Turriziani Ombretta, Russo Gianluca, Lichtner Miriam, Stano Armando, Tsague Giselle, Maida Paola, Vullo Vincenzo, Antonelli Guido
Department of Experimental Medicine, Virology Section, Sapienza University of Rome, Rome, Italy.
AIDS Res Hum Retroviruses. 2008 Jun;24(6):781-5. doi: 10.1089/aid.2007.0213.
The distribution of antiretroviral (ARV) therapy resistance mutations among HIV-1 strains was evaluated in 39 postpartum women, one pregnant woman, and 12 HIV-positive babies (seven newborns and five children) living in rural west Cameroon. Thirty-five women and all newborns received a single dose of nevirapine (NVP) to prevent mother-to-child transmission of HIV-1; two women were ARV treated and three were ARV naive. Of the 52 viral strains examined, three were subtype B, 45 were classified into eight HIV-1 non-B subtypes, and four remained unclassifiable. Sequence analysis for genotypic drug resistance in the reverse transcriptase (RT) gene showed the presence of mutations associated with nonnucleoside RT inhibitor resistance in 20% of the samples from NVP-treated women and in 57% of those from treated newborns. Mutations associated with nucleoside RT inhibitors (M184V in one case and V118I in four cases) were found in five samples, despite being derived from ARV-naive patients. As expected, a greater frequency of mutations was found in the protease gene region. Of the sequences analyzed, 79% harbored five to seven specific mutations. The secondary mutations showed the typical protease inhibitor resistance-associated pattern for non-subtype B viruses, M36I being the predominant mutation (92.5% in women, 100% in babies). Other mutations frequently detected were K20I, L63P, H69K, and I13V. These findings confirm that resistance mutations can be detected in ARV-naive patients infected with non-B subtypes and emphasize an urgent need for studies assessing the impact of these mutations on the efficacy of subsequent ARV therapy and on the appearance of drug-resistant strains.
在喀麦隆西部农村地区的39名产后妇女、1名孕妇以及12名HIV阳性婴儿（7名新生儿和5名儿童）中，评估了抗逆转录病毒（ARV）治疗耐药突变在HIV-1毒株中的分布情况。35名妇女和所有新生儿均接受了单剂量奈韦拉平（NVP）以预防HIV-1的母婴传播；2名妇女接受了ARV治疗，3名妇女未接受过ARV治疗。在所检测的52株病毒毒株中，3株为B亚型，45株被归类为8种HIV-1非B亚型，4株仍无法分类。对逆转录酶（RT）基因进行的基因型耐药序列分析显示，在接受NVP治疗的妇女样本中有20%、在接受治疗的新生儿样本中有57%存在与非核苷类RT抑制剂耐药相关的突变。在5个样本中发现了与核苷类RT抑制剂相关的突变（1例为M184V，4例为V118I），尽管这些样本来自未接受过ARV治疗的患者。正如预期的那样，在蛋白酶基因区域发现的突变频率更高。在分析的序列中，79%含有5至7个特定突变。继发突变显示出非B亚型病毒典型的蛋白酶抑制剂耐药相关模式，M36I是主要突变（在妇女中占92.5%，在婴儿中占100%）。其他经常检测到的突变有K20I、L63P、H69K和I13V。这些发现证实，在感染非B亚型的未接受过ARV治疗的患者中可检测到耐药突变，并强调迫切需要开展研究，评估这些突变对后续ARV治疗疗效以及耐药毒株出现的影响。
