Handema Ray, Terunuma Hiroshi, Kasolo Francis, Kasai Hirotake, Sichone Moses, Yamashita Atsuya, Deng Xuewen, Mulundu Georgina, Ichiyama Kouji, Munkanta Mwansa, Yokota Tomoyuki, Wakasugi Naomi, Tezuka Fumiaki, Yamamoto Naoki, Ito Masahiko
Department of Mircrobiology, Yamanashi Medical University, Tamaho, Japan.
AIDS Res Hum Retroviruses. 2003 Feb;19(2):151-60. doi: 10.1089/088922203762688667.
The ability of HIV-1 to evolve resistance to antiretroviral drugs leads to treatment failure. By nucleotide sequencing of HIV-1 subtype B isolates, amino acids responsible for drug resistance have been identified. Less information is available, however, on the extent and distribution of these amino acids in HIV-1 nonsubtype B viruses circulating mainly in developing countries. More HIV-infected patients in the developing world are now using antiretroviral drugs, and hence there is a need to monitor drug resistance mutations in HIV-1 non-subtype B viruses. This study examines the prevalence of drug resistance mutations in 28 antiretroviral drug-naive HIV-1-infected Zambians. HIV-1 proviral DNA was extracted from peripheral blood mononuclear cells. The region encompassing gag p17 to env C2-V3-C3 was amplified by the polymerase chain reaction followed by direct sequencing. Sequence analyses for drug resistance-associated mutations in th e protease and reverse transcriptase genes, and HIV-1 subtyping, were done. Overall, 92.8% of the generated sequences were HIV-1 subtype C. The generated sequences revealed only secondary associated, but no primary, drug-resistance mutations The most frequent secondary mutations in the protease and RT genes were, respectively, I93L(91.7%), L89M (79.2%), M3611V (79%, 4.2%), and R211K (70.8%), S48T (62.5%). The atypical residues M41N (3.6%) and D67A (3.6%) were detected in the RT gene. This study reveals many naturally occurring polymorphisms in HIV-1 subtype C isolates from antiretroviral drug-naive individuals. Such polymorphisms could lead to rapid treatment failure and development of drug-resistant HIV-1 mutants in individuals undergoing antiretroviral therapy.
人类免疫缺陷病毒1型（HIV-1）产生抗逆转录病毒药物耐药性的能力会导致治疗失败。通过对HIV-1 B亚型分离株进行核苷酸测序，已确定了与耐药性相关的氨基酸。然而，关于这些氨基酸在主要在发展中国家流行的HIV-1非B亚型病毒中的范围和分布，信息较少。现在，发展中世界有更多的HIV感染患者正在使用抗逆转录病毒药物，因此有必要监测HIV-1非B亚型病毒中的耐药性突变。本研究调查了28名未接受过抗逆转录病毒药物治疗的HIV-1感染赞比亚人中耐药性突变的流行情况。从外周血单个核细胞中提取HIV-1前病毒DNA。通过聚合酶链反应扩增包含gag p17至env C2-V3-C3的区域，随后进行直接测序。对蛋白酶和逆转录酶基因中与耐药性相关的突变进行序列分析，并进行HIV-1亚型分型。总体而言，所产生序列的92.8%为HIV-1 C亚型。所产生的序列仅显示出次要相关的耐药性突变，但没有主要耐药性突变。蛋白酶和逆转录酶基因中最常见的次要突变分别为I93L（91.7%）、L89M（79.2%）、M36I1V（79%、4.2%）以及R211K（70.8%）、S48T（62.5%）。在逆转录酶基因中检测到非典型残基M41N（3.6%）和D67A（3.6%）。本研究揭示了来自未接受过抗逆转录病毒药物治疗个体的HIV-1 C亚型分离株中存在许多自然发生的多态性。此类多态性可能导致正在接受抗逆转录病毒治疗的个体迅速出现治疗失败并产生耐药性HIV-1突变体。
