Table 2.
Amino acid substitutions found in consensus sequences of the protease (A) and reverse transcriptase (B, C) of sequential HIV-1 samples from cases 1 to 3
| A. Protease | ||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Amino acid positiona |
||||||||||||||||||||||||||||
| 10 |
12 |
14 |
15 |
16 |
19 |
32 |
35 |
37 |
38 |
41 |
46 |
57 |
59 |
61 |
62 |
63 |
64 |
65 |
72 |
73 |
77 |
82 |
84 |
90 |
93 |
|||
| Case | Sample | Antiretroviral therapyb | L | T | K | I | G | L | V | E | N | L | R | M | R | Y | Q | I | P | I | E | I | G | V | V | I | L | I |
| 1 | 11.94 | AZT | – | – | (R) | – | – | – | – | – | S | – | K | – | – | – | – | – | L | – | – | – | – | – | – | – | – | – |
| 7.95 | AZT | – | – | – | – | – | – | – | – | S | – | K | – | – | – | – | – | L | – | – | – | – | (L) | – | – | – | – | |
| 12.95 | AZT | – | – | – | – | – | – | – | – | S | – | K | – | – | – | – | – | L | – | – | – | – | – | – | – | – | – | |
| 9.96 | AZT+ddI | – | – | – | – | – | – | – | – | S | – | K | – | – | – | – | – | L | – | – | – | – | – | – | – | – | – | |
| 5.97 | AZT+ddI | – | – | – | – | – | – | – | – | S | – | K | – | – | – | – | – | L | – | – | – | – | – | – | – | – | – | |
| 7.97 | d4T+3TC+RTV | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | L | – | – | – | – | – | – | – | – | – | |
| 3.98 | d4T+3TC+SQV | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | L | – | – | – | – | – | – | – | – | – | |
| 8.98-DNA | d4T+3TC+SQV+NFV | – | – | – | – | – | – | – | – | – | S | – | – | K | – | – | – | L | – | – | – | – | – | – | – | – | – | |
| 2 | 9.95 | AZT+ddI | – | – | – | – | – | – | – | D | – | – | – | – | (K) | – | – | – | – | – | – | V | – | I | – | – | – | L |
| 8.96 | AZT+d4T+3TC | – | – | – | – | – | – | – | D | – | – | – | – | – | – | – | – | – | – | – | V | – | I | – | – | – | L | |
| 10.97 | ddI+d4T+RTV+SQV (stopped) | – | – | – | – | – | – | I | – | – | – | – | I | – | – | – | – | – | – | – | V | – | – | A | – | – | L | |
| 1.98 | ddI+d4T+RTV+SQV | I | – | – | – | – | – | – | D | – | – | – | I | – | – | – | V | – | – | – | V | S | I | – | V | M | L | |
| 8.98 | d4T+3TC+NVP+RTV+SQV | – | – | – | – | – | – | I | – | – | – | – | I | – | – | – | – | – | – | – | – | – | – | A | – | – | L | |
| 9.98 | d4T+3TC+NVP+RTV+SQV (b.c.) | I | – | – | – | – | – | – | D | – | – | – | I | – | – | – | V | – | – | – | V | S | – | – | V | M | L | |
| 1.99 | ddI+d4T+NVP+RTV+NFV+HU | I | – | – | – | – | – | – | D | – | – | – | I | – | – | – | V | – | – | – | V | S | – | – | V | M | L | |
| 3 | 1 (2.94) | AZT+ddC | – | – | – | – | E | – | – | – | – | – | – | – | – | – | – | V | E | L | – | – | – | I | – | – | – | – |
| 2 (1.95) | AZT+ddC | – | – | – | – | E | V | – | – | – | – | – | – | – | – | (K) | V | C | – | – | – | – | I | – | – | – | – | |
| 3 (6.95) | ddI | – | – | – | (L) | E | – | – | – | – | (P) | – | – | – | – | E | V | Q | – | – | – | – | I | – | – | – | – | |
| 4 (8.95) | AZT+3TC | – | K | – | (V) | E | – | – | – | – | – | – | – | K | – | E | V | Q | – | D | – | – | I | – | – | – | – | |
| 5 (9.95) | AZT+3TC | – | – | – | – | E | – | – | – | – | – | – | – | – | – | N,D | V | Q,H | – | (D) | – | – | I | – | – | – | – | |
| 6 (5.96) | AZT+3TC | – | – | – | – | E | – | – | – | – | (P) | – | – | – | (S) | – | V | Q | – | – | (V) | – | I | – | – | – | – | |
| B. Reverse transcriptase (aa 1–120) | ||||||||||||||||||||||||||||
|
Amino acid position (1–120)a |
||||||||||||||||||||||||||||
| 20 | 41 | 46 | 49 | 53 | 54 | 57 | 61 | 67 | 68 | 69 | ins. | 70 | 72 | 83 | 88 | 90 | 100 | 102 | 103 | 106 | 109 | 118 | ||||||
| Case | Sample | Antiretroviral therapyb | K | M | K | K | E | N | N | F | D | S | T | – | K | R | R | W | V | L | K | K | V | L | V | |||
| 1 | 11.94 | AZT | – | – | – | R | – | – | – | S | – | – | – | – | – | – | – | – | I | – | R | – | – | – | – | |||
| 7.95 | AZT | – | – | – | – | – | – | – | – | – | – | – | – | R | – | – | – | – | – | – | – | – | – | – | ||||
| 12.95 | AZT | – | – | – | – | – | – | – | – | – | – | – | – | R | – | – | – | – | – | – | – | – | – | – | ||||
| 9.96 | AZT+ddI | – | – | – | – | – | – | – | – | N | – | – | – | R | (G) | – | – | – | (V) | – | – | (L) | (R) | – | ||||
| 5.97 | AZT+ddI | (R) | L | – | – | – | – | – | – | – | – | S | SS | R | – | – | – | – | – | – | – | – | – | (F) | ||||
| 7.97 | d4T+3TC+RTV | – | – | – | R | – | (K) | – | – | – | – | – | – | – | – | – | – | I | – | (R) | – | – | – | – | ||||
| 3.98 | d4T+3TC+SQV | – | – | – | R | – | – | – | – | – | – | – | – | – | – | – | – | I | – | – | – | – | – | – | ||||
| 8.98-DNA | d4T+3TC+SQV+NFV | – | – | – | – | – | – | – | – | – | – | – | – | (R) | – | – | – | – | – | – | – | – | – | – | ||||
| 2 | 9.95 | AZT+ddI | – | – | – | – | – | – | – | – | N | – | – | – | R | – | – | – | – | – | – | – | – | – | – | |||
| 8.96 | AZT+d4T+3TC | – | – | – | – | – | – | – | – | N | – | – | – | R | – | – | – | – | – | – | – | – | – | – | ||||
| 10.97 | ddI+d4T+RTV+SQV (stopped) | – | – | – | – | – | – | – | – | N | – | D | – | R | – | – | – | – | – | – | – | – | – | – | ||||
| 1.98 | ddI+d4T+RTV+SQV | – | L | – | – | – | – | – | – | N | – | D | – | – | – | – | – | – | – | – | – | – | – | – | ||||
| 8.98 | d4T+3TC+NVP+RTV+SQV | – | – | – | – | – | – | – | – | N | – | D | – | R | – | – | – | – | – | – | – | – | – | – | ||||
| 9.98 | d4T+3TC+NVP+RTV+SQV (b.c.) | – | L | – | – | – | – | S | – | N | – | D | – | – | – | – | – | – | – | – | N | – | – | I | ||||
| 1.99 | ddI+d4T+NVP+RTV+NFV+HU | – | L | – | – | – | – | – | – | N | – | D | – | – | – | – | – | – | – | – | – | – | – | I | ||||
| 3 | 1 (2.94) | AZT+ddC | – | L | – | – | – | – | – | – | – | – | S | SS | – | – | K | – | – | – | – | – | – | – | – | |||
| 2 (1.95) | AZT+ddC | – | L | (E) | – | (G) | – | – | (S) | – | – | S | SS | – | – | K | S | – | – | – | – | – | – | – | ||||
| 3 (6.95) | ddI | – | L | – | – | – | – | – | (S) | – | – | S | – | – | – | K | – | – | – | – | – | – | – | – | ||||
| 4 (8.95) | AZT+3TC | – | L | – | – | – | – | – | – | – | (N) | S | SG | – | – | – | S | – | – | – | – | – | – | – | ||||
| 5 (9.95) | AZT+3TC | – | L | – | – | – | – | – | – | – | – | S | SG | – | – | – | S | – | – | – | – | – | – | – | ||||
| 6 (5.96) | AZT+3TC | – | L | – | – | – | – | – | – | – | – | S | SG | – | – | – | S | – | – | – | – | – | – | – | ||||
| C. Reverse transcriptase (aa 121–220) | ||||||||||||||||||||||||||||
|
Amino acid position (121–220)a |
||||||||||||||||||||||||||||
| 122 | 123 | 125 | 127 | 135 | 162 | 163 | 166 | 169 | 177 | 178 | 184 | 186 | 188 | 196 | 202 | 210 | 211 | 214 | 215 | |||||||||
| Case | Sample | Antiretroviral therapyb | K | D | R | Y | T | S | S | K | E | D | I | M | D | Y | G | I | L | R | L | T | ||||||
| 1 | 11.94 | AZT | – | – | – | – | I | – | – | – | D | – | – | – | – | – | – | – | – | K | F | – | ||||||
| 7.95 | AZT | E | N | – | – | I | – | – | – | D | – | – | – | – | – | – | – | – | K | F | – | |||||||
| 12.95 | AZT | – | – | – | – | I | (C) | – | – | D | – | – | – | – | – | – | – | – | – | F | Y | |||||||
| 9.96 | AZT+ddI | – | – | – | (F) | V | C | – | – | – | (E) | (M) | – | – | – | – | – | – | – | F | Y | |||||||
| 5.97 | AZT+ddI | – | – | (K) | – | V | C | (T) | – | – | (E) | (M) | – | – | – | – | – | – | – | F | Y | |||||||
| 7.97 | d4T+3TC+RTV | – | – | – | – | I | – | – | – | – | – | – | – | – | – | – | – | – | K | F | – | |||||||
| 3.98 | d4T+3TC+SQV | – | – | – | – | I | – | – | – | D | – | – | – | – | – | – | – | – | K | F | – | |||||||
| 8.98-DNA | d4T+3TC+SQV+NFV | – | – | – | – | I | C | – | – | – | – | – | – | – | – | – | – | – | – | F | – | |||||||
| 2 | 9.95 | AZT+ddI | – | – | – | – | I | – | – | – | – | – | – | – | – | – | – | – | – | K | F | Y | ||||||
| 8.96 | AZT+d4T+3TC | – | – | – | – | I | – | – | – | – | – | – | (V) | – | – | – | – | – | K | F | Y | |||||||
| 10.97 | ddI+d4T+RTV+SQV (stopped) | E | – | – | – | I | – | – | – | – | – | – | V | – | – | – | – | – | K | F | Y | |||||||
| 1.98 | ddI+d4T+RTV+SQV | – | – | – | – | I | – | – | – | – | – | – | – | – | – | – | – | W | K | F | Y | |||||||
| 8.98 | d4T+3TC+NVP+RTV+SQV | E | – | – | – | I | – | – | – | – | – | – | V | – | – | – | – | – | K | F | Y | |||||||
| 9.98 | d4T+3TC+NVP+RTV+SQV (b.c.) | – | – | – | – | I | – | – | – | – | – | – | V | – | – | – | – | W | K | F | Y | |||||||
| 1.99 | ddI+d4T+NVP+RTV+NFV+HU | – | – | – | – | I | – | – | – | – | – | – | – | – | L | – | – | W | K | F | Y | |||||||
| 3 | 1 (2.94) | AZT+ddC | – | – | – | F | I | – | – | R | – | N | – | – | – | – | E | – | – | – | F | Y | ||||||
| 2 (1.95) | AZT+ddC | – | – | – | F | I | – | – | R | – | – | – | – | Y | – | E | V | – | – | F | Y | |||||||
| 3 (6.95) | ddI | – | – | – | F | I | – | – | R | – | – | – | – | – | – | E | – | – | – | F | Y | |||||||
| 4 (8.95) | AZT+3TC | – | – | – | – | I | – | – | R | – | E | – | – | – | – | E | – | – | – | F | Y | |||||||
| 5 (9.95) | AZT+3TC | – | – | – | F | I | – | – | R | – | E | – | – | – | – | E | – | – | – | F | Y | |||||||
| 6 (5.96) | AZT+3TC | – | – | – | F | I | – | – | R | – | E | – | – | – | – | E | – | – | – | F | Y | |||||||
Sample identification, treatment history and clinical events of the patients are summarized in Table 1.
a
The single letter amino acid (aa) code is used. Dash means no change relative to the reference HIV-1 sequence shown at the top (HIV-1 CAM-1 strain, GenBank accession number D10112).50 Amino acids in parenthesis indicate that the residue is found in a mixture with the amino acid of the reference sequence shown at the top in a proportion of about 50% (range 40–60% according to the sequence peak pattern). Data from cases 1 and 3 are adapted from Briones et al.51 Amino acid substitutions at positions relevant to resistance to PRI or RTI have been highlighted with bold-face letters.29., 30.
b
Current therapy at the sampling date is indicated. Abbreviation: b.c., bad compliance. Dates of antiretroviral therapy introduction and drugs abbreviations are shown in Table 1.