Sukasem C, Churdboonchart V, Chasombat S, Kohreanudom S, Watitpun C, Pasomsub E, Piroj W, Tiensuwan M, Chantratita W
Dept. of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Infection. 2007 Apr;35(2):81-8. doi: 10.1007/s15010-007-6169-x.
Due to the establishment of the National Access to Antiretroviral Program for People who have AIDS (NAPHA), approximately 80,000 Thai HIV-1 infected patients received antiretroviral drugs through the NAPHA program, which was completed at the end of 2005. The development of drug resistance is required for access to ARV drugs. The objective of this study was to determine the prevalence of antiretroviral drug resistance in Thai HIV-1 treated individuals after completing the NAPHA program.
Viral genotypic resistance testing was carried out for 1,880 HIV-infected patients experiencing treatment failure, who enrolled during 2000-2005. All patients were in a follow-up treatment with ARV drugs available in clinical practice. The genotype was performed with the TRUGENE HIV-1 kit to assess resistant mutations to reverse transcriptase inhibitors and to protease inhibitors.
The frequency of ARV drug resistance has significantly increased after the National Access To Antiretroviral Program was implemented. The reverse transcriptase genes M184V/I (919/1,880; 48.9%) and K103S/H (416/1,880; 22.1%) were the most frequent in nucleoside reverse transcriptase and non-nucleoside reverse transcriptase, respectively. In the protease genes, minor mutations or polymorphisms were found in the majority. Thymidine analogue mutations were presented and increased over time. This study showed a sharp increase in the prevalence of mutations associated with the GPO-VIR combination; nevirapine (948/1,880; 50.4%), lamivudine (889/1,880; 47.3%), and stavudine (703/1,880; 37.4%) after the program was completed.
With the increased availability of antiretroviral therapy in a resource-constrained country, antiretroviral drug resistance should be closely monitored. HIV-1 drug resistance testing to enable the salvage therapy will remain a priority in Thailand. Furthermore, resistance testing should also become routine before prescribing treatment, and the consequences of continuing to provide a failing regimen must be considered.
由于为艾滋病患者设立了国家抗逆转录病毒治疗项目(NAPHA),约8万名泰国HIV-1感染患者通过NAPHA项目接受了抗逆转录病毒药物治疗,该项目于2005年底结束。获得抗逆转录病毒药物需要了解耐药性的发展情况。本研究的目的是确定在完成NAPHA项目后,泰国接受HIV-1治疗的个体中抗逆转录病毒药物耐药性的流行情况。
对2000年至2005年期间登记的1880例治疗失败的HIV感染患者进行病毒基因型耐药性检测。所有患者均接受临床实践中可用的抗逆转录病毒药物的后续治疗。使用TRUGENE HIV-1试剂盒进行基因型检测,以评估对逆转录酶抑制剂和蛋白酶抑制剂的耐药突变。
在实施国家抗逆转录病毒治疗项目后,抗逆转录病毒药物耐药性的频率显著增加。在核苷类逆转录酶和非核苷类逆转录酶中,逆转录酶基因M184V/I(919/1880;48.9%)和K103S/H(416/1880;22.1%)最为常见。在蛋白酶基因中,大多数发现的是小突变或多态性。出现了胸苷类似物突变,且随时间增加。本研究表明,在项目完成后,与GPO-VIR组合相关的突变流行率急剧上升;奈韦拉平(948/1880;50.4%)、拉米夫定(889/1880;47.3%)和司他夫定(703/1880;37.4%)。
在一个资源有限的国家,随着抗逆转录病毒治疗可及性的提高,应密切监测抗逆转录病毒药物耐药性。进行HIV-1耐药性检测以实现挽救治疗在泰国仍将是优先事项。此外,在开处方治疗前,耐药性检测也应成为常规操作,并且必须考虑继续提供无效治疗方案的后果。