Balotta C, Berlusconi A, Pan A, Violin M, Riva C, Colombo M C, Gori A, Papagno L, Corvasce S, Mazzucchelli R, Facchi G, Velleca R, Saporetti G, Galli M, Rusconi S, Moroni M
Institute of Infectious and Tropical Diseases, L. Sacco Hospital, University of Milan, Italy.
Antivir Ther. 2000 Mar;5(1):7-14.
We retrospectively studied 38 Italian recently HIV-1-infected subjects who seroconverted from 1994 to 1997 to investigate: (i) the prevalence of nucleoside reverse transcriptase inhibitors (NRTI)-related mutations at primary infection; (ii) the proportion of naturally occurring mutations in reverse transcriptase (RT) and protease regions of patients naive for non-nucleoside RT inhibitors (NNRTIs) and protease inhibitors (PIs); (iii) the drug-susceptibility to NRTIs and PIs in subjects with NRTI- and/or PI-related mutations; and (iv) the outcome of seroconverters treated with various NRTIs or NRTI/PI regimens. Baseline HIV-1 plasma viraemia and absolute CD4 count at baseline could not be used to distinguish patients with NRTI- and/or PI-related pre-existing mutations from those with wild-type virus (P = 0.693 and P = 0.542, respectively). The frequency of zidovudine-related mutations was 21% in the study period. The response to treatment was not significantly different in subjects with or without genotypic zidovudine-related mutations at primary infection (P = 0.744 for HIV-1 RNA and P = 0.102 for CD4 cells). Some natural variation (2.6%) was present within regions 98-108 and 179-190 of RT involved in NNRTI resistance. The high natural polymorphism in the protease region present in our patients was similar to that reported by others. In our study some PI-associated substitutions, thought to be compensatory in protease enzymatic function, could confer intermediate to high PI-resistance. As discrepancies between genotypic and phenotypic results may exist in recent seroconverters, our data suggest that the role of transmitted NRTI- and PI-resistant variants remain to be fully elucidated in vivo.
我们回顾性研究了38名1994年至1997年期间发生血清转化的近期感染HIV-1的意大利受试者，以调查：（i）初次感染时核苷类逆转录酶抑制剂（NRTI）相关突变的发生率；（ii）未使用非核苷类逆转录酶抑制剂（NNRTI）和蛋白酶抑制剂（PI）的患者逆转录酶（RT）和蛋白酶区域自然发生突变的比例；（iii）具有NRTI和/或PI相关突变的受试者对NRTI和PI的药物敏感性；以及（iv）接受各种NRTI或NRTI/PI治疗方案的血清转化者的治疗结果。基线HIV-1血浆病毒血症和基线时的绝对CD4细胞计数无法用于区分具有NRTI和/或PI相关预先存在突变的患者与野生型病毒患者（分别为P = 0.693和P = 0.542）。在研究期间，齐多夫定相关突变的频率为21%。初次感染时具有或不具有基因型齐多夫定相关突变的受试者对治疗的反应无显著差异（HIV-1 RNA为P = 0.744，CD4细胞为P = 0.102）。在与NNRTI耐药相关的RT的98-108和179-190区域内存在一些自然变异（2.6%）。我们患者中蛋白酶区域存在的高自然多态性与其他人报告的相似。在我们的研究中，一些被认为对蛋白酶酶功能具有补偿作用的PI相关替代可能导致中等至高度的PI耐药性。由于近期血清转化者可能存在基因型和表型结果之间的差异，我们的数据表明，传播的NRTI和PI耐药变异体在体内的作用仍有待充分阐明。
