Virological response to a triple nucleoside/nucleotide analogue regimen over 48 weeks in HIV-1-infected adults in Africa
Virological response to a triple nucleoside/nucleotide analogue regimen over 48 weeks in HIV-1-infected adults in Africa
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DOI：
10.1097/01.aids.0000233572.59522.45
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发表时间：
2006-06-26
期刊：
影响因子：
3.8
通讯作者：
Serwadda, D.
中科院分区：
文献类型：
--
作者：
Kaleebu, P.;Pillay, D.;Serwadda, D.
目的：为了评估病毒学反应长达48周，并出现在24周的HIV-1耐药突变，在治疗初治的成年人开始齐多夫定/拉米夫定/替诺福韦DF.Design：在DART trial.Methods内的队列：血浆HIV-1 RNA进行了测定，在300名成年人与基线CD 4细胞计数< 200细胞/μ l从网站在乌干达和津巴布韦使用罗氏Amplicor检测V1.5。结果：基线CD 4细胞计数中位数为101个细胞/μ l，HIV-1 RNA为279910个拷贝/ml（平均值为5.4 log（10））。48周时，61%（165/272）的HIV-1 RNA < 50和72%（196/272）< 400拷贝/ml，而24周时分别为59%（167/281）和79%（221/281）。在24周和48周，分别有15%和24%的HIV-1 RNA > 1000拷贝/ml（6%和17% > 10000拷贝/ml），平均CD 4细胞计数分别增加103和127个细胞/μ l。较高的基线CD 4细胞计数是48周时病毒学抑制的最重要预测因素，基线病毒载量的影响很小。来自第24周样本的HIV-1 RNA > 1000拷贝/ml的20种基因型中有18种显示逆转录酶的关键耐药突变。14例有M184 V [10例有1 - 4个额外的核苷类似物突变（NAM）]; 1例只有3个NAM;其余3例有K65 R。一名参与者与M184 V主要非核苷逆转录酶的突变相关，尽管没有公开的治疗与这类。结论：齐多夫定/拉米夫定/替诺福韦在晚期HIV疾病具有良好的病毒学疗效。在这些感染HIV-1亚型A、C或D的人群中，M184 V（有或无NAM）是最常见的耐药途径，而K65 R则较少被发现。(c)2006年利平科特威廉姆斯&威尔金斯。
Objectives: To evaluate virologic response up to 48 weeks, and emergence of HIV-1 resistance mutations at 24 weeks, in therapy-naive adults initiating zidovudine/lamivudine/tenofovir DF.Design: A cohort within the DART trial.Methods: Plasma HIV-1 RNA was assayed in 300 adults with baseline CD4 cell count < 200 cells/mu l from sites in Uganda and Zimbabwe using the Roche Amplicor assay v1.5. Samples with HIV-1 RNA > 1000 copies/ml at 24 weeks were sequenced in the pol region.Results: Median baseline CD4 cell count was 101 cells/mu l and HIV-1 RNA 279910copies/ml (mean, 5.4 log(10)). At 48 weeks, 61% (165/272) had HIV-1 RNA < 50 and 72% (196/272) < 400 copies/ml, compared with 59% (167/281) and 79% (221/281) at 24 weeks. At 24 and 48 weeks, 15 and 24% respectively had HIV-1 RNA > 1000 copies/ml (6 and 17% > 10000 copies/ml), and mean CD4 cell count increases were 103 and 127 cells/mu l, respectively. Higher baseline CD4 cell count was the most important predictor of virological suppression at 48 weeks, with little effect of baseline viral load. Eighteen of 20 genotypes from week 24 samples with HIV-1 RNA > 1000 copies/ml showed key resistance mutations in reverse transcriptase. Fourteen had M184V [10 with one to four additional nucleoside analogue mutations (NAMs)]; one had three NAMs only; and the remaining three had K65R. One participant with M184V had major non-nucleoside reverse transcriptase inhibitor-associated mutations, despite no disclosed treatment with this class.Conclusion: Zidovudine/lamivudine/tenofovir has good virological efficacy in advanced HIV disease. In this population, who were infected with HIV-1 subtypes A, C or D, M184V with or without NAMs was the most common route to resistance, whereas K65R was identified less often. (c) 2006 Lippincott Williams & Wilkins.