Koizumi Yusuke, Ndembi Nicaise, Miyashita Michiko, Lwembe Raphael, Kageyama Seiji, Mbanya Dora, Kaptue Lazare, Numazaki Kei, Fujiyama Yoshihide, Ichimura Hiroshi
Department of Viral Infection and International Health, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
J Acquir Immune Defic Syndr. 2006 Sep;43(1):15-22. doi: 10.1097/01.qai.0000226793.16216.55.
The prevalence of antiretroviral therapy (ART) resistance-associated mutations among HIV-1 strains in western Cameroon was evaluated by genotypically analyzing strains isolated from drug-naive individuals. Proviral DNA was extracted from 54 blood samples and amplified by polymerase chain reaction of protease, reverse transcriptase, integrase, and envelope genes. At least 4 clones per sample were analyzed. Of 54 HIV-1 strains, 45 (83.3%) had a concordant subtype or circulating recombinant form (CRF) designation: 40 CRF02_AG, 2 subtype A1, 2 G, and 1 F2. The remaining 9 (16.7%) had a discordant subtype: 6 subtype A1/CRF02_AG, 2 D/CRF02, and 1 G/CRF02. Protease inhibitor-associated primary resistance mutations were found in 4 (7.4%) cases: M46L with full clones in 1 case, and M46I, M46L, and V82A as minor populations in 1 case each. Reverse transcriptase inhibitor-associated primary resistance mutations were found in 5 (9.8%) samples: Y188C in 2 cases, and L100I, M184V, and V75I in 1 case each, although all of these mutations were found as minor populations. This is one of the first reports of the emergence of primary ART resistance mutations among drug-naive, non-B subtype HIV-1-infected individuals in Cameroon. Follow-up studies should be conducted to assess whether these drug-resistant mutants found as minor populations might impact future ART.
通过对从未接受过治疗的个体分离出的毒株进行基因分型分析,评估了喀麦隆西部HIV-1毒株中抗逆转录病毒疗法(ART)耐药相关突变的流行情况。从54份血样中提取前病毒DNA,并通过蛋白酶、逆转录酶、整合酶和包膜基因的聚合酶链反应进行扩增。每个样本至少分析4个克隆。在54株HIV-1毒株中,45株(83.3%)具有一致的亚型或循环重组型(CRF):40株CRF02_AG、2株A1亚型、2株G亚型和1株F2亚型。其余9株(16.7%)具有不一致的亚型:6株A1/CRF02_AG、2株D/CRF02和1株G/CRF02。在4例(7.4%)中发现了蛋白酶抑制剂相关的原发性耐药突变:1例中M46L在完整克隆中出现,另外3例中M46I、M46L和V82A分别作为次要群体出现。在5份(9.8%)样本中发现了逆转录酶抑制剂相关的原发性耐药突变:2例中出现Y188C,另外3例中L100I、M184V和V75I分别各出现1例,不过所有这些突变均作为次要群体被发现。这是喀麦隆未接受过治疗、感染非B亚型HIV-1的个体中出现原发性ART耐药突变的首批报告之一。应开展后续研究,以评估这些作为次要群体发现的耐药突变体是否可能影响未来的ART治疗。