Grossman Zehava, Istomin Valery, Averbuch Diana, Lorber Margalit, Risenberg Klaris, Levi Itzchak, Chowers Michael, Burke Michael, Bar Yaacov Nimrod, Schapiro Jonathan M
National HIV Reference Center, Central Virology Lab, Sheba Medical Center, Tel Hashomer 52621, Israel.
AIDS. 2004 Apr 9;18(6):909-15. doi: 10.1097/00002030-200404090-00008.
Genetic differences between subtypes of HIV-1, even when not associated with key resistance mutations, are known to affect baseline susceptibility to specific antiretroviral drugs and resistance-development pathways. We studied the prevalence and patterns of non-nucleoside reverse transcriptase inhibitor (NNRTI)-associated mutations in HIV-1 subtype C-infected patients.
We analysed the genetic variation at sites associated with NNRTI and nucleoside reverse transcriptase inhibitor resistance in subtype C- versus B-infected patients, both drug-naive and -experienced. We extended the comparison to subtype B records from the Stanford database.
A total of 150 subtype B and 341 subtype C-infected patients were studied. No significant differences were found in treatment and clinical parameters between the groups. In NNRTI-naive patients, changes in NNRTI positions were present in 9.3% of subtype B- versus 33.1% of subtype C-infected patients (P < 0.001). Differences were seen in both drug-naive (subtype B, 10.0% versus subtype C, 50.1%; P < 0.021) and drug-experienced NNRTI-naive patients (subtype B, 9.0% versus subtype C, 23.8%; P < 0.001). In NNRTI experienced patients, the number of A98G/S changes was significantly higher in subtype C patients treated with either efavirenz or nevirapine (P < 0.0001), and V106M was higher in efavirenz-treated subtype C-infected patients (P < 0.0001). The average mutation rates were 1.26 and 1.67 per patient for subtypes B and C, respectively (P = 0.036). The frequency of nucleoside associated mutations, but not M184V, in treated patients was significantly higher in subgroup B-infected patients (P = 0.028).
Collectively, these data indicate that genetic variation at NNRTI resistance-associated positions such as V106M and A98S is substantially greater in subtype C-infected patients than in subtype B-infected patients. The natural structure of each subtype probably affects the frequency and pattern of drug resistance mutations selected under treatment.
已知HIV-1各亚型之间的基因差异，即便与关键耐药突变无关，也会影响对特定抗逆转录病毒药物的基线易感性以及耐药性发展途径。我们研究了HIV-1 C亚型感染患者中与非核苷类逆转录酶抑制剂（NNRTI）相关突变的流行情况和模式。
我们分析了C亚型和B亚型感染患者（包括初治和经治患者）中与NNRTI及核苷类逆转录酶抑制剂耐药相关位点的基因变异情况。我们将比较范围扩展至斯坦福数据库中的B亚型记录。
共研究了150例B亚型和341例C亚型感染患者。两组在治疗和临床参数方面未发现显著差异。在初治NNRTI的患者中，B亚型感染患者NNRTI位点发生变化的比例为9.3%，而C亚型感染患者为33.1%（P < 0.001）。在初治患者（B亚型为10.0%，C亚型为50.1%；P < 0.021）和经治且初治NNRTI的患者（B亚型为9.0%，C亚型为23.8%；P < 0.001）中均观察到差异。在经治NNRTI的患者中，接受依非韦伦或奈韦拉平治疗的C亚型患者中A98G/S变化的数量显著更高（P < 0.0001），而接受依非韦伦治疗的C亚型感染患者中V106M变化更高（P < 0.0001）。B亚型和C亚型患者的平均突变率分别为每位患者1.26和1.67（P = 0.036）。在接受治疗的患者中，B亚型感染患者核苷类相关突变的频率显著更高，但M184V突变频率无显著差异（P = 0.028）。
总体而言，这些数据表明，在与NNRTI耐药相关的位点如V106M和A98S处，C亚型感染患者的基因变异比B亚型感染患者大得多。各亚型的天然结构可能会影响治疗过程中选择的耐药突变的频率和模式。
