Diminished Representation of HIV-1 Variants Containing Select Drug Resistance-Conferring Mutations in Primary HIV-1 Infection

Diminished Representation of HIV-1 Variants Containing Select Drug Resistance-Conferring Mutations in Primary HIV-1 Infection
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原发性 HIV-1 感染中含有特定耐药性突变的 HIV-1 变异体的代表性减少

DOI:
10.1097/00126334-200412150-00017
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发表时间:
2004
期刊:
JAIDS Journal of Acquired Immune Deficiency Syndromes
影响因子:
--
通讯作者:
M. Wainberg
M. Wainberg
中科院分区:
--
文献类型:
--
作者:
D. Turner;B. Brenner;J. Routy;D. Moisi;Z. Rosberger;M. Roger;M. Wainberg

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本研究将在原发性 HIV 感染 (PHI) (n = 59) 中获得的携带胸苷类似物耐药性突变的 HIV-1 变异体的发生率,即胸苷类似物突变 (TAM)、非核苷逆转录酶 (RT) 抑制剂 (NNM)、拉米夫定 (3TC)(即 M184V)和蛋白酶抑制剂 (PI) 与相应潜在传播者中观察到的患病率(PT) 携带耐药感染的人群 (n = 380)。在该队列分析中,这两个人群都具有相似的人口统计特征。尽管 PT 组中观察到的 TAM、NNM、M184V 和蛋白酶相关突变 (PRAM) 的频率相似,但 PHI 组中 M184V 和主要 PI 突变的发生率显着较低(PHI/PT 比率分别为 0.14 和 0.39)。与在不存在 M184V 的情况下携带 NNM 或 TAM 的病毒相比,在 PHI 群体中,与 M184V 共表达 NNM 或 TAM 的耐药病毒的流行率降低 (P < 0.0001)。还观察到,PT 亚组中携带 RT 突变或带有 M184V 的 PRAM 的个体的血浆病毒血症水平低于缺乏 M184V 的个体(P < 0.05)。这些发现表明,在含有 M184V 的 HIV-1 变异体中,病毒血症和病毒适应性的降低可能会影响病毒的传播能力。
This study compared the incidence of HIV-1 variants harboring mutations conferring resistance to thymidine analogues, ie, thymidine analogue mutations (TAMs), nonnucleoside reverse transcriptase (RT) inhibitors (NNMs), lamivudine (3TC) (ie, M184V), and protease inhibitors (PIs) acquired in primary HIV infection (PHI) (n = 59) to their observed prevalence in a corresponding potential transmitter (PT) population of persons harboring resistant infections (n = 380). Both of these populations in the context of this cohort analysis possessed similar demographics. Whereas the frequencies of observed TAMs, NNMs, M184V, and protease-associated mutations (PRAMs) were similar in the PT groups, the prevalence of M184V and major PI mutations were significantly lower in the PHI group (PHI/PT ratios of 0.14 and 0.39, respectively). There was a decreased prevalence in the PHI population of resistant viruses co-expressing NNMs or TAMs with M184V compared with viruses that harbored NNMs or TAMs in the absence of M184V (P < 0.0001). It was also observed that individuals in the PT subgroups who harbored RT mutations or PRAMs with M184V had lower levels of plasma viremia than individuals who lacked M184V (P < 0.05). These findings suggest that both decreased viremia and viral fitness in the case of M184V-containing HIV-1 variants may impact on viral transmissibility.
DOI: 10.1128/jvi.73.10.8448-8456.1999
发表时间: 1999-10-01
影响因子: 5.4
作者:
Sharma, PL;Crumpacker, CS
通讯作者: Crumpacker, CS
DOI: 10.1056/nejmoa013552
发表时间: 2002-08-08
影响因子: 158.5
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发表时间: 2000-03-30
影响因子: 158.5
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