Mutation ARV - Evidence

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MARVEL on RT mutations at position 68

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 68 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
68	S	G ^1.7	G ^3.7		G ^1.4 N ^0.5	G ^1.4	G ^1.9	G ^6.1	G ^3.8	G ^6.7 N ^0.6	G ^3.6	G ^2.2 R ^0.7	G ^5.7 N ^0.8 C ^0.8 R ^0.8	G ^1.3	G ^2.1 D ^0.7	G ¹²	G ^2.7 N ^1.4 R ^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
S68G	0	0	40212	1276	3.10
S68G	>=1	0	5257	244	4.60	0.000
S68G	>=0	>=1	13085	984	7.50	0.000
S68G	AZT	>=0	452	17	3.70	0.566
S68G	DDI	>=0	53	2	3.70	0.888
S68G	D4T	>=0	55	3	5.40	0.562
S68G	ABC	>=0	45	3	6.60	0.363
S68G	>=0	NVP	3872	301	7.70	0.000
S68G	>=0	EFV	2432	135	5.50	0.000
S68G	>=0	ETR	0	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
S68I	0	0	40212	6	0.00
S68I	>=1	0	5257	2	0.00	0.525
S68I	>=0	>=1	13085	1	0.00	0.847
S68I	AZT	>=0	452	0
S68I	DDI	>=0	53	0
S68I	D4T	>=0	55	0
S68I	ABC	>=0	45	0
S68I	>=0	NVP	3872	0
S68I	>=0	EFV	2432	0
S68I	>=0	ETR	0	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
S68K	0	0	40212	1	0.00
S68K	>=1	0	5257	0
S68K	>=0	>=1	13085	15	0.10	0.000
S68K	AZT	>=0	452	0
S68K	DDI	>=0	53	0
S68K	D4T	>=0	55	0
S68K	ABC	>=0	45	0
S68K	>=0	NVP	3872	2	0.00	0.012
S68K	>=0	EFV	2432	1	0.00	0.239
S68K	>=0	ETR	0	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
S68N	0	0	40212	85	0.20
S68N	>=1	0	5257	12	0.20	0.929
S68N	>=0	>=1	13085	58	0.40	0.000
S68N	AZT	>=0	452	0
S68N	DDI	>=0	53	0
S68N	D4T	>=0	55	0
S68N	ABC	>=0	45	0
S68N	>=0	NVP	3872	17	0.40	0.008
S68N	>=0	EFV	2432	5	0.20	0.867
S68N	>=0	ETR	0	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
S68R	0	0	40212	18	0.00
S68R	>=1	0	5257	9	0.10	0.001
S68R	>=0	>=1	13085	32	0.20	0.000
S68R	AZT	>=0	452	0
S68R	DDI	>=0	53	0
S68R	D4T	>=0	55	0
S68R	ABC	>=0	45	0
S68R	>=0	NVP	3872	3	0.00	0.613
S68R	>=0	EFV	2432	3	0.10	0.220
S68R	>=0	ETR	0	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
S68T	0	0	40212	17	0.00
S68T	>=1	0	5257	2	0.00	0.828
S68T	>=0	>=1	13085	12	0.00	0.059
S68T	AZT	>=0	452	0
S68T	DDI	>=0	53	0
S68T	D4T	>=0	55	0
S68T	ABC	>=0	45	0
S68T	>=0	NVP	3872	1	0.00	0.944
S68T	>=0	EFV	2432	1	0.00	0.630
S68T	>=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 68.

Mutation pattern data is not available for S68.

A complete summary of additional in vitro susceptibility data for viruses with S68 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 68

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