Table 2.
Accumulated resistance to trial end
| NNRTI and PI Resistance
| ||||||||
|---|---|---|---|---|---|---|---|---|
| Total (n=263) | PI (n=131) | NNRTI (n=132) | rate-ratio [95%CI]; p | 1000 (n=134) | 30000 (n=129) | rate-ratio [95%CI]; p | ||
| Children expected to have tests | [number of tests] | 108 [165] | 56 [90] | 52 [75] | 60 [89] | 48 [76] | ||
| Children with tests | [number of tests] | 91 [128a] | 46 [69] | 45 [59] | 51 [67] | 40 [61] | ||
|
| ||||||||
| (n=246) | (n=121) | (n=125) | (n=125) | (n=121) | ||||
|
| ||||||||
| Number of major NNRTI mutations | none | 204 (83%) | 112 (93%) | 92 (74%) | 3.12 [1.84,5.29]; <0.001 | 104 (83%) | 100 (83%) | 1.15 [0.73,1.80]; 0.50 |
| 1–2 | 34 (14%) | 7 (6%) | 27 (22%) | 18 (14%) | 16 (13%) | |||
| 3 or more | 8 (3%) | 2 (2%) | 6 (5%) | 3 (2%) | 5 (4%) | |||
|
| ||||||||
| High-level NNRTI resistance (% of all children) | neviparine | 42 (17%) | 9 (7%) | 33 (26%) | 21 (17%) | 21 (17%) | ||
| efavirenz | 38 (15%) | 9 (7%) | 29 (23%) | 20 (16%) | 18 (15%) | |||
| etravirine | 3 (1%) | 3 (2%) | 1 (1%) | 2 (2%) | ||||
|
| ||||||||
| Number of major PI mutations | none | 230 (93%) | 108 (89%) | 122 (98%) | 0.25 [0.10,0.68]; 0.01 | 114 (91%) | 116 (96%) | 0.62 [0.27,1.42]; 0.27 |
| 1–2 | 16 (7%) | 13 (11%) | 3 (2%) | 11 (9%) | 5 (4%) | |||
|
| ||||||||
| High-level PI resistanceb (% of all children) | nelfinavir | 11 (4%) | 9 (7%) | 2 (2%) | 6 (5%) | 5 (4%) | ||
| atazanavir | 3 (1%) | 2 (2%) | 1 (1%) | 1 (1%) | 2 (2%) | |||
| saquinavir | 1 (<1%) | 1 (1%) | 1 (1%) | |||||
|
| ||||||||
| NRTI Resistance (test for interaction, p=0.003)
| ||||||||
| Total (n=263) | PI-1000 (n=66) | PI-30000 (n=65) | rate-ratio [95%CI]; p | NNRTI-1000 (n=68) | NNRTI-30000 (n=64) | rate-ratio [95%CI]; p | ||
|
| ||||||||
| Children expected to have tests | [number of tests] | 108 [165] | 33 [48] | 23 [42] | 27 [41] | 25 [34] | ||
| Children with tests | [number of tests] | 91 [128a] | 28 [38] | 18 [31] | 23 [29] | 22 [30] | ||
|
| ||||||||
| (n=246) | (n=61) | (n=60) | (n=64) | (n=61) | ||||
|
| ||||||||
| Number of major NRTI mutations | none | 192 (78%) | 49 (80%) | 51 (85%) | 0.71 [0.37,1.34]; 0.31 | 50 (78%) | 42 (69%) | 2.53 [1.44,4.45]; 0.001 |
| 1–2 | 41 (17%) | 9 (15%) | 6 (10%) | 14 (22%) | 12 (20%) | |||
| 3 or more | 13 (5%) | 3 (5%) | 3 (5%) | 7 (11%) | ||||
|
| ||||||||
| Number of TAMs | none | 227 (92%) | 58 (95%) | 56 (93%) | 61 (95%) | 52 (85%) | ||
| 1–2 | 15 (6%) | 3 (5%) | 4 (7%) | 3 (5%) | 5 (8%) | |||
| 3 or more | 4 (2%) | 4 (7%) | ||||||
|
| ||||||||
| High-level NRTI resistance (% of all children) | zidovudine | 2 (1%) | 2 (3%) | |||||
| didanosine | 7 (3%) | 3 (5%) | 1 (2%) | 3 (5%) | ||||
| lamivudine / emtricitabinec | 49 (20%) | 12 (20%) | 8 (13%) | 12 (19%) | 17 (28%) | |||
| stavudine | 3 (1%) | 3 (5%) | ||||||
| abacavir | 8 (3%) | 3 (5%) | 1 (2%) | 1 (2%) | 3 (5%) | |||
| tenofovir | 1 (<1%) | 1 (2%) | ||||||
PI = protease inhibitor, NNRTI = non-nucleoside reverse transcriptase inhibitor, NRTI = nucleoside reverse transcriptase inhibitor, TAMs = thymidine-analogue mutations
9 samples could not be amplified, 28 no stored sample available
No children developed high-level resistance to lopinavir, tipranavir, fosamprenavir or darunavir.
Since M184V/I mutation alone confers high-level resistance to lamivudine and emtricabine, this can be interpreted as the number of children acquiring M184V/I.
Note: 6 children developed the L74V mutation (3 PI-1000, 1 PI-30000, 2 NNRTI-30000) and 2 children developed the K65R mutation (1 PI-1000, 1 NNRTI-1000).
Note: Analysis assumed children not expected to have tests did not develop mutations and excluded children with missing tests.
Pair-wise comparisons between PI-1000 and NNRTI-1000: rate-ratio=0.70, 95%CI[0.38,1.32]; p=0.27; PI-30000 and NNRTI-30000: rate-ratio=2.52, 95%CI[1.41,4.49]; p=0.002