Mutation ARV - Evidence

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MARVEL on RT mutations at position 221

HIVdb Algorithm: Comments & Scores

H221Y is a nonpolymorphic accessory NNRTI-selected mutation that frequently occurs in combination with Y181C. Alone it has minimal detectable effects on NNRTI susceptibility. It is frequently selected in patients receiving RPV (Rimsky 2012, Tibotec 2012).

Mutation	EFV	NVP	ETR	RPV 90	I	0	0	0	0 98	G	10	30	10	15 100	I	45	45	30	60 100	V	30	30	10	15 101	E	15	30	15	30 101	P	60	60	45	60 101	Q	0	0	0	0 101	H	15	15	10	10 101	N	0	0	0	0 103	N	60	60	0	0 103	R	0	0	0	0 103	S	45	60	0	0 103	T	15	60	0	0 103	Q	0	0	0	0 103	E	0	0	0	0 103	H	60	60	0	0 106	A	45	60	0	0 106	M	60	60	0	0 106	I	0	0	0	0 108	I	10	15	0	0 138	A	0	0	10	15 138	K	10	10	10	30 138	Q	10	10	10	15 138	G	10	10	10	15 138	R	10	10	10	15 179	D	10	10	10	10 179	E	10	10	10	10 179	T	10	10	10	10 179	L	10	10	10	15 179	I	0	0	0	0 179	F	10	15	15	15 181	C	30	60	30	30 181	I	30	60	60	60 181	V	30	60	60	60 181	S	15	60	15	15 181	F	15	60	30	30 181	G	15	60	30	30 188	C	60	60	0	0 188	H	30	60	0	0 188	L	60	60	15	60 188	F	60	30	0	30 190	A	45	60	15	15 190	S	60	60	15	15 190	E	60	60	45	45 190	Q	60	60	45	45 190	C	60	60	10	10 190	V	60	60	10	10 190	T	60	60	10	10 221	Y	10	10	10	10 225	H	30	30	0	0 227	C	30	30	30	30 227	L	15	30	0	0 230	L	45	60	30	45 230	I	15	30	15	30 234	I	0	0	0	0 236	L	0	0	0	0 238	T	30	60	0	0 238	N	10	10	0	0 318	F	10	30	0	0 348	I	10	15	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 221 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	NRTI (but no NNRTI) Treated Persons								NNRTI Treated Persons
Pos	WT	A 175	B 4120	C 451	D 126	F 82	G 145	AE 333	AG 76	A 475	B 7943	C 3272	D 308	F 176	G 429	AE 934	AG 415
221	H	Y ^0.6				Y ^1.3				Y ^3.6	Y ^4.8	Y ^4.4	Y ^2.8	Y ^5.4	Y ^7.9	Y ¹²	Y 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.

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
H221C	0	0	44661	0
H221C	>=1	>=0	19467	15	0.00	0.000
H221C	AZT	>=0	417	0
H221C	DDI	>=0	52	0
H221C	D4T	>=0	53	0
H221C	ABC	>=0	4	0
H221C	D4T+3TC	>=0	2936	1	0.00	0.068
H221C	AZT+3TC	>=0	2080	2	0.00	0.000
H221C	D4T+DDI	>=0	456	1	0.20	0.000
H221C	AZT+DDI	>=0	498	0
H221C	ABC+3TC	>=0	226	0
H221C	TDF+3TC	>=0	283	0
H221C	TDF+FTC	>=0	149	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
H221L	0	0	44661	8	0.00
H221L	>=1	>=0	19467	19	0.00	0.000
H221L	AZT	>=0	417	0
H221L	DDI	>=0	52	0
H221L	D4T	>=0	53	0
H221L	ABC	>=0	4	0
H221L	D4T+3TC	>=0	2936	7	0.20	0.000
H221L	AZT+3TC	>=0	2080	2	0.00	0.106
H221L	D4T+DDI	>=0	456	2	0.40	0.000
H221L	AZT+DDI	>=0	498	0
H221L	ABC+3TC	>=0	226	0
H221L	TDF+3TC	>=0	283	0
H221L	TDF+FTC	>=0	149	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
H221P	0	0	44661	10	0.00
H221P	>=1	>=0	19467	5	0.00	0.975
H221P	AZT	>=0	417	0
H221P	DDI	>=0	52	0
H221P	D4T	>=0	53	0
H221P	ABC	>=0	4	0
H221P	D4T+3TC	>=0	2936	1	0.00	0.823
H221P	AZT+3TC	>=0	2080	2	0.00	0.176
H221P	D4T+DDI	>=0	456	2	0.40	0.000
H221P	AZT+DDI	>=0	498	0
H221P	ABC+3TC	>=0	226	0
H221P	TDF+3TC	>=0	283	0
H221P	TDF+FTC	>=0	149	0

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
H221Q	0	0	44661	9	0.00
H221Q	>=1	>=0	19467	3	0.00	0.929
H221Q	AZT	>=0	417	0
H221Q	DDI	>=0	52	0
H221Q	D4T	>=0	53	0
H221Q	ABC	>=0	4	0
H221Q	D4T+3TC	>=0	2936	0
H221Q	AZT+3TC	>=0	2080	0
H221Q	D4T+DDI	>=0	456	0
H221Q	AZT+DDI	>=0	498	0
H221Q	ABC+3TC	>=0	226	0
H221Q	TDF+3TC	>=0	283	0
H221Q	TDF+FTC	>=0	149	1	0.60	0.010

Mutation	NRTI	NNRTI	NumSeq	NumMut	% Mutant	p
H221Y	0	0	44661	33	0.00
H221Y	>=1	>=0	19467	1141	5.80	0.000
H221Y	AZT	>=0	417	0
H221Y	DDI	>=0	52	1	1.90	0.020
H221Y	D4T	>=0	53	1	1.80	0.022
H221Y	ABC	>=0	4	2	50.00	0.000
H221Y	D4T+3TC	>=0	2936	295	10.00	0.000
H221Y	AZT+3TC	>=0	2080	73	3.50	0.000
H221Y	D4T+DDI	>=0	456	25	5.40	0.000
H221Y	AZT+DDI	>=0	498	7	1.40	0.000
H221Y	ABC+3TC	>=0	226	14	6.10	0.000
H221Y	TDF+3TC	>=0	283	17	6.00	0.000
H221Y	TDF+FTC	>=0	149	4	2.60	0.000

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 221.

Mutation pattern data is not available for H221.

A complete summary of additional in vitro susceptibility data for viruses with H221 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.

MARVEL on RT mutations at position 221

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