Cardoso Ludimila Paula Vaz, Queiroz Boaventura Braz de, Stefani Mariane Martins de Araújo
Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia/Goiás, Brazil.
J Clin Virol. 2009 Oct;46(2):134-9. doi: 10.1016/j.jcv.2009.07.009. Epub 2009 Aug 13.
Primary resistance represents a challenge for the control of HIV-1 because it can reduce the efficacy of first line antiretroviral therapy and may impact clinical outcomes.
To describe the prevalence of primary HIV-1 drug resistance and subtypes circulating in Central West Brazil.
103 antiretroviral naïve patients were recruited in Goiânia city, Central West Brazil during 2007-2008. Protease and partial reverse transcriptase regions were retrotranscribed from plasma HIV-1 RNA and 97 were sequenced after direct nested PCR. HIV-1 subtype was assigned by phylogenetic analysis. Primary drug resistance was analyzed by the Calibrated Population Resistance (CPR) tool using Stanford Surveillance Drug Resistance Mutation (SDRM) and International AIDS Society-USA (IAS-USA) major mutation list.
Primary drug resistance mutations ranged from 8% (IAS) to 10% (SDRM). High level resistance to at least one antiretroviral drug was observed. T215D/S revertant mutations were identified in 4/97 patients. HIV-1 subtype B represented 82.5%, subtype F1 6.2%, subtype C 3.1%, B/F1 7.2% and one sample was a F1/C/B mosaic. HIV-1 subtype C sequences formed a monophyletic cluster with other Brazilian subtype C sequences.
Our HIV-1 pol sequences from Central West region include the first inland HIV-1 subtype C sequences and help compose the molecular epidemiology map of HIV-1 in Brazil. This data also show that a significant proportion of the naïve patients presented important drug resistance mutations. Therefore naive patients from this setting may benefit from pre-treatment genotypic testing to optimize the choice of antiretroviral drugs and to help control HIV-1 transmission.
原发性耐药是控制HIV-1面临的一项挑战,因为它会降低一线抗逆转录病毒疗法的疗效,并可能影响临床结局。
描述巴西中西部地区原发性HIV-1耐药情况及流行的亚型。
2007年至2008年期间,在巴西中西部的戈亚尼亚市招募了103例初治抗逆转录病毒治疗患者。从血浆HIV-1 RNA逆转录蛋白酶和部分逆转录酶区域,97例经直接巢式PCR后进行测序。通过系统发育分析确定HIV-1亚型。使用斯坦福监测耐药突变(SDRM)和美国国际艾滋病协会(IAS-USA)主要突变列表,通过校准群体耐药性(CPR)工具分析原发性耐药。
原发性耐药突变率在8%(IAS)至10%(SDRM)之间。观察到对至少一种抗逆转录病毒药物的高水平耐药。在4/97例患者中鉴定出T215D/S回复突变。HIV-1 B亚型占82.5%,F1亚型占6.2%,C亚型占3.1%,B/F1亚型占7.2%,一个样本为F1/C/B嵌合体。HIV-1 C亚型序列与其他巴西C亚型序列形成一个单系簇。
我们来自中西部地区的HIV-1 pol序列包括首批内陆HIV-1 C亚型序列,有助于构建巴西HIV-1的分子流行病学图谱。这些数据还表明,相当一部分初治患者存在重要的耐药突变。因此,来自该地区的初治患者可能受益于治疗前基因检测,以优化抗逆转录病毒药物的选择并有助于控制HIV-1传播。