+FTC	>=0	184	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 151.

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 Q151 obtained using other assays including the Antivirogram can be found here. A complete list of all mutation patterns with Q151 (not just the top 10 most frequent patterns) can be found at this page.

Mutation Patterns	Number of Sequences	AZT fold_n	D4T fold_n	TDF fold_n	ABC fold_n	DDI fold_n	3TC fold_n
151M	106	6.7₉	5.4₉	1.0₈	5.2₉	6.4₉	3.0₉
151M,184V	95	126₄	8.1₄	0.8₂	21₃	15₄	200₄
115F,151M,184V	70	584₁	7.2₁	1.6₁	20₁	15₁	200₁
65R,151M	61	52₂	14₂	3.6₂	11₁	15₂	46₂
65R,151M,184V	34
65R,70R,151M	25
65R,115F,151M,184V	24	985₁	25₁	7.5₁		22₁	100₁
115F,151M	16
67N,151M,184V	15	4.6₂	3.5₂	0.3₁	8.5₂	6.4₂	200₂
67N,70R,151M	15	18₁	2.7₁	1.6₁	3.1₁	2.4₁	3.5₁
Footnote: Mutation patterns were defined by the presence or absence of major NRTI 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 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 151

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