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. 2012 Jan 11;205(4):557–567. doi: 10.1093/infdis/jir821

Table 3.

Dynamics of Raltegravir Resistance Mutations Detected by Ultra-Deep-454 Pyrosequencing (UDPS)

A: Patient Who Developed Primary Resistance Y143R Mutation
Mutationsa
 Linked Mutations
Patient and Time, mo HIV RNA, log10 copies/mL L74M E92Q T97A T112Ab Y143R E157Q Reads Analyzed, Mean ± SD Mutationsc Haplotypes, % Haplotypes, No.
12 0 4.9 0 0 99.0 0 0 0 5266 ± 991 97A 99.6 2746
1 5.0 0 1.9 99.8 0 95.0 0 9591 ± 3496 97A, 143R 97.9 2986
92Q, 97A 1.8
3 5.2 0 0 99.6 0 99.8 0 10 809 ± 3912 97A, 143R 100.0 3368
7 5.1 1.7 0 99.4 31.0 99.7 0 12 805 ± 3083 97A, 143R 100.0 427
9 4.8 3.3 0 99.4 40.1 99.7 1.1 11 963 ± 3059 97A, 143R 97.8 808
97A, 112A, 143R 2.2
12 4.8 9.0 0 99.7 66.9 99.6 6.9 12 154 ± 3199 97A, 143R 65.7 487
97A, 112A, 143R 33.6
B: Patients Who Developed Primary Resistance Q148H/R Mutations
Mutationsa
 Linked Mutations
Patient and Time, mo HIV RNA, log10 copies/mL G140A G140S Q148H Q148R Q140K V151I Reads Analyzed, Mean ± SD Mutationsc % Haplotypes, No.
27 0 3.5 0 0 11 286 ± 2893 Wild type 100.0 4522
10 3.6 99.4 99.4 10 604 ± 2618 140S, 148H 100.0 5241
84 0 5.7 0 0 0 0 6312 ± 2047 Wild type 100.0 1771
1 3.2 0 0 1.5 0 11 012 ± 2973 Wild type 100.0 5678
2 2.7 0 0 15.8 1.6 13 480 ± 3494 148R 15.7 7488
3 4.7 4.3 34.0 63.3 0 6870 ± 2603 148R 69.8 1443
140S, 148R 12.0
4 5.4 1.0 66.7 70.7 0 7116 ± 2363 140S, 148R 76.1 2362
5 5.1 3.7 68.1 76.3 0 5647 ± 2275 140S, 148R 84.3 1198
3d 5.5 0 1.6 1.8 0 6089 ± 1595 140S, 148R 1.3 1810
9d 5.8 0 0 1.2 0 10 909 ± 2952 Wild type 100.0 2908
C: Patients Who Developed Primary Resistance N155H Mutation
Mutationsa
 Linked Mutations
Patient and Time, mo HIV RNA, log10 copies/mL L74M E92Ab E92Q T97A Y143C V151I N155H E157Q G163R Reads Analyzed, Mean ± SD Mutationsc % Haplotypes, No.
69 0 4.4 0 0 0 0 0 5014 ± 2215 Wild type 100.0 28
155H 51.3
5 3.8 30.6 4.1 6.5 98.1 2.2 4501 ± 768 92A, 155H 38.6 2767
151I, 155H 6.4
92Q, 155H 4.3
151I, 155H 41.8
92Q, 155H 22.1
7 3.6 8.7 21.2 41.6 97.4 4.3 5704 ± 1443 155H 21.0 1766
92A, 155H 11.6
155H, 163R 2.4
81 0 5.3 0 1190 ± 430 Wild type 100.0 856
3 5.1 65.3 9861 ± 4011 155H 64.5 2767
141 0 4.9 98.3 0 0 0 9261 ± 2439 151I 100 5832
151I, 155H 62.5
6 4.3 99.8 98.7 2.0 37.2 10 088 ± 2542 151I, 155H, 163R 35.6 6433
151I, 155H, 157Q, 163R 1.8
145 0e 5.0 0 0 0 11 820 ± 3254 Wild type 100.0 6514
155H 85.0
10e 3.2 96.5 14.9 99.6 9195 ± 2522 151I, 155H 15.0 5580
229 0e 4.7 0 0 0 0 0 9300 ± 2361 Wild type 100 5164
143C, 155H 89.2
7e 5.7 15.0 88.9 10.2 98.0 0 12 615 ± 3555 151I, 155H 8.7 8922
143C, 151I, 155H 1.1
143C, 155H 89.9
9e 5.7 15.1 88.3 10.6 98.3 0 11 999 ± 3271 151I, 155H 8.9 8201
143C, 151I, 155H 1.2
143C, 155H 90.6
11e 4.1 0 99.2 10.3 99.4 10.0 12 231 ± 3263 143C, 151I, 155H, 157Q 9.4 8790

Data include percentage of reads of raltegravir resistance mutations (as percentage ratio of number of reads mutated /total number of reads detected at each specific position) from integrase positions 66–163 (http://hivdb.stanford.edu/cgi-bin/INIResiNote.cgi [16]; Johnson et al, 2010 [14]) over time, relative mean ± standard deviation of reads detected at each specific position and HIV RNA level for patients with raltegravir failure. Linkage of resistance mutations is given as prevalence in unique overlapping sequences obtained with UDPS (haplotypes spanning amino acids 90–163) with the number of haplotypes reconstructed for each time point/patient.

a

Only raltegravir resistance mutations found in each patient are reported. Mutations F121Y-E138A/K-Y143H-S147G-Q148K were never detected. The first letter represents the wild type aminoacid (according to consensus B), followed by the integrase position and finally the mutated aminoacid.

b

Novel mutations.

c

Raltegravir-resistance and novel mutations found in haplotypes; “wild type” indicates haplotype without mutations.

d

Samples obtained after raltegravir interruption.

e

For these patients, only haplotypes spanning amino acid 130–163 integrase positions were available.