Molecular Epidemiology of Drug Resistance of HIV in India, Pakistan and Vietnam

HIV-1逆转录酶和蛋白酶抑制剂联合化疗的进展使HIV-1感染者的病毒复制抑制期和临床疗效延长。然而，联合化疗导致的HIV-1耐药性的存在也产生了临床问题，不仅对接受治疗的患者，而且对工业化国家的初治患者。这些多重耐药病毒在未经治疗的患者中预计将在亚洲和非洲发展中国家传播，这些国家的许多患者由于费用高昂而无法获得抗ADS治疗的益处。本研究的目的是显示印度未经治疗的患者的患病率，印度的HIV感染患者估计人数被认为是世界上最多的，在巴基斯坦，越南和肯尼亚Aflica。蛋白酶和逆转录酶（RT）的编码区进行了分析，从56个治疗初治患者在印度，17个在巴基斯坦，13个在越南，34个在肯尼亚的血清样本。在这些患者中未发现对RT抑制剂的原发性耐药突变，但我们于1999年在印度确定了两名未接受过治疗的患者，他们在蛋白酶区域G48 V和32 A中存在原发性耐药突变，据报道，这些突变导致对沙奎那韦、茚地那韦和利托那韦的临床显著应答丧失。在其他样本中，对RT抑制剂和蛋白酶抑制剂的继发耐药突变率很高（29 ~ 70%），印度首次治疗患者的原发性强耐药突变的结果可能对通过联合国全球抗击艾滋病基金在发展中国家建立初始抗逆转录病毒治疗具有重要意义。

The progress of combination chemotherapy with HIV-1 reverse transcriptase and protease inhibitors has achieved a lengthen period of suppression of viral replication and clinical efficacy in HIV-1-infected individuals. Nevertheless, presence of HIV-1 resistance resulting from the combination chemotherapy also produces clinical problems, not only for the patients receiving therapy, but for treatment-nave patients in industrialized countries. These multiple-drug resistance viruses in treatment-nave patients are expected to spread m developing Asian and African countries, where lots of patients do not receive the benefit of anti-ADS treatments due to their high cost.It is the aim of this study to show the prevalence of treatment-naive patients in India, where the estimated number of HIV-infected-patients is considered to be the largest in the world, in Pakistan, Vietnam and Kenya Aflica. Protease and reverse transcriptase (RT) coding regions were analyzed in serum samples obtained from 56 treatment-naive patients in India, 17 in Pakistan, 13 in Vietnam, and 34 in Kenya. No primary resistance mutations to RT inhibitors were found among them, but we identified two treatment-naive individuals in 1999 in India, who have primary resistance mutations in protease region G48V and 32A which have been reported to result in a enhance clinically significant loss of response to Saquinavir, Indinavir and Ritonavir. There were high rate (29〜70%) secondaiy resistance mutations to RT inhibitors and Protease inhibitors in the other samples.The result of primary strong resistance mutations on therapy-naive patients in India may have important implications,in setting up initial antiretroviral therapy in developing countries via the United Nations' Global Fund to Fight AIDS.