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HIV-1 Diversity and Drug Resistance Mutations among People Seeking HIV Diagnosis in Voluntary Counseling and Testing Sites in Rio de Janeiro Brazil

机译:在巴西里约热内卢的自愿咨询和检测点进行HIV诊断的人们中的HIV-1多样性和耐药性突变

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摘要

The remarkable viral diversity remains a big challenge to the development of HIV vaccines and optimal therapy worldwide. In the latest years, as a consequence of the large expansion of highly active antiretroviral therapy (HAART) availability worldwide, an increase in transmitted drug resistance mutations (TDRM) has been observed, varying according the region. This study assessed HIV-1 diversity and TDRM profile over time among newly HIV-1 diagnosed individuals from Rio de Janeiro, Brazil. Blood samples were collected from individuals seeking HIV diagnosis in four voluntary counseling and testing (VCTs) sites located in the Rio de Janeiro Metropolitan Area, in 2005–2007. Recent (RS) and long-term (LTS) HIV-1 seroconverters were distinguished using BED-CEIA. Pol viral sequences were obtained for 102 LTS identified in 2005 and 144 RS from 2005–2007. HIV-1 subtype and pol recombinant genomes were determined using Rega HIV-1 Subtyping Tool and by phylogenetic inferences and bootscanning analyses. Surveillance of HIV-1 TDRM to protease and reverse transcriptase inhibitors were performed according to the Calibrated Population Resistance (CPR) Tool 6.0. Overall, subtype B remains the most prevalent in Rio de Janeiro in both LTS and RS HIV-1 infected individuals. An increased proportion of recombinant samples was detected over time, especially in RS heterosexual men, due to the emergence of CRF02_AG and URF samples bearing a subtype K fragment. The prevalence of HIV-1 samples carrying TDRM was high and similar between LTS and RS (15.7% vs 14.6%) or age (<25yo 17.9% vs >25yo 16.6%) along the study period. The high resistance levels detected in both populations are of concern, especially considering the dynamics of HIV-1 diversity over time. Our results suggest that the incorporation of resistance testing prior to HAART initiation should be highly considered, as well as permanent surveillance, aiming to carefully monitoring HIV-1 diversity, with focus on CRF/URF emergence and putative transmission.
机译:显着的病毒多样性仍然是世界范围内开发HIV疫苗和最佳疗法的一大挑战。在最近几年中,由于高活性抗逆转录病毒疗法(HAART)在世界范围内的广泛使用,已观察到传播耐药性突变(TDRM)的增加,根据地区而异。这项研究评估了巴西里约热内卢新诊断为HIV-1的个体中HIV-1多样性和TDRM随时间的变化。 2005年至2007年,在里约热内卢都会区的四个自愿咨询和测试(VCT)地点从寻求HIV诊断的个体中采集血液样本。使用BED-CEIA可以区分最近的(RS)和长期的(LTS)HIV-1血清转换器。获得了2005年鉴定的102个LTS和2005-2007年鉴定的144个RS的Pol病毒序列。 HIV-1亚型和pol重组基因组是使用Rega HIV-1亚型分析工具以及系统发育推断和引导扫描分析确定的。根据校准的抗药性(CPR)工具6.0对HIV-1 TDRM对蛋白酶和逆转录酶抑制剂进行了监测。总体而言,无论是在LTS还是在RS HIV-1感染者中,B亚型在里约热内卢仍然是最普遍的。随着时间的推移,检测到重组样品的比例增加,尤其是在RS异性恋男性中,这是由于带有K型亚型片段的CRF02_AG和URF样品的出现。在整个研究期间,携带TDRM的HIV-1样本的患病率很高,在LTS和RS之间(15.7%对14.6%)或年龄(<25岁17.9%对> 25yo 16.6%)相似。在两个人群中检测到的高抗药性值得关注,特别是考虑到HIV-1多样性随时间的变化。我们的结果表明,应高度考虑在启动HAART之前进行耐药性检测以及永久性监测,以仔细监测HIV-1的多样性,重点是CRF / URF的出现和推定的传播。

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