Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria

J Acquir Immune Defic Syndr. 2009 Oct 1;52(2):228-34. doi: 10.1097/QAI.0b013e3181b06125.

Abstract

Introduction: The HIV-1 epidemic in African countries is largely due to non-B HIV-1 subtypes. Patterns and frequency of antiretroviral drug resistance mutations observed in these countries may differ from those in the developed world, where HIV-1 subtype B predominates.

Methods: HIV-1 subtype and drug resistance mutations were assayed among Nigerian patients with treatment failure on first-line therapy (plasma HIV RNA >1000 copies/mL). Sequence analysis of the reverse transcriptase and protease gene revealed drug resistance mutations and HIV-1 viral subtype. Specific patterns of mutations and clinical characteristics are described in patients with the K65R mutation.

Results: Since 2005, 338 patients were evaluated. The most prevalent subtypes were CRF02_AG [152 of 338 (44.9%)] and G [128 of 338 (37.9%)]. Three hundred seven of 338 (90.8%) patients had previously received stavudine and/or zidovudine + lamivudine + efavirenz or nevirapine; 41 of 338 (12.1%) had received tenofovir (TDF). The most common nucleoside reverse transcriptase inhibitor mutations observed were M184V (301, 89.1%) and K70R (91, 26.9%). The K65R mutation was present in 37 of 338 patients (10.9%). The Q151M (P < 0.05), K219R, and T69del (P < 0.01) mutations were more common in patients with K65R who had not received TDF.

Conclusions: The K65R mutation is increasingly recognized and is a challenging finding among patients with non-B HIV subtypes, whether or not they have been exposed to TDF.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Substitution / genetics
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active*
  • Drug Resistance, Viral*
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV Protease
  • HIV Reverse Transcriptase / genetics
  • HIV-1 / classification
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification
  • Humans
  • Molecular Sequence Data
  • Mutation, Missense*
  • Nigeria
  • Sequence Analysis, DNA
  • Treatment Failure
  • Young Adult

Substances

  • Anti-HIV Agents
  • HIV Reverse Transcriptase
  • HIV Protease
  • p16 protease, Human immunodeficiency virus 1

Associated data

  • GENBANK/FJ931123
  • GENBANK/FJ931124
  • GENBANK/FJ931125
  • GENBANK/FJ931126
  • GENBANK/FJ931127
  • GENBANK/FJ931128
  • GENBANK/FJ931129
  • GENBANK/FJ931130
  • GENBANK/FJ931131
  • GENBANK/FJ931132
  • GENBANK/FJ931133
  • GENBANK/FJ931134
  • GENBANK/FJ931135
  • GENBANK/FJ931136
  • GENBANK/FJ931137
  • GENBANK/FJ931138
  • GENBANK/FJ931139
  • GENBANK/FJ931140
  • GENBANK/FJ931141
  • GENBANK/FJ931142
  • GENBANK/FJ931143
  • GENBANK/FJ931144
  • GENBANK/FJ931145
  • GENBANK/FJ931146
  • GENBANK/FJ931147
  • GENBANK/FJ931148
  • GENBANK/FJ931149
  • GENBANK/FJ931150
  • GENBANK/FJ931151
  • GENBANK/FJ931152
  • GENBANK/FJ931153
  • GENBANK/FJ931154
  • GENBANK/FJ931155
  • GENBANK/FJ931156
  • GENBANK/FJ931157
  • GENBANK/FJ931158
  • GENBANK/FJ931159
  • GENBANK/FJ931160
  • GENBANK/FJ931161
  • GENBANK/FJ931162
  • GENBANK/FJ931163
  • GENBANK/FJ931164
  • GENBANK/FJ931165
  • GENBANK/FJ931166
  • GENBANK/FJ931167
  • GENBANK/FJ931168
  • GENBANK/FJ931169
  • GENBANK/FJ931170
  • GENBANK/FJ931171
  • GENBANK/FJ931172
  • GENBANK/FJ931173
  • GENBANK/FJ931174
  • GENBANK/FJ931175
  • GENBANK/FJ931176
  • GENBANK/FJ931177
  • GENBANK/FJ931178
  • GENBANK/FJ931179
  • GENBANK/FJ931180
  • GENBANK/FJ931181
  • GENBANK/FJ931182
  • GENBANK/FJ931183
  • GENBANK/FJ931184
  • GENBANK/FJ931185
  • GENBANK/FJ931186
  • GENBANK/FJ931187
  • GENBANK/FJ931188
  • GENBANK/FJ931189
  • GENBANK/FJ931190
  • GENBANK/FJ931191
  • GENBANK/FJ931192
  • GENBANK/FJ931193
  • GENBANK/FJ931194
  • GENBANK/FJ931195
  • GENBANK/FJ931196
  • GENBANK/FJ931197
  • GENBANK/FJ931198
  • GENBANK/FJ931199
  • GENBANK/FJ931200
  • GENBANK/FJ931201
  • GENBANK/FJ931202
  • GENBANK/FJ931203
  • GENBANK/FJ931204
  • GENBANK/FJ931205
  • GENBANK/FJ931206
  • GENBANK/FJ931207
  • GENBANK/FJ931208
  • GENBANK/FJ931209
  • GENBANK/FJ931210
  • GENBANK/FJ931211
  • GENBANK/FJ931212
  • GENBANK/FJ931213
  • GENBANK/FJ931214
  • GENBANK/FJ931215
  • GENBANK/FJ931216
  • GENBANK/FJ931217
  • GENBANK/FJ931218
  • GENBANK/FJ931219
  • GENBANK/FJ931220
  • GENBANK/FJ931221
  • GENBANK/FJ931222
  • GENBANK/FJ931223
  • GENBANK/FJ931224
  • GENBANK/FJ931225
  • GENBANK/FJ931226
  • GENBANK/FJ931227
  • GENBANK/FJ931228
  • GENBANK/FJ931229
  • GENBANK/FJ931230
  • GENBANK/FJ931231
  • GENBANK/FJ931232
  • GENBANK/FJ931233
  • GENBANK/FJ931234
  • GENBANK/FJ931235
  • GENBANK/FJ931236
  • GENBANK/FJ931237
  • GENBANK/FJ931238
  • GENBANK/FJ931239
  • GENBANK/FJ931240
  • GENBANK/FJ931241
  • GENBANK/FJ931242
  • GENBANK/FJ931243
  • GENBANK/FJ931244
  • GENBANK/FJ931245
  • GENBANK/FJ931246
  • GENBANK/FJ931247
  • GENBANK/FJ931248
  • GENBANK/FJ931249
  • GENBANK/FJ931250
  • GENBANK/FJ931251
  • GENBANK/FJ931252
  • GENBANK/FJ931253
  • GENBANK/FJ931254
  • GENBANK/FJ931255
  • GENBANK/FJ931256
  • GENBANK/FJ931257
  • GENBANK/FJ931258
  • GENBANK/FJ931259
  • GENBANK/FJ931260
  • GENBANK/FJ931261
  • GENBANK/FJ931262
  • GENBANK/FJ931263
  • GENBANK/FJ931264
  • GENBANK/FJ931265
  • GENBANK/FJ931266
  • GENBANK/FJ931267
  • GENBANK/FJ931268
  • GENBANK/FJ931269
  • GENBANK/FJ931270
  • GENBANK/FJ931271
  • GENBANK/FJ931272
  • GENBANK/FJ931273
  • GENBANK/FJ931274
  • GENBANK/FJ931275
  • GENBANK/FJ931276
  • GENBANK/FJ931277
  • GENBANK/FJ931278
  • GENBANK/FJ931279
  • GENBANK/FJ931280
  • GENBANK/FJ931281
  • GENBANK/FJ931282
  • GENBANK/FJ931283
  • GENBANK/FJ931284
  • GENBANK/FJ931285
  • GENBANK/FJ931286
  • GENBANK/FJ931287
  • GENBANK/FJ931288
  • GENBANK/FJ931289
  • GENBANK/FJ931290
  • GENBANK/FJ931291
  • GENBANK/FJ931292
  • GENBANK/FJ931293
  • GENBANK/FJ931294
  • GENBANK/FJ931295
  • GENBANK/FJ931296
  • GENBANK/FJ931297
  • GENBANK/FJ931298
  • GENBANK/FJ931299
  • GENBANK/FJ931300
  • GENBANK/FJ931301
  • GENBANK/FJ931302
  • GENBANK/FJ931303
  • GENBANK/FJ931304
  • GENBANK/FJ931305
  • GENBANK/FJ931306
  • GENBANK/FJ931307
  • GENBANK/FJ931308
  • GENBANK/FJ931309
  • GENBANK/FJ931310
  • GENBANK/FJ931311
  • GENBANK/FJ931312
  • GENBANK/FJ931313
  • GENBANK/FJ931314
  • GENBANK/FJ931315
  • GENBANK/FJ931316
  • GENBANK/FJ931317
  • GENBANK/FJ931318
  • GENBANK/FJ931319
  • GENBANK/FJ931320
  • GENBANK/FJ931321
  • GENBANK/FJ931322
  • GENBANK/FJ931323
  • GENBANK/FJ931324
  • GENBANK/FJ931325
  • GENBANK/FJ931326
  • GENBANK/FJ931327
  • GENBANK/FJ931328
  • GENBANK/FJ931329
  • GENBANK/FJ931330
  • GENBANK/FJ931331
  • GENBANK/FJ931332
  • GENBANK/FJ931333
  • GENBANK/FJ931334
  • GENBANK/FJ931335
  • GENBANK/FJ931336
  • GENBANK/FJ931337
  • GENBANK/FJ931338
  • GENBANK/FJ931339
  • GENBANK/FJ931340
  • GENBANK/FJ931341
  • GENBANK/FJ931342
  • GENBANK/FJ931343
  • GENBANK/FJ931344
  • GENBANK/FJ931345
  • GENBANK/FJ931346
  • GENBANK/FJ931347
  • GENBANK/FJ931348
  • GENBANK/FJ931349
  • GENBANK/FJ931350
  • GENBANK/FJ931351
  • GENBANK/FJ931352
  • GENBANK/FJ931353
  • GENBANK/FJ931354
  • GENBANK/FJ931355
  • GENBANK/FJ931356
  • GENBANK/FJ931357
  • GENBANK/FJ931358
  • GENBANK/FJ931359
  • GENBANK/FJ931360
  • GENBANK/FJ931361
  • GENBANK/FJ931362
  • GENBANK/FJ931363
  • GENBANK/FJ931364
  • GENBANK/FJ931365
  • GENBANK/FJ931366
  • GENBANK/FJ931367
  • GENBANK/FJ931368
  • GENBANK/FJ931369
  • GENBANK/FJ931370
  • GENBANK/FJ931371
  • GENBANK/FJ931372
  • GENBANK/FJ931373
  • GENBANK/FJ931374
  • GENBANK/FJ931375
  • GENBANK/FJ931376
  • GENBANK/FJ931377
  • GENBANK/FJ931378
  • GENBANK/FJ931379
  • GENBANK/FJ931380
  • GENBANK/FJ931381
  • GENBANK/FJ931382
  • GENBANK/FJ931383
  • GENBANK/FJ931384
  • GENBANK/FJ931385
  • GENBANK/FJ931386
  • GENBANK/FJ931387
  • GENBANK/FJ931388
  • GENBANK/FJ931389
  • GENBANK/FJ931390
  • GENBANK/FJ931391
  • GENBANK/FJ931392
  • GENBANK/FJ931393
  • GENBANK/FJ931394
  • GENBANK/FJ931395
  • GENBANK/FJ931396
  • GENBANK/FJ931397
  • GENBANK/FJ931398
  • GENBANK/FJ931399
  • GENBANK/FJ931400
  • GENBANK/FJ931401
  • GENBANK/FJ931402
  • GENBANK/FJ931403
  • GENBANK/FJ931404
  • GENBANK/FJ931405
  • GENBANK/FJ931406
  • GENBANK/FJ931407
  • GENBANK/FJ931408
  • GENBANK/FJ931409
  • GENBANK/FJ931410
  • GENBANK/FJ931411
  • GENBANK/FJ931412
  • GENBANK/FJ931413
  • GENBANK/FJ931414
  • GENBANK/FJ931415
  • GENBANK/FJ931416
  • GENBANK/FJ931417
  • GENBANK/FJ931418
  • GENBANK/FJ931419
  • GENBANK/FJ931420
  • GENBANK/FJ931421
  • GENBANK/FJ931422
  • GENBANK/FJ931423
  • GENBANK/FJ931424
  • GENBANK/FJ931425
  • GENBANK/FJ931426
  • GENBANK/FJ931427
  • GENBANK/FJ931428
  • GENBANK/FJ931429
  • GENBANK/FJ931430
  • GENBANK/FJ931431
  • GENBANK/FJ931432
  • GENBANK/FJ931433
  • GENBANK/FJ931434
  • GENBANK/FJ931435
  • GENBANK/FJ931436
  • GENBANK/FJ931437
  • GENBANK/FJ931438
  • GENBANK/FJ931439
  • GENBANK/FJ931440
  • GENBANK/FJ931441
  • GENBANK/FJ931442
  • GENBANK/FJ931443
  • GENBANK/FJ931444
  • GENBANK/FJ931445
  • GENBANK/FJ931446
  • GENBANK/FJ931447
  • GENBANK/FJ931448
  • GENBANK/FJ931449
  • GENBANK/FJ931450
  • GENBANK/FJ931451
  • GENBANK/FJ931452
  • GENBANK/FJ931453
  • GENBANK/FJ931454
  • GENBANK/FJ931455
  • GENBANK/FJ931456
  • GENBANK/FJ931457
  • GENBANK/FJ931458
  • GENBANK/FJ931459
  • GENBANK/FJ931460