- 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 |
H221Y | 10 | 10 | 10 | 10 |
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 |
A 286 | B 4182 | C 1225 | D 120 | F 80 | G 137 | AE 342 | AG 81 | | A 1796 | B 13827 | C 8296 | D 668 | F 334 | G 994 | AE 2722 | AG 1208 |
221 |
H |
Y 1.1 | Y 0.2 Q 0.1 T 0.1 | Y 0.3 | | Y 1.4 | | D 0.3 | | | Y 7.6 C 0.1 | Y 4.1 C 0.1 L 0.1 | Y 6.5 N 0.1 L 0.1 | Y 6.1 | Y 4.1 | Y 7.0 | Y 9.6 C 0.1 L 0.1 | Y 8.4 I 0.1 |
|
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 | 79335 | 0 | | |
H221C | >=1 | >=0 | 37933 | 27 | 0.00 | 0.000 |
H221C | AZT | >=0 | 436 | 0 | | |
H221C | DDI | >=0 | 54 | 0 | | |
H221C | D4T | >=0 | 53 | 0 | | |
H221C | ABC | >=0 | 7 | 0 | | |
H221C | D4T+3TC | >=0 | 4517 | 2 | 0.00 | 0.000 |
H221C | AZT+3TC | >=0 | 3628 | 7 | 0.10 | 0.000 |
H221C | D4T+DDI | >=0 | 471 | 1 | 0.20 | 0.000 |
H221C | AZT+DDI | >=0 | 694 | 0 | | |
H221C | ABC+3TC | >=0 | 593 | 0 | | |
H221C | TDF+3TC | >=0 | 2502 | 0 | | |
H221C | TDF+FTC | >=0 | 1303 | 0 | | |
Mutation | NRTI | NNRTI | NumSeq | NumMut | % Mutant | p |
H221L | 0 | 0 | 79335 | 12 | 0.00 | |
H221L | >=1 | >=0 | 37933 | 39 | 0.10 | 0.000 |
H221L | AZT | >=0 | 436 | 0 | | |
H221L | DDI | >=0 | 54 | 0 | | |
H221L | D4T | >=0 | 53 | 0 | | |
H221L | ABC | >=0 | 7 | 0 | | |
H221L | D4T+3TC | >=0 | 4517 | 11 | 0.20 | 0.000 |
H221L | AZT+3TC | >=0 | 3628 | 4 | 0.10 | 0.001 |
H221L | D4T+DDI | >=0 | 471 | 2 | 0.40 | 0.000 |
H221L | AZT+DDI | >=0 | 694 | 0 | | |
H221L | ABC+3TC | >=0 | 593 | 0 | | |
H221L | TDF+3TC | >=0 | 2502 | 1 | 0.00 | 0.869 |
H221L | TDF+FTC | >=0 | 1303 | 0 | | |
Mutation | NRTI | NNRTI | NumSeq | NumMut | % Mutant | p |
H221N | 0 | 0 | 79335 | 1 | 0.00 | |
H221N | >=1 | >=0 | 37933 | 9 | 0.00 | 0.000 |
H221N | AZT | >=0 | 436 | 1 | 0.20 | 0.000 |
H221N | DDI | >=0 | 54 | 0 | | |
H221N | D4T | >=0 | 53 | 0 | | |
H221N | ABC | >=0 | 7 | 0 | | |
H221N | D4T+3TC | >=0 | 4517 | 0 | | |
H221N | AZT+3TC | >=0 | 3628 | 0 | | |
H221N | D4T+DDI | >=0 | 471 | 0 | | |
H221N | AZT+DDI | >=0 | 694 | 0 | | |
H221N | ABC+3TC | >=0 | 593 | 0 | | |
H221N | TDF+3TC | >=0 | 2502 | 0 | | |
H221N | TDF+FTC | >=0 | 1303 | 0 | | |
Mutation | NRTI | NNRTI | NumSeq | NumMut | % Mutant | p |
H221P | 0 | 0 | 79335 | 12 | 0.00 | |
H221P | >=1 | >=0 | 37933 | 8 | 0.00 | 0.622 |
H221P | AZT | >=0 | 436 | 0 | | |
H221P | DDI | >=0 | 54 | 0 | | |
H221P | D4T | >=0 | 53 | 0 | | |
H221P | ABC | >=0 | 7 | 0 | | |
H221P | D4T+3TC | >=0 | 4517 | 1 | 0.00 | 0.805 |
H221P | AZT+3TC | >=0 | 3628 | 2 | 0.00 | 0.246 |
H221P | D4T+DDI | >=0 | 471 | 2 | 0.40 | 0.000 |
H221P | AZT+DDI | >=0 | 694 | 1 | 0.10 | 0.247 |
H221P | ABC+3TC | >=0 | 593 | 0 | | |
H221P | TDF+3TC | >=0 | 2502 | 0 | | |
H221P | TDF+FTC | >=0 | 1303 | 0 | | |
Mutation | NRTI | NNRTI | NumSeq | NumMut | % Mutant | p |
H221Q | 0 | 0 | 79335 | 13 | 0.00 | |
H221Q | >=1 | >=0 | 37933 | 8 | 0.00 | 0.741 |
H221Q | AZT | >=0 | 436 | 0 | | |
H221Q | DDI | >=0 | 54 | 0 | | |
H221Q | D4T | >=0 | 53 | 0 | | |
H221Q | ABC | >=0 | 7 | 0 | | |
H221Q | D4T+3TC | >=0 | 4517 | 0 | | |
H221Q | AZT+3TC | >=0 | 3628 | 0 | | |
H221Q | D4T+DDI | >=0 | 471 | 0 | | |
H221Q | AZT+DDI | >=0 | 694 | 0 | | |
H221Q | ABC+3TC | >=0 | 593 | 0 | | |
H221Q | TDF+3TC | >=0 | 2502 | 0 | | |
H221Q | TDF+FTC | >=0 | 1303 | 1 | 0.00 | 0.562 |
Mutation | NRTI | NNRTI | NumSeq | NumMut | % Mutant | p |
H221R | 0 | 0 | 79335 | 19 | 0.00 | |
H221R | >=1 | >=0 | 37933 | 6 | 0.00 | 0.498 |
H221R | AZT | >=0 | 436 | 0 | | |
H221R | DDI | >=0 | 54 | 0 | | |
H221R | D4T | >=0 | 53 | 0 | | |
H221R | ABC | >=0 | 7 | 0 | | |
H221R | D4T+3TC | >=0 | 4517 | 0 | | |
H221R | AZT+3TC | >=0 | 3628 | 2 | 0.00 | 0.535 |
H221R | D4T+DDI | >=0 | 471 | 0 | | |
H221R | AZT+DDI | >=0 | 694 | 0 | | |
H221R | ABC+3TC | >=0 | 593 | 0 | | |
H221R | TDF+3TC | >=0 | 2502 | 1 | 0.00 | 0.885 |
H221R | TDF+FTC | >=0 | 1303 | 0 | | |
Mutation | NRTI | NNRTI | NumSeq | NumMut | % Mutant | p |
H221Y | 0 | 0 | 79335 | 74 | 0.00 | |
H221Y | >=1 | >=0 | 37933 | 2591 | 6.80 | 0.000 |
H221Y | AZT | >=0 | 436 | 0 | | |
H221Y | DDI | >=0 | 54 | 1 | 1.80 | 0.047 |
H221Y | D4T | >=0 | 53 | 1 | 1.80 | 0.044 |
H221Y | ABC | >=0 | 7 | 3 | 42.80 | 0.000 |
H221Y | D4T+3TC | >=0 | 4517 | 426 | 9.40 | 0.000 |
H221Y | AZT+3TC | >=0 | 3628 | 176 | 4.80 | 0.000 |
H221Y | D4T+DDI | >=0 | 471 | 25 | 5.30 | 0.000 |
H221Y | AZT+DDI | >=0 | 694 | 9 | 1.20 | 0.000 |
H221Y | ABC+3TC | >=0 | 593 | 43 | 7.20 | 0.000 |
H221Y | TDF+3TC | >=0 | 2502 | 182 | 7.20 | 0.000 |
H221Y | TDF+FTC | >=0 | 1303 | 72 | 5.50 | 0.000 | 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.
 | 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. | | |