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. 2004 Aug;48(8):3122–3126. doi: 10.1128/AAC.48.8.3122-3126.2004

Distribution of Human Immunodeficiency Virus Type 1 Protease and Reverse Transcriptase Mutation Patterns in 4,183 Persons Undergoing Genotypic Resistance Testing

Soo-Yon Rhee 1, Tommy Liu 1, Jaideep Ravela 1, Matthew J Gonzales 1, Robert W Shafer 1,*
PMCID: PMC478552  PMID: 15273130

Abstract

In a sample of 6,156 sequences from 4,183 persons, the top 30 patterns of protease inhibitor, nucleoside reverse transcriptase (RT) inhibitor, and nonnucleoside RT inhibitor mutations accounted for 55, 46, and 66%, respectively, of sequences with drug resistance mutations. Characterization of the phenotypic and clinical significance of these common patterns may lead to improved treatment recommendations for a large proportion of patients for whom antiretroviral therapy is failing.


The optimal regimens for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection have become increasingly well defined (6). However, the management of persons who develop HIV-1 drug resistance or who are infected primarily with a drug-resistant virus remains a clinical challenge. Genotypic testing for HIV-1 drug resistance is useful for selecting antiretroviral drugs for patients developing treatment failure, but the optimal means for interpreting genotypic tests is not known because many HIV-1 protease and reverse transcriptase (RT) mutations contribute to drug resistance.

To identify common combinations of drug resistance mutations and to determine their contribution to the burden of HIV-1 drug resistance, we examined HIV-1 protease and RT sequences from a clinic-based population tested at Stanford University Hospital. Identifying common patterns of drug resistance mutations is important for determining which mutation patterns should be examined for their phenotypic and clinical significance.

Patients, sequences, mutations, and drug susceptibility data.

Between July 1997 and September 2003, 6,153 protease sequences and 6,156 RT sequences were determined for HIV-1 isolates from 4,183 persons in Northern California at the request of their physicians. Two thousand, nine hundred forty-seven persons had one sequence. Seven hundred ninety-eight persons had 2 sequences, 257 persons had 3 sequences, and 181 persons had 4 or more sequences. Forty-nine sequences from 32 persons belonged to a non-B subtype, including 27 subtype C sequences, 15 subtype A sequences, and 7 subtype D sequences.

Protease inhibitor (PI) resistance mutation patterns were defined by mutations at 14 nonpolymorphic protease positions associated with PI resistance: positions 24, 30, 32, 46, 47, 48, 50, 53, 54, 73, 82, 84, 88, and 90. Nucleoside RT inhibitor (NRTI) resistance mutation patterns were defined by mutations at 18 RT positions associated with NRTI resistance: positions 41, 44, 62, 65, 67, 69, 70, 74, 75, 77, 115, 116, 118, 151, 184, 210, 215, and 219. Nonnucleoside RT inhibitor (NNRTI) resistance mutation patterns were defined by mutations at 15 positions associated with NNRTI resistance: positions 98, 100, 101, 103, 106, 108, 179, 181, 188, 190, 225, 227, 230, 236, and 238.

Drug resistance mutations at polymorphic protease positions (positions10, 20, 33, 36, 63, 71, 77, and 93) were not used to define PI mutation patterns. Two common polymorphisms at NNRTI resistance positions, A98S and V179I (5), were not used to define NNRTI mutation patterns. Drug resistance mutations consisting of mixtures of wild-type and mutant variants were classified as mutant. Sequences with a mixture of more than one drug resistance mutation at the same position were excluded from analysis.

Drug susceptibility data obtained with the PhenoSense assay (ViroLogic, South San Francisco, Calif.) (4) on isolates matching specific mutation patterns were obtained from the Stanford HIV RT and Protease Sequence Database (5).

Summary of drug resistance mutations.

Of 6,153 isolates, 21.3% had no drug resistance mutations, 22.6% had mutations associated with resistance to one drug class (15.4% NRTI, 5.7% NNRTI, and 1.5% PI), 34.3% had mutations associated with resistance to two drug classes (20.8% NRTI and PI, 12.4% NRTI and NNRTI, and 1.1% NNRTI and PI), and 21.8% had mutations associated with resistance to three drug classes.

PI patterns.

Among the 6,153 protease sequences, 2,934 (47.7%) had a mutation at one or more of the 14 nonpolymorphic PI resistance positions. Of these sequences, 139 (4.7%) had a mixture of two mutations at the same position and were excluded from analysis. The top 30 PI patterns accounted for 54.5% of the 2,795 mutant sequences (Table 1), and 523 additional patterns accounted for the remaining 45.5% mutant sequences (Fig. 1). Of these additional 523 patterns, 204 (677 sequences) had one of the top 30 patterns plus one additional drug resistance mutation.

TABLE 1.

Top 30 HIV-1 PI resistance patterns in 2,795 sequences from 2,275 persons with PI resistance mutations, 1997 to 2003

Mutation pattern No. (%) of sequencesa No. of personsa Cumulative % Susceptibility to drug (foldn)b
NFV SQV IDV RTV APV LPV ATV
D30N, N88D 249 (8.9) 210 8.9 5218 2.017 1.718 1.418 0.915 0.95 3.610
L90M 245 (8.8) 206 17.7 3.29 1.410 1.310 2.610 1.26 0.33 3.02
D30N 130 (4.7) 117 22.3 1410 0.510 0.910 0.610 0.58 0.62 1.85
M46I, L90M 89 (3.2) 71 25.5 8.09 2.19 118 7.07 4.86 2.62 2.11
G73S, L90M 66 (2.4) 54 27.9 274 9.24 7.94 5.34 1.34 1.33 2.01
I54V, V82A, L90M 60 (2.1) 45 30.0 379 7.99 169 839 3.07 206 5.03
L24I, M46L, I54V, V82A 52 (1.9) 35 31.9 396 7.16 205 804 4.04 343 191
V82I 51 (1.8) 40 33.7 3.65 1.35 0.75 1.75 1.15 0.83 1.32
G73S, I84V, L90M 50 (1.8) 41 35.5 343 703 193 443 4.52 7.23 151
M46L, I54V, V82A, L90M 49 (1.8) 34 37.2 394 9.14 224 784 5.64 332
I84V, L90M 39 (1.4) 31 38.6 196 186 9.66 175 3.86 3.14 10.01
M46I, N88S 37 (1.3) 30 40.0 197 1.47 6.17 1.77 0.26 0.81
M46I, G73S, L90M 31 (1.1) 26 41.1 223 3.43 8.33 4.43 1.62 3.03
I54V, V82A 30 (1.1) 29 42.1 129 1.49 8.39 288 3.07 2.31 6.04
M46L 29 (1.0) 24 43.2 4.41 0.91 2.81 3.11 1.41 1.71
M46I, I84V, L90M 29 (1.0) 22 44.2 165 10.05 9.75 194 5.04 7.94
M46I 26 (0.9) 21 45.1 3.43 0.83 7.83 5.93 2.23 6.91
V82A 26 (0.9) 20 46.1 3.41 0.91 2.71 4.01 1.71 4.71 1.91
M46I, I54V, V82A, L90M 26 (0.9) 18 47.0 752 232 372 1482 112 641
M46I, G73S, I84V, L90M 24 (0.9) 19 47.9 623 883 533 433 113 213 242
D30N, N88D, L90M 21 (0.8) 20 48.6 7410 5.410 3.010 3.510 1.310 4.01
N88S 21 (0.8) 19 49.4 8.913 1.213 2.513 0.813 0.113 0.51 10.02
G48V, I54V, V82A 21 (0.8) 15 50.1 283 1473 253 413 3.03 323 293
V32I, M46I, V82A, L90M 20 (0.7) 14 50.8 252 4.52 272 452 142 122 202
L24I, M46I, I54V, V82A 18 (0.6) 15 51.5 146 1.46 195 503 2.13 171
F53L, I54V, V82A, L90M 18 (0.6) 13 52.1 352 242 142 1072 3.12 302
L24I, M46L, V82A 18 (0.6) 12 52.8 6.11 1.31 7.41 451 5.81 7.01
M46L, V82A 17 (0.6) 12 53.4 5.52 1.12 6.32 132 4.52 6.62 2.52
M46L, L90M 17 (0.6) 11 54.0 122 3.32 8.82 7.12 4.12 4.01
D30N, M46I, N88D 15 (0.5) 15 54.5 251 0.91 1.21 1.01 0.81
a

Of 4,183 persons, 2,275 had 2,795 mutant sequences with 553 different PI mutation patterns. The top 30 patterns accounted for 54.5% of 2,795 mutant sequences.

b

Median susceptibility results (n-fold) for isolates with matching patterns of mutations. The subscript is the number of samples for which susceptibility results are available. Results that are ≥2.5-fold the susceptibility of the wild-type control are shown in bold. Abbreviations: NFV, nelfinavir; SQV, saquinavir; IDV, indinavir; RTV, ritonavir; APV, amprenavir; LPV, lopinavir; ATV, atazanavir.

FIG. 1.

FIG. 1.

Percentage of mutant sequences explained by the 553 different PI resistance mutation patterns (dashed line), 1,120 NRTI resistance mutation patterns (solid line), and 411 NNRTI resistance mutation patterns (dotted line). The top 30 PI, NRTI, and NNRTI resistance mutation patterns accounted for 55, 46, and 66%, respectively, of all sequences with drug resistance mutations.

The top 30 PI patterns were associated with decreased susceptibility (>2.5-fold increase in the 50% inhibitory concentration [IC50] of drug) to a median of five PIs (Table 1). These patterns included mutations at 12 of 14 nonpolymorphic PI resistance positions and had a median of 2.5 PI resistance mutations: 7 patterns with 1 mutation, 8 patterns with 2 mutations, 8 patterns with 3 mutations, and 7 patterns with 4 mutations. The remaining 523 patterns had a median of 4 nonpolymorphic PI resistance mutations (data not shown).

L90M was the most common mutation, occurring in 15 patterns and 28.1% of viruses. Each of the top 30 patterns was common in the first and second halves of the study (data not shown), except for G48V/I54V/V82A, which decreased from 18 sequences between 1997 and 2000 to 3 sequences between 2001 and 2003 (P < 0.001).

NRTI patterns.

Among the 6,156 RT sequences, 4,517 (73.4%) had a mutation at 1 or more of the 18 NRTI resistance positions. Of these sequences, 428 (9.5%) had a mixture of two mutations at the same position and were excluded from analysis. The top 30 NRTI patterns accounted for 46.0% of the 4,089 mutant sequences (Table 2), and 1,090 additional patterns accounted for the remaining 54.0% of mutant sequences (Fig. 1). Of these additional 1,090 patterns, 250 (784 sequences) had 1 of the top 30 patterns plus 1 additional drug resistance mutation.

TABLE 2.

Top 30 HIV-1 NRTI resistance patterns in 4,089 sequences from 3,550 persons with NRTI resistance, 1997 to 2003

Mutation pattern No. (%) of sequencesa No. of personsa Cumulative % Susceptibility to drug (foldn)b
ZDV D4T TDF ABC DDI 3TC
M184V 710 (17.4) 609 17.4 0.530 0.832 0.64 3.132 1.530 >20031
M41L, M184V, T215Y 156 (3.8) 125 21.2 5.513 1.513 1.03 5.115 1.513 >20013
M41L, M184V, L210W, T215Y 100 (2.4) 88 23.7 159 1.89 1.24 6.110 1.79 >2009
M41L, T215Y 82 (2.0) 71 25.7 123 1.83 2.63 1.23 2.03
D67N, K70R, M184V, K219Q 79 (1.9) 61 27.6 7.52 1.42 1.61 5.22 1.62 >2002
K70R, M184V 65 (1.6) 55 29.2 1.11 0.71 2.21 1.51 >2002
M41L, L210W, T215Y 56 (1.4) 48 30.6 2632 2.12 3.42 3.02 1.22 1.82
M184V, T215Y 50 (1.2) 42 31.8 1.14 1.24 0.52 5.24 1.94 >2004
V118I 48 (1.2) 44 33.0 1.01 0.91 1.01 1.11 1.01
T215Y 38 (0.9) 31 33.9 117 1.57 1.46 1.37 1.17 1.77
M41L, V118I, M184V, L210W, T215Y 37 (0.9) 31 34.8 5.53 2.33 1.82 5.53 1.73 >2003
M41L, D67N, V118I, L210W, T215Y 35 (0.9) 30 35.6 2,4001 6.91 5.61 6.61 2.31 7.81
L74V, M184V 33 (0.8) 31 36.5 0.31 1.01 5.32 2.61 >2001
D67N, K70R, M184V 32 (0.8) 27 37.2 1.12 1.02 0.71 3.02 1.32 >2002
D67N, T69N, K70R, M184V, K219Q 28 (0.7) 22 37.9 7.91 2.31 7.71 1.81 >2001
M41L, D67N, M184V, L210W, T215Y 27 (0.7) 24 38.6 306 2.66 2.12 6.45 1.96 >2006
M41L, M184V 27 (0.7) 19 39.2 0.51 0.61 0.41 1.61 1.41 >2001
A62V, M184V 26 (0.6) 22 39.9 0.31 0.71 0.41 3.81 1.91 >2001
M41L, E44D, D67N, V118I, M184V, L210W, T215Y 25 (0.6) 20 40.5 541 3.21 2.01 6.61 2.01 >2001
D67N, K70R, M184V, T215F, K219Q 25 (0.6) 19 41.1 7.71 1.51 1.11 6.51 1.71 >2001
D67N, K70R, K219Q 24 (0.6) 24 41.7 262 1.82 1.82 0.92 1.43
D67N, K70R 24 (0.6) 20 42.3 172 0.92 1.52 1.02 0.82 1.42
L74V 21 (0.5) 19 42.8 1.11 0.91 1.81 2.61
M41L, M184V, T215F 21 (0.5) 17 43.3 4.63 1.63 5.83 2.03 >2003
M41L, V118I, L210W, T215Y 21 (0.5) 16 43.8 131 1.91 2.01 1.11 1.42
M41L, D67N, L210W, T215Y 18 (0.4) 18 44.3 1,0003 2.43 5.03 4.53 1.63 4.03
T69N, K70R 18 (0.4) 17 44.7 7.02 0.82 1.32 0.82 0.82 0.82
M41L, E44D, D67N, V118I, L210W, T215Y 18 (0.4) 17 45.1 1191 3.61 2.31 1.61 4.41
M41L, L74V, M184V, T215Y 18 (0.4) 17 45.6 0.71 1.22 6.31 1.82 >2002
T69N 18 (0.4) 16 46.0 0.52 0.92 0.82 1.12 1.12 2.32
a

Of 4,183 persons, 3,550 had 4,089 mutant sequences with 1,120 different NRTI mutation patterns. The top 30 patterns accounted for 46.0% of the mutant sequences.

b

Median susceptibility results (n-fold) for isolates with matching patterns of mutations. The subscript is the number of samples with available susceptibility results. Results above the PhenoSense reduced susceptibility cutoff (≥1.9 for ZDV, ≥1.7 for D4T, ≥1.4 for TDF, ≥4.5 for ABC, ≥1.7 for DDI, and ≥3.5 for 3TC [fold]) are shown in bold. Abbreviations: ZDV, zidovudine; D4T, stavudine; TDF, tenofovir; ABC, abacavir; DDI, didanosine; 3TC, lamivudine.

The top 30 NRTI patterns were associated with decreased susceptibility (>1.4-fold to >4.5-fold increase in IC50 depending on the drug) to a median of three of six NRTIs (Table 2). These patterns had a median of three NRTI resistance mutations: five with one mutation, eight with two mutations, five with three mutations, five with four mutations, five with five mutations, and one each with six and seven mutations. The remaining 1,090 patterns had a median of 5 NRTI-resistance mutations (data not shown).

M184V was the most common NRTI resistance mutation, occurring alone in 17.4% of mutant sequences and in 16 patterns. T215Y occurred with the next-highest frequency and was in 14 patterns. Mutations at positions 65, 75, 77, 115, 116, and 151 did not occur among the top 30 patterns. Each of the top 30 patterns was common in the first and second halves of the study (data not shown), although significant increases were observed in the patterns A62V/M184V (P < 0.001) and T69N (P = 0.001). K65R was in 1.6% of mutant sequences, occurring alone in 10 sequences and in combination with M184V in 18 sequences, in combination with Q151 M in 15 sequences, and in combination with M184V and Q151 M in 8 sequences. The frequency of K65R increased from 1.2 to 1.9% between the first and second halves of the study (P value not significant).

NNRTI patterns.

Among the 6,156 RT sequences, 2,658 (43.2%) had a mutation at one or more of the 15 NNRTI resistance positions. Of these sequences, 132 (5.0%) had a mixture of two mutations at the same position and were excluded from analysis. The top 30 NNRTI mutation patterns accounted for 66.2% of mutant sequences (Table 3), and 381 additional patterns accounted for the remaining 33.8% of mutant sequences (Fig. 1). Of these additional 381 patterns, 210 (503 sequences) had 1 of the top 30 patterns plus 1 additional drug resistance mutation.

TABLE 3.

Top 30 HIV-1 NNRTI resistance patterns in 2,526 sequences from 2,168 persons with NNRTI resistance, 1997 to 2003

Mutation pattern No. (%) of sequencesa No. of personsa Cumulative % Susceptibility to drug (foldn)b
NVP DLV EFV
K103N 459 (18.2) 379 18.2 4621 3421 1920
K103N, Y181C 149 (5.9) 126 24.1 4007 2507 468
Y181C 116 (4.6) 100 28.7 1046 306 1.06
L100I, K103N 116 (4.6) 99 33.3 789 1039 2749
K103R 93 (3.7) 74 36.9 0.52 0.92 0.52
Y188L 51 (2.0) 32 39.0 5005 9.05 1095
V106I 50 (2.0) 46 40.9 0.33 0.13 0.23
A98G 46 (1.8) 44 42.8 3.66 0.76 0.85
K103N, V108I 44 (1.7) 41 44.5 2182 652 792
K101E, G190A 44 (1.7) 33 46.2 5001 2.01 1231
K101Q 38 (1.5) 35 47.7 2.21 1.41 2.11
K101R 34 (1.3) 31 49.1 0.32 0.32 0.32
K103N, P225H 34 (1.3) 28 50.4 954 104 1044
K103N, Y181C, G190A 33 (1.3) 29 51.7 2401 1901 2401
K103N, G190A 31 (1.2) 29 53.0 5001 371 2131
V108I 30 (1.2) 25 54.2 3.01 1.31 1.71
Y181C, G190A 29 (1.1) 25 55.3 4903 7.23 113
K101E 29 (1.1) 20 56.5 121 4.91 5.01
V179D 27 (1.1) 22 57.5 0.71 2.91 1.41
K103N, K238T 26 (1.0) 24 58.6 1522 252 472
K238R 23 (0.9) 21 59.5 0.51 0.21 0.21
G190A 22 (0.9) 21 60.3 755 0.45 7.05
K101P, K103N 22 (0.9) 16 61.2 4001 2501 7001
V108I, Y181C 20 (0.8) 18 62.0 4002 402 4.92
K101E, Y181C, G190A 20 (0.8) 15 62.8 5472 212 1032
A98G, K103N 19 (0.8) 16 63.5 1214 254 324
G190S 18 (0.7) 16 64.3 2063 0.43 473
K103N, V108I, Y181C 17 (0.7) 15 64.9 4001 2501 7001
K103N, Y188L 17 (0.7) 12 65.6 6801 1901 2701
K103N, M230L 16 (0.6) 16 66.2 6902 2502 3602
a

Of the 4,183 persons in this study, 2,168 had 2,526 mutant sequences with 411 different NNRTI mutation patterns. The top 30 patterns accounted for 66.2% of the 2,526 mutant sequences.

b

Median susceptibility results (n-fold) for isolates with matching patterns of drug resistance mutations. The subscript is the number of samples for which susceptibility results are available. Results that are ≥2.5-fold the wild-type control result are shown in bold. Abbreviations: NVP, nevirapine; DLV, delavirdine; EFV, efavirenz.

The top 30 NNRTI patterns were associated with decreased susceptibility (>2.5-fold increase in IC50 of drug) to a median of three NNRTIs (Table 3). These patterns had a median of 2 NNRTI resistance mutations: 14 with 1 mutation, 13 with 2 mutations, and 3 with 3 mutations. The remaining 381 patterns had a median of 3 NNRTI resistance mutations (data not shown).

K103N was the most common NNRTI resistance mutation, occurring alone in 18.2% of sequences and in 12 of the remaining patterns. The top 30 patterns included mutations at 13 of the 15 NNRTI resistance positions. Mutations at positions 227 and 236 were uncommon, occurring in 62 and 4 sequences, respectively. Four of the patterns—K103R, V106I, K101R, and K238R—are polymorphisms that do not occur with increased frequency in persons receiving NNRTIs and do not confer phenotypic resistance (Table 3). Three of the top 30 patterns included mutations (K101P, M230L, and K238T) that have only recently been recognized as causing NNRTI resistance (W. Huang, N. T. Parkin, Y. S. Lie, T. Wrin, R. Haubrich, S. Deeks, N. Hellmann, C. J. Petropoulos, and J. M. Whitcomb, abstract from the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy 2000, Antivir. Ther. 5(Suppl. 3):24-25, 2000; C. J. Petropoulos, C. Chappey, and N. T. Parkin, Abstr. 43rd Intersci. Conf. Antimicrob. Agents Chemother., abstr. H-451, 2003). There was no significant change in the NNRTI resistance patterns between the first and second halves of the study (data not shown).

Consistency of drug susceptibility results within each pattern.

With the exception of atazanavir and tenofovir, multiple drug susceptibility results were available for most patterns of drug resistance mutations (Table 4). The mean absolute deviation in resistance (n-fold) from the median susceptibility for each pattern ranged from 0.05 log10 (1.1-fold) for stavudine and didanosine to 0.32 log10 for delavirdine (2.1-fold), suggesting that results were consistent within most patterns of drug-resistance mutations.

TABLE 4.

Consistency of drug susceptibility results within the top 30 patterns of drug resistance mutations for each drug class

Drug class Drug Isolates with patterns for which more than one susceptibility result is available
Mean absolute deviation in fold resistance from the median value of each pattern (log scale)a
No. of patterns No. of isolates
NRTI ZDV 17 95 0.21
D4T 18 99 0.05
TDF 12 34 0.10
ABC 18 101 0.09
DDI 18 97 0.05
3TC 20 103 ND
NNRTI NVP 19 90 0.23
DLV 19 90 0.32
EFV 19 89 0.24
PI NFV 26 155 0.22
SQV 26 155 0.19
IDV 26 153 0.18
RTV 26 146 0.16
APV 26 131 0.15
LPV 18 55 0.12
ATV 11 37 0.17
a

For 67% of mutant isolates, the 3TC IC50 was above the limit of detection of the assay and was censored at 200-fold, making it impossible to examine the consistency of results for most patterns. Abbreviations: ZDV, zidovudine; D4T, stavudine; TDF, tenofovir; ABC, abacavir; DDI, didanosine; 3TC, lamivudine; NVP, nevirapine; DLV, delavirdine; EFV, efavirenz; NFV, nelfinavir; SQV, saquinavir; IDV, indinavir; RTV, ritonavir; APV, amprenavir; LPV, lopinavir; ATV, atazanavir.

Conclusions.

In this sample of >6,000 sequences from nearly 4,200 persons, the top 30 PI, NRTI, and NNRTI mutation patterns accounted for 55, 46, and 66%, respectively, of all sequences with drug resistance mutations. A much larger number of mutation patterns, however, were required to account for the remaining mutant sequences. Studies that examine the clinical significance of drug resistance mutations should focus on the commonly occurring patterns of mutations that we identified in this analysis, because they affect the largest numbers of patients and form the foundation for many of the more complex patterns.

Although about one-third of patients had more than one sequence, clustering of patterns within patients did not explain the observed patterns, because nearly identical patterns were observed in analyses that considered only one sequence per patient (Tables 1 to 3, footnotes). All the HIV-1 isolates in this study were from northern California; however, we have previously shown with heavily treated persons that the patterns of drug resistance mutations in northern California are similar to those in subtype B sequences from other parts of the world (3). Although each of the known protease and RT drug resistance mutations occurs in non-B-subtype isolates (R. Kantor, D. Katzenstein, R. Camacho, P. R. Harrigan, A. Tanuri, D. Pillay, A.-M. Vandamme, P. Phanuphak, W. Sugiura, V. Soriano, L. Morris, Z. Grossman, L. F. Brigido, J. Schapiro, and R. W. Shafer, Abstr. 10th Conf. Retrovir. Opportun. Infect., abstr. 623, 2003), preliminary data suggest that the patterns of these mutations may be different in other subtypes (1, 2; Z. Grossman, E. Paxinos, D. Auerbuch, S. Maayan, N. Parkin, D. Engelhard, M. Lorber, E. Kedem, F. Mileguir, N. Vardinon, Z. Bentwich, C. Petropoulos, and J. M. Schapiro, abstract from the 11th International HIV Drug Resistance Workshop 2002, Antivir. Ther. 7:S39, 2002).

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