Molecular Evolution and Systematics Laboratory, Zoology, Ryan Institute, School of Natural Sciences, National University of Ireland, Galway, Ireland.
AIDS Res Ther. 2011 Oct 13;8(1):38. doi: 10.1186/1742-6405-8-38.
Drug resistance testing before initiation of, or during, antiretroviral therapy (ART) is not routinely performed in resource-limited settings. High levels of viral resistance circulating within the population will have impact on treatment programs by increasing the chances of transmission of resistant strains and treatment failure. Here, we investigate Drug Resistance Mutations (DRMs) from blood samples obtained at regular intervals from patients on ART (Baseline-22 months) in Karonga District, Malawi. One hundred and forty nine reverse transcriptase (RT) consensus sequences were obtained via nested PCR and automated sequencing from blood samples collected at three-month intervals from 75 HIV-1 subtype C infected individuals in the ART programme.
Fifteen individuals showed DRMs, and in ten individuals DRMs were seen from baseline samples (reported to be ART naïve). Three individuals in whom no DRMs were observed at baseline showed the emergence of DRMs during ART exposure. Four individuals who did show DRMs at baseline showed additional DRMs at subsequent time points, while two individuals showed evidence of DRMs at baseline and either no DRMs, or different DRMs, at later timepoints. Three individuals had immune failure but none appeared to be failing clinically.
Despite the presence of DRMs to drugs included in the current regimen in some individuals, and immune failure in three, no signs of clinical failure were seen during this study. This cohort will continue to be monitored as part of the Karonga Prevention Study so that the long-term impact of these mutations can be assessed. Documenting proviral population is also important in monitoring the emergence of drug resistance as selective pressure provided by ART compromises the current plasma population, archived viruses can re-emerge.
在开始或进行抗逆转录病毒治疗 (ART) 之前，资源有限的环境中通常不进行耐药性检测。人群中循环的高病毒耐药水平将通过增加耐药株传播和治疗失败的机会，对治疗方案产生影响。在此，我们调查了马拉维卡拉翁加地区接受 ART（基线-22 个月）的患者定期从血液样本中获得的耐药突变 (DRMs)。从接受 ART 方案的 75 名 HIV-1 亚型 C 感染者的血液样本中，通过嵌套 PCR 和自动测序，每三个月收集一次，共获得 149 个逆转录酶 (RT) 共识序列。
15 名个体显示出耐药突变，其中 10 名个体在基线样本中观察到耐药突变（报告为对 ART 无反应）。在基线时未观察到耐药突变的 3 名个体在接受 ART 暴露期间出现耐药突变。在基线时显示耐药突变的 4 名个体在随后的时间点显示出额外的耐药突变，而 2 名个体在基线时显示出耐药突变，随后的时间点则没有耐药突变或不同的耐药突变。3 名个体出现免疫失败，但均无临床失败迹象。
尽管一些个体的当前方案药物存在耐药突变，并且 3 名个体免疫失败，但在本研究期间未观察到临床失败迹象。这一队列将继续作为卡拉翁加预防研究的一部分进行监测，以便评估这些突变的长期影响。记录前病毒群体对于监测耐药性的出现也很重要，因为 ART 提供的选择性压力会削弱当前的血浆群体，已存档的病毒可能会重新出现。
