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首页> 外文期刊>AIDS Research and Human Retroviruses >Genotypic impact of prolonged detectable HIV type 1 RNA viral load after HAART failure in a CRF01_AE-infected cohort.
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Genotypic impact of prolonged detectable HIV type 1 RNA viral load after HAART failure in a CRF01_AE-infected cohort.

机译：在CRF01_AE感染的队列中进行HAART失败后，可检测的HIV 1型RNA病毒载量延长的基因型影响。

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摘要

HIV subtype-specific data on mutation type, rate, and accumulation following HAART treatment failure are limited. We studied patterns and accrual of drug resistance mutations in a Cambodian CRF01_AE-infected cohort continuing a virologically failing first-line, nonnucleoside reverse transcriptase inhibitor- (NNRTI-) based, HAART. Between 2005 and 2007, 837 adult HIV-infected patients had regular plasma HIV-1 RNA viral load measurements at Sihanouk Hospital Centre of Hope (SHCH), Cambodia. Drug resistance testing was performed in all patients with HIV-1 RNA >1000 copies/ml after at least 6 months of HAART. Seventy-one patients with a mean age of 34 years, of whom 68% were male, were retrospectively assessed at virological failure. The median duration of antiretroviral therapy was 12.3 (IQR 7.1-18.23) months, the median CD4 cell count was 173 (IQR 118-256) cells/mm(3), and the mean plasma HIV-1 RNA viral load was 3.9 log (SD 0.72) at failure. NNRTI mutations, M184I/V mutation, thymidine analogue mutations, and K65R were observed in 78.9%, 69%, 20%, and 12.7% of patients, respectively. For 33 patients, genotypic testing was carried out on at least two occasions before the switch to second-line HAART after a median duration of 5.8 (IQR 4.3-6.1) months of virological failure: 54.5% of patients accumulated new mutations with a rate of 1.6 mutations per person-year. Accumulation was seen both for nucleoside and nonnucleoside reverse transcriptase inhibitors, and also in patients with low-level viremia. Subtype-specific data on mutation type, rate, and accumulation after HAART failure are urgently needed to optimize treatment strategies in resource-limited settings.
机译：在HAART治疗失败后，有关突变类型，发生率和积累的HIV亚型特异性数据有限。我们研究了在柬埔寨CRF01_AE感染的队列中继续发生病毒学失败的一线，非核苷逆转录酶抑制剂（NNRTI-）的HAART的耐药性突变的模式和累积。在2005年至2007年之间，柬埔寨西哈努克希望医院中心（SHCH）对837名成人HIV感染患者进行了定期的血浆HIV-1 RNA病毒载量测量。至少经过6个月的HAART治疗后，对所有HIV-1 RNA> 1000拷贝/ ml的患者进行了耐药性测试。回顾性评估了平均年龄为34岁的71例患者，其中68％为男性。抗逆转录病毒疗法的中位持续时间为12.3（IQR 7.1-18.23）个月，中位数CD4细胞计数为173（IQR 118-256）细胞/ mm（3），平均血浆HIV-1 RNA病毒载量为3.9 log（ SD 0.72）失败。分别在78.9％，69％，20％和12.7％的患者中观察到NNRTI突变，M184I / V突变，胸苷类似物突变和K65R。对于33例患者，在病毒学中位数为5.8（IQR 4.3-6.1）个月的中位病程后，在切换到二线HAART之前至少进行了两次基因型测试：54.5％的患者积累了新突变，突变率为每人年1.6个突变。在核苷和非核苷逆转录酶抑制剂以及低病毒血症患者中均发现了积累。迫切需要有关HAART失败后突变类型，发生率和积累的亚型特定数据，以在资源有限的环境中优化治疗策略。

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