Lihana Raphael W, Khamadi Samoel A, Lubano Kizito, Lwembe Raphael, Kiptoo Michael K, Lagat Nancy, Kinyua Joyceline G, Okoth Fredrick A, Songok Elijah M, Makokha Ernest P, Ichimura Hiroshi
Center for Virus Research, Kenya Medical Research Institute, Nairobi, Kenya.
AIDS Res Hum Retroviruses. 2009 Dec;25(12):1211-7. doi: 10.1089/aid.2009.0007.
The treatment of HIV-1 infection with antiretroviral drugs has greatly improved the survival of those who are infected. However, HIV-1 diversity and drug resistance are major challenges in patient management, especially in resource-poor countries. To evaluate HIV-1 genetic diversity and drug resistance-associated mutations among drug-naive patients in Kenya prior to antiretroviral therapy (ART), a genetic analysis of HIV-1 pol-RT and env-gp41 was performed on samples collected from 53 (18 males and 35 females) consenting patients between April and June 2005. The average age, baseline CD4(+) T cell counts, and viral loads were 38 (range, 24-62) years, 475 (range, 203-799) cells/mm(3), and 4.7 (range, 3.4-5.9) log(10) copies/ml, respectively. Phylogenetic analysis revealed that 40 samples (75.5%) were concordant subtypes for the two genes and 13 (24.5%) were discordant, suggesting possible recombination and/or dual infections. Prevalent subtypes included A1/A1(pol-RT/env-gp41), 31 (58.5%); D/D, 9 (16.9%); A1/C, 2 (3.8%); A1/D, 4 (7.5%); G/A1, 2 (3.8%); A1/A2, 1 (1.9%); C/A1, 2 (3.8%); D/A1, 1(1.9%); and D/A2, 1 (1.9%). Major reverse transcriptase inhibitor (RTI) resistance-associated mutations were found in four patients (7.5%). Of these patients, three had nucleoside RTI resistance mutations, such as M184V, K65R, D67N, K70R, and K219Q. Nonnucleoside RTI resistance-associated mutations K103N and Y181C were detected in three patients and one patient, respectively. Multiple drug resistance mutations were observed in this drug-naive population. With increasing numbers of patients that require treatment and the rapid upscaling of ART in Kenya, HIV-1 drug resistance testing is recommended before starting treatment in order to achieve better clinical outcomes.
使用抗逆转录病毒药物治疗HIV-1感染极大地提高了感染者的生存率。然而，HIV-1的多样性和耐药性是患者管理中的主要挑战，在资源匮乏的国家尤其如此。为了评估肯尼亚未接受过抗逆转录病毒治疗（ART）的初治患者中HIV-1的基因多样性和耐药相关突变，于2005年4月至6月对53名（18名男性和35名女性）同意参与的患者采集的样本进行了HIV-1 pol-RT和env-gp41的基因分析。平均年龄、基线CD4(+) T细胞计数和病毒载量分别为38岁（范围24 - 62岁）、475个细胞/mm³（范围203 - 799个细胞/mm³）和4.7 log₁₀拷贝/ml（范围3.4 - 5.9 log₁₀拷贝/ml）。系统发育分析显示，40个样本（75.5%）的两个基因亚型一致，13个样本（24.5%）不一致，提示可能存在重组和/或双重感染。流行的亚型包括A1/A1（pol-RT/env-gp41），31个样本（58.5%）；D/D，9个样本（16.9%）；A1/C，2个样本（3.8%）；A1/D，4个样本（7.5%）；G/A1，2个样本（3.8%）；A1/A2，1个样本（1.9%）；C/A1，2个样本（3.8%）；D/A1，1个样本（1.9%）；以及D/A2，1个样本（1.9%）。在4名患者（7.5%）中发现了主要的逆转录酶抑制剂（RTI）耐药相关突变。在这些患者中，3名患者有核苷类RTI耐药突变；如M184V、K⁶⁵R、D⁶⁷N、K⁷⁰R和K²¹⁹Q。非核苷类RTI耐药相关突变K103N和Y181C分别在3名患者和1名患者中检测到。在这个初治人群中观察到了多重耐药突变。随着肯尼亚需要治疗的患者数量增加以及ART的迅速推广，建议在开始治疗前进行HIV-1耐药检测，以获得更好的临床结果。
