Sepúlveda-Torres Lycely Del C, Rishishwar Lavanya, Rogers Maria Luisa, Ríos-Olivares Eddy, Boukli Nawal, Jordan I King, Cubano Luis A
Department of Microbiology and Immunology, Universidad Central del Caribe, Bayamón, Puerto Rico, United States of America.
School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
PLoS One. 2017 May 11;12(5):e0177452. doi: 10.1371/journal.pone.0177452. eCollection 2017.
Puerto Rico has one of the highest rates of HIV/AIDS seen for any US state or territory, and antiretroviral therapy has been a mainstay of efforts to mitigate the HIV/AIDS public health burden on the island. We studied the evolutionary dynamics of HIV-1 mutation and antiretroviral drug resistance in Puerto Rico by monitoring the population frequency of resistance-associated mutations from 2002 to 2011. Whole blood samples from 4,475 patients were analyzed using the TRUGENE HIV-1 Genotyping Kit and OpenGene DNA Sequencing System in the Immunoretrovirus Research Laboratory at Universidad Central del Caribe. Results show that 64.0% of female and 62.9% of male patients had HIV-1 mutations that confer resistance to at least one antiretroviral medication. L63P and M184V were the dominant mutations observed for the protease (PRO) and reverse transcriptase (RT) encoding genes, respectively. Specific resistance mutations, along with their associated drug resistance profiles, can be seen to form temporal clusters that reveal a steadily changing landscape of resistance trends over time. Both women and men showed resistance mutations for an average of 4.8 drugs over the 10-year period, further underscoring the strong selective pressure exerted by antiretrovirals along with the rapid adaptive response of HIV. Nevertheless, both female and male patients showed a precipitous decrease for overall drug resistance, and for PRO mutations in particular, over the entire course of the study, with the most rapid decrease in frequency seen after 2006. The reduced HIV-1 mutation and drug resistance trends that we observed are consistent with previous reports from multi-year studies conducted around the world. Reduced resistance can be attributed to the use of more efficacious antiretroviral drug therapy, including the introduction of multi-drug combination therapies, which limited the ability of the virus to mount rapid adaptive responses to antiretroviral selection pressure.
波多黎各是美国所有州或领地中艾滋病毒/艾滋病感染率最高的地区之一，抗逆转录病毒疗法一直是减轻该岛艾滋病毒/艾滋病公共卫生负担努力的主要手段。我们通过监测2002年至2011年耐药相关突变的人群频率，研究了波多黎各艾滋病毒-1突变和抗逆转录病毒药物耐药性的进化动态。在加勒比中央大学的免疫逆转录病毒研究实验室，使用TRUGENE艾滋病毒-1基因分型试剂盒和OpenGene DNA测序系统对4475名患者的全血样本进行了分析。结果显示，64.0%的女性患者和62.9%的男性患者携带艾滋病毒-1突变，这些突变使他们对至少一种抗逆转录病毒药物产生耐药性。L63P和M184V分别是蛋白酶（PRO）编码基因和逆转录酶（RT）编码基因中观察到的主要突变。特定的耐药突变及其相关的耐药谱可以看出形成了时间簇，揭示了随着时间推移耐药趋势不断变化的情况。在这10年期间，男性和女性患者平均对4.8种药物表现出耐药突变，这进一步凸显了抗逆转录病毒药物施加的强大选择压力以及艾滋病毒的快速适应性反应。然而，在整个研究过程中，女性和男性患者的总体耐药性，特别是PRO突变，都急剧下降，2006年后频率下降最为迅速。我们观察到的艾滋病毒-1突变和耐药性趋势的降低与世界各地多年研究的先前报告一致。耐药性降低可归因于使用了更有效的抗逆转录病毒药物疗法，包括引入多药联合疗法，这限制了病毒对抗逆转录病毒选择压力做出快速适应性反应的能力。
