Mutation ARV - Evidence

HOME Genotype-Rx Genotype-Pheno Genotype-Clinical hivdb program

MARVEL on RT mutations at position 75

HIVdb Algorithm: Comments & Scores

V75T/M/A/S reduce d4T and possibly ddI susceptibility.
V75I increases multinucleoside resistance caused by Q151M when present with F77L and F116Y; its effect in the absence of Q151M is not known.
V75L does not appear to be associated with reduced NRTI susceptibility.
V75T/M/A/S reduce d4T and possibly ddI susceptibility.
V75T/M/A/S reduce d4T and possibly ddI susceptibility.
V75T/M/A/S reduce d4T and possibly ddI susceptibility.

Mutation	3TC	FTC	ABC	AZT	D4T	DDI	TDF
V75A	0	0	5	5	15	10	5
V75I	5	5	5	5	10	10	5
V75L	0	0	2	2	2	2	2
V75M	0	0	5	5	30	20	5
V75S	0	0	5	5	20	10	0
V75T	0	0	5	5	50	20	5

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 75 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 3215	B 22174	C 7465	D 1180	F 684	G 1316	AE 3654	AG 2607	A 172	B 4055	C 303	D 126	F 99	G 142	AE 325	AG 75
75	V				I ^1.0					I ^1.2 T ^0.6	I ^1.2 M ^1.0 T ^0.8	I ^1.4 T ^0.7	T ^0.8 M ^0.8 I ^0.8	M ^1.1	A ^0.7 M ^0.7 I ^0.7	T ^2.2 M ^2.2 I ^1.6	T ^1.4
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 (+/- 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
V75A	0	0	43840	10	0.00
V75A	>=1	>=0	17295	89	0.50	0.000
V75A	AZT	>=0	452	0
V75A	DDI	>=0	53	0
V75A	D4T	>=0	55	0
V75A	ABC	>=0	44	0
V75A	D4T+3TC	>=0	2274	8	0.30	0.000
V75A	AZT+3TC	>=0	2101	2	0.00	0.189
V75A	D4T+DDI	>=0	459	9	1.90	0.000
V75A	AZT+DDI	>=0	511	1	0.10	0.292
V75A	ABC+3TC	>=0	26	0
V75A	TDF+3TC	>=0	94	0
V75A	TDF+FTC	>=0	24	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
V75I	0	0	43840	19	0.00
V75I	>=1	>=0	17295	496	2.80	0.000
V75I	AZT	>=0	452	3	0.60	0.000
V75I	DDI	>=0	53	0
V75I	D4T	>=0	55	1	1.80	0.003
V75I	ABC	>=0	44	2	4.50	0.000
V75I	D4T+3TC	>=0	2274	104	4.50	0.000
V75I	AZT+3TC	>=0	2101	17	0.80	0.000
V75I	D4T+DDI	>=0	459	15	3.20	0.000
V75I	AZT+DDI	>=0	511	14	2.70	0.000
V75I	ABC+3TC	>=0	26	0
V75I	TDF+3TC	>=0	94	3	3.10	0.000
V75I	TDF+FTC	>=0	24	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
V75L	0	0	43840	94	0.20
V75L	>=1	>=0	17295	78	0.40	0.000
V75L	AZT	>=0	452	1	0.20	0.632
V75L	DDI	>=0	53	0
V75L	D4T	>=0	55	0
V75L	ABC	>=0	44	0
V75L	D4T+3TC	>=0	2274	4	0.10	0.877
V75L	AZT+3TC	>=0	2101	4	0.10	1.000
V75L	D4T+DDI	>=0	459	1	0.20	0.623
V75L	AZT+DDI	>=0	511	4	0.70	0.025
V75L	ABC+3TC	>=0	26	0
V75L	TDF+3TC	>=0	94	0
V75L	TDF+FTC	>=0	24	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
V75M	0	0	43840	18	0.00
V75M	>=1	>=0	17295	570	3.20	0.000
V75M	AZT	>=0	452	0
V75M	DDI	>=0	53	0
V75M	D4T	>=0	55	0
V75M	ABC	>=0	44	0
V75M	D4T+3TC	>=0	2274	60	2.60	0.000
V75M	AZT+3TC	>=0	2101	28	1.30	0.000
V75M	D4T+DDI	>=0	459	2	0.40	0.004
V75M	AZT+DDI	>=0	511	5	0.90	0.000
V75M	ABC+3TC	>=0	26	0
V75M	TDF+3TC	>=0	94	1	1.00	0.023
V75M	TDF+FTC	>=0	24	1	4.10	0.000

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
V75S	0	0	43840	1	0.00
V75S	>=1	>=0	17295	45	0.20	0.000
V75S	AZT	>=0	452	0
V75S	DDI	>=0	53	0
V75S	D4T	>=0	55	0
V75S	ABC	>=0	44	0
V75S	D4T+3TC	>=0	2274	11	0.40	0.000
V75S	AZT+3TC	>=0	2101	1	0.00	0.167
V75S	D4T+DDI	>=0	459	0
V75S	AZT+DDI	>=0	511	0
V75S	ABC+3TC	>=0	26	0
V75S	TDF+3TC	>=0	94	0
V75S	TDF+FTC	>=0	24	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
V75T	0	0	43840	0
V75T	>=1	>=0	17295	261	1.50	0.000
V75T	AZT	>=0	452	0
V75T	DDI	>=0	53	2	3.70	0.000
V75T	D4T	>=0	55	1	1.80	0.000
V75T	ABC	>=0	44	0
V75T	D4T+3TC	>=0	2274	26	1.10	0.000
V75T	AZT+3TC	>=0	2101	2	0.00	0.000
V75T	D4T+DDI	>=0	459	23	5.00	0.000
V75T	AZT+DDI	>=0	511	2	0.30	0.000
V75T	ABC+3TC	>=0	26	0
V75T	TDF+3TC	>=0	94	0
V75T	TDF+FTC	>=0	24	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 75.

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 V75 obtained using other assays including the Antivirogram can be found here. A complete list of all mutation patterns with V75 (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
41L,67N,75M,184V,210W,215Y	103	29₆	2.6₆	1.5₄	6.4₆	2.4₆	200₆
41L,67N,75M,210W,215Y	62	241₇	4.0₇	2.6₃	3.8₅	1.8₇	7.0₇
41L,75M,184V,210W,215Y	58	432₂	5.8₂	3.3₂	9.4₂	2.4₂	101₂
41L,67N,69D,75M,184V,210W,215Y	46	38₃	3.6₃	1.9₃	8.6₂	2.5₃	151₂
41L,67N,70R,75M,184V,210W,215Y	31
75M,184V	30
41L,67N,69D,75M,210W,215Y	27	343₃	3.4₃	3.8₃	11₁	1.6₃	5.5₃
75M	26	1.0₁	0.6₁	0.7₁	0.8₁	0.8₁	0.7₁
75T	24	0.5₃	1.4₃	0.9₂	1.6₂	1.4₃	1.9₃
41L,67N,74I,75T,184V,210W,215Y	23	7.0₁	3.4₁	1.0₁	14₁	4.0₁	200₁
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 75

Database

Resources

Team