HIV-1 reverse transcriptase drug-resistance mutations in chronically infected individuals receiving or naïve to HAART in Cameroon.

HIV-1 reverse transcriptase drug-resistance mutations in chronically infected individuals receiving or naïve to HAART in Cameroon.
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DOI:
10.1002/jmv.21677
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发表时间:
2010-02
影响因子:
12.7
通讯作者:
Nyambi, Phillipe N.
Nyambi, Phillipe N.
中科院分区:
医学3区
文献类型:
--
作者:
Burda, Sherri T.;Viswanath, Ragupathy;Zhao, Jiangqin;Kinge, Thompson;Anyangwe, Christopher;Tinyami, Erick T.;Haldar, Bijayesh;Powell, Rebecca L. R.;Jarido, Veronica;Hewlett, Indira K.;Nyambi, Phillipe N.

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在喀麦隆,HIV-1感染者接受的最常见的一线高效抗逆转录病毒治疗(HAART)是Triomune联合疗法,由两种核苷逆转录酶抑制剂(NRTI)和一种非NRTI(NNRTI)组成。为了检查这些药物在喀麦隆的疗效,其中多种非B HIV-1亚型和重组病毒占主导地位,对患者血浆中的逆转录酶(RT)病毒序列进行了分析,以确定是否存在耐药性突变。从喀麦隆西南部和西北部地区的艾滋病毒/艾滋病门诊诊所接受治疗的人中随机选择了49名艾滋病毒1型阳性者。在接受HAART治疗的28例患者中,39%(11/28)对NRTI耐药,46%(13/28)对NNRTI耐药,中位时间为治疗开始后12个月。在有耐药突变的患者中,HAART治疗开始后的中位时间为14个月,而没有耐药突变的患者为9个月;平均病毒载量没有差异(10,997拷贝/ml vs. 8,056拷贝/ml)。相比之下,药物初治个体的平均病毒载量(27,929拷贝/ml)显著高于接受HAART的个体(9,527拷贝/ml)。引人注目的是,在21名未接受过药物治疗的人中,24%携带有耐药性突变的病毒,这表明HIV-1耐药性变体正在喀麦隆传播。鉴于一线HAART患者中耐药突变的频率很高,再加上未接受过药物治疗的个体中具有耐药突变的HIV-1变异体的高流行率,本研究强调需要广泛监测耐药突变并在喀麦隆引入二线HAART策略。
The most common first-line, highly active anti-retroviral therapy (HAART) received by individuals infected with HIV-1 in Cameroon is the combination therapy Triomune, comprised of two nucleoside reverse transcriptase inhibitors (NRTI) and one non-NRTI (NNRTI). To examine the efficacy of these drugs in Cameroon, where diverse non-B HIV-1 subtypes and recombinant viruses predominate, the reverse transcriptase (RT) viral sequences in patient plasma were analyzed for the presence of mutations that confer drug resistance. Forty-nine HIV-1-positive individuals were randomly selected from those receiving care in HIV/AIDS outpatient clinics in the South-West and North-West Regions of Cameroon. Among the 28 patients receiving HAART, 39% (11/28) had resistance to NRTIs, and 46% (13/28) to NNRTIs after a median of 12 months from the start of therapy. Among those with drug-resistance mutations, there was a median of 14 months from the start of HAART, versus 9 months for those without; no difference was observed in the average viral load (10,997 copies/ml vs. 8,056 copies/ml). In contrast, drug-naïve individuals had a significantly higher average viral load (27,929 copies/ml) than those receiving HAART (9,527 copies/ml). Strikingly, among the 21 drug-naïve individuals, 24% harbored viruses with drug-resistance mutations, suggesting that HIV-1 drug-resistant variants are being transmitted in Cameroon. Given the high frequency of resistance mutations among those on first-line HAART, coupled with the high prevalence of HIV-1 variants with drug-resistance mutations among drug-naïve individuals, this study emphasizes the need for extensive monitoring of resistance mutations and the introduction of a second-line HAART strategy in Cameroon.
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