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，在HIV-1感染个体中取得了较长时间的病毒复制抑制和临床疗效。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，而且对工业化国家未接受治疗的患者。这些耐多药病毒在没有治疗的患者中预计将在亚洲和非洲发展中国家传播，在这些国家，许多患者由于费用高昂而无法获得抗ads治疗的益处。这项研究的目的是显示在印度、巴基斯坦、越南和非洲肯尼亚的初次治疗患者的流行情况。据估计，印度感染艾滋病毒的患者人数是世界上最多的。对印度56例、巴基斯坦17例、越南13例和肯尼亚34例初治患者血清样本中的蛋白酶和逆转录酶（RT）编码区进行了分析。他们中没有发现对RT抑制剂的原发性耐药突变，但我们在1999年在印度发现了两名未接受治疗的个体，他们在蛋白酶区G48V和32A中有原发性耐药突变，据报道这些突变导致对沙基那韦、茚那韦和利托那韦的临床显著性反应丧失。其他样品对RT抑制剂和蛋白酶抑制剂的继发性耐药突变发生率较高（29 ~ 70%）。印度初次接受治疗的患者的原发性强耐药性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.