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分子多样性和治疗初治的喀麦隆晚期疾病患者中的 HIV-1 聚合酶基因基因型。

Molecular diversity and polymerase gene genotypes of HIV-1 among treatment-naïve Cameroonian subjects with advanced disease.

机构信息

Instituto Nacional de Câncer, Rio de Janeiro, Brazil.

出版信息

J Clin Virol. 2010 Jul;48(3):173-9. doi: 10.1016/j.jcv.2010.04.008. Epub 2010 May 18.

Abstract

BACKGROUND

The progress of antiretroviral treatment roll-out programs in developing countries requires extensive monitoring of primary drug resistance prior to initiation of therapy. This is particularly relevant for Cameroon where a high HIV diversity has been reported.

OBJECTIVES

To determine HIV diversity in Yaoundé, Cameroon, in a cohort of HIV-infected subjects with advanced disease. To characterize HIV-1 mutations conferring primary drug resistance and to assess primary resistance patterns in the RNase H domain of the reverse transcriptase of these viruses.

STUDY DESIGN

HIV-1 RNA was extracted from plasma of 59 HIV-1 infected, drug-naïve subjects with CD4+ T-cell counts<200/microl. HIV-1 pol (PR, RT and RNase H) regions were sequenced for subtyping and for identifying drug resistance mutations in pol (PR, RT and RNase H).

RESULTS

A complex HIV-1 diversity was seen, with multiple subtypes (A1, A2, C, D, F2, H, group O), CRFs (02_AG, 09_cpx, 11_cpx, 13_cpx, 22_01A1, 30_0206, 43_02G) and URFs. Primary drug resistance was low in PR (2%) and in RT regions (4%). RNase H mutations Q509L and Q547K were found in non-CRF02_AG strains.

CONCLUSIONS

A high HIV-1 diversity was already present in Cameroon in the early 90s, when the subjects were likely infected. Primary HIV-1 drug resistance was low. Occurrence of RNase H mutations with proven phenotypic effect on susceptibility to antiretrovirals encourages further assessment of their impact in treatment outcome in the context of complex HIV genetic diversity and in a subtype-specific fashion.

摘要

背景

发展中国家开展抗逆转录病毒治疗规划需要在开始治疗前广泛监测原发性耐药。这在喀麦隆尤为重要,因为这里报道了很高的 HIV 多样性。

目的

在雅温得的一组晚期 HIV 感染患者中确定 HIV 多样性。描述 HIV-1 突变引起的原发性耐药,并评估这些病毒逆转录酶 RNase H 区的原发性耐药模式。

研究设计

从 59 名 CD4+T 细胞计数<200/μl 的未经抗逆转录病毒药物治疗的 HIV-1 感染患者的血浆中提取 HIV-1 RNA。对 pol(PR、RT 和 RNase H)区进行 HIV-1 亚型鉴定和耐药突变分析。

结果

观察到复杂的 HIV-1 多样性,包括多种亚型(A1、A2、C、D、F2、H、O 组)、CRFs(02_AG、09_cpx、11_cpx、13_cpx、22_01A1、30_0206、43_02G)和 URFs。PR(2%)和 RT 区(4%)的原发性耐药率较低。在非 CRF02_AG 株中发现了 RNase H 突变 Q509L 和 Q547K。

结论

90 年代初,喀麦隆已经存在很高的 HIV-1 多样性,这些患者可能在此期间感染。原发性 HIV-1 耐药率较低。具有已证明对药物敏感性有表型影响的 RNase H 突变的发生,鼓励在复杂的 HIV 遗传多样性背景下,以及在亚型特异性的情况下,进一步评估其对治疗结果的影响。

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