Table 1.
Protease inhibitor (PI) history, protease mutations and PI susceptibilities of nine pan-PI-resistant HIV-1 isolates
| Sample | VL | CD4 | PIs (years) | PIs (number) | PIsa | Mutations detected by direct PCR Sanger sequencingb | RC (%) | ATV c | FPV | IDV | LPV | NFV | SQV | TPV | DRV |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1456 | 4.5 | 173 | 9 | 6 | SQV, NFV, IDV/r, APV/r, TPV/r, LPV/r | 10I/V, 32I, 33F, 35D, 36M/I, 37S, 46I, 47V, 53F/L, 54L, 55R, 63P, 64V, 66V, 71V, 73T, 79P/A, 84V, 90M, 93I/L | 9 | 98 | 120 | 24 | 140 | 65 | 58 | 3.3 | NA |
| 1459 | 4.5 | 255 | 8 | 5 | IDV, NFV, SQV/r, APV/r, LPV/r | 10I, 13V, 19I, 32I, 33F, 46I, 47V, 54M, 64V, 71V, 73C, 77I, 84V, 90M, 95L | 2 | 38 | 15 | 25 | 85 | 50 | 9.4 | 6.3 | 142 |
| 1556 | 5.7 | 12 | 9 | 7 | IDV, NFV, SQV/r, APV/r, LPV/r, TPV/r, DRV/r | 10F, 11I, 12P, 13V, 15V, 19P, 20T, 32I, 33F, 35G, 36I, 54I/V, 62V, 63P, 70T, 71I, 73S, 79A, 84V, 89V, 90M | 52 | 172 | 108 | 27 | 62 | 83 | 41 | 9.8 | 134 |
| 4736 | 4.7 | 208 | 12 | ≥3 | IDV, LPV/r, TPV/r | 10V, 11I, 13V, 14R, 15V, 20T, 32I, 33F, 36I, 41K, 46L, 54L, 57K, 60E, 63P, 68E, 70T, 71I, 72I/M, 73S, 84V, 89V, 90M, 93L | 13 | 109 | >200 | 21 | 87 | 94 | 93 | 7 | 239 |
| 6585 | 4.7 | 41 | 3.5 | 5 | IDV, SQV/r, NFV APV/r, LPV/r | 10V, 12V/D, 13V, 15V, 20M, 32I, 33F, 43T, 46I, 47V, 54M, 60E, 61D, 62V, 63P, 67Y, 69K, 71I, 72L, 73S, 77I, 82A, 89V, 90M | 96 | 88 | >200 | 88 | >200 | 76 | 12 | 12 | 112 |
| 7118 | 5.1 | 105 | 7.5 | 5 | SQV/r, LPV/r, LPV/r + APV, ATV/r, DRV/r | 10F, 11V/I, 13V, 16A, 19L/V, 33F, 34Q, 43I, 46L, 51A, 54M, 63P, 64M, 71V, 72M, 73A, 84V, 90M | NA | 111 | >200 | 47 | >200 | 51 | >200 | 9.5 | 140 |
| 7859 | 4.5 | 162 | 11 | 5 | NFV, IDV, APV, LPV/r, ATV/r | 10I, 13V, 15V/I, 19I/L, 20A, 32I, 33F, 36I, 46I, 47V, 54M, 63P, 71V, 74P, 77I, 84V, 89V, 90M, 93L | 3 | 50 | >200 | 40 | >200 | 52 | 37 | 17 | 286 |
| 14311 | 4.8 | 136 | 7 | 3 | APV/r, ATV/r, LPV/r, FPV + LPV/r | 10F, 11I, 32I, 35A, 36I, 46I, 47V, 54M, 57K, 62V, 63P, 64V, 73T, 74A, 84V, 89V, 90M | 4 | 120 | >200 | 48 | >200 | 50 | 22 | 8 | 245 |
| 38129 | 4.5 | 22 | ≥4 | ≥3 | IDV, ATV/r, DRV/r | 10I, 11I, 12K, 13V, 20V, 32I, 33F/L, 35G, 36I, 37D/N, 46I, 47V, 54M, 57K, 58E, 63P, 64V, 71V/I, 73S, 84V/I, 89V, 90M | 3 | 97 | >200 | 55 | >200 | 80 | 26 | >200 | >200 |
VL, plasma HIV-1 RNA level (log copies/mL); CD4, CD4+ lymphocytes (cells/mm3); RC, replication capacity; ATV, atazanavir; DRV, darunavir; FPV, fosamprenavir; IDV, indinavir; LPV, lopinavir; NA, not available; NFV, nelfinavir; SQV, saquinavir; TPV, tipranavir.
The GenBank accession numbers for the direct PCR sequences are as follows: GQ211137 (1456), AY796708 (1459), pending (1556), GQ212652 (4736), AY797430 (6585), pending (7118), GQ213748 (7859), pending (14311), GQ213273 (38129).
a‘/r’ following the PI abbreviation indicates ritonavir co-administration for pharmacokinetic boosting; ‘+’ indicates the simultaneous use of two PIs.
bMutations in bold are major PI resistance mutations. Underlined mutations are non-polymorphic PI-selected mutations and the minimally polymorphic PI-selected mutations L10IV, V11I, L33F and A71VT.
cThe last eight columns indicate the fold decrease in susceptibility for each PI as determined by the PhenoSense assay. Those in bold are considered highly resistant according to the PhenoSense clinical cut-off. Each of the nine viruses displayed high-level ritonavir resistance (data not shown).