HIV and Infections Group, MRC Clinical Trials Unit, London, UK.
AIDS. 2010 Jul 31;24(12):1917-22. doi: 10.1097/QAD.0b013e32833c1d93.
Reduced replication capacity of viruses expressing drug resistant mutations implies that patients with transmitted drug resistance (TDR) could have lower HIV RNA viral load than those infected with wild-type virus.
We performed analysis using data from the UK HIV Drug Resistance Database and the UK CHIC study. Eligible patients had a resistance test performed between 1997 and 2007 while naive to antiretroviral therapy, were 16 years or older, and had a viral load and CD4 cell count measurement within 6 months of this test. Models were adjusted for CD4 cell count, viral subtype, ethnicity, risk group, sex, age, calendar year, clinical centre, and viral load assay.
Of a total of 7994 patients included, 709 (9%) had TDR: 604 (85%) had resistance to one drug class only [350 nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 164 non-nucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 90 protease inhibitors (PIs)], 77 (11%) to two classes (42 NRTIs/NNRTIs, 31 NRTIs/PIs, 4 NNRTIs/PIs), and 28 (4%) had resistance to all three classes. The overall mean (SD) viral load at the time of resistance testing was 4.60 (0.82) log(10) copies/ml, and did not differ by class of TDR. However, patients harbouring M184V/I (n = 61) had a significantly lower viral load [adjusted mean difference -0.33 log10 copies/ml (95% CI -0.54 to -0.11), 53% lower (95% CI 22 to 71%), P = 0.002] compared to wild-type virus.
Our study provides clear evidence of an in-vivo fitness cost associated with the M184V/I mutation independent of drug effects which select for this mutation. This was not observed for any other mutation, but true effects may have been obscured by reversion of initially resistant viruses to wild-type.
表达耐药突变的病毒复制能力降低意味着传播耐药（TDR）的患者的 HIV RNA 病毒载量可能低于感染野生型病毒的患者。
我们使用英国 HIV 耐药性数据库和英国 CHIC 研究的数据进行了分析。合格的患者在接受抗逆转录病毒治疗之前于 1997 年至 2007 年期间进行了耐药性检测，年龄在 16 岁及以上，并且在该检测后 6 个月内进行了病毒载量和 CD4 细胞计数测量。模型调整了 CD4 细胞计数、病毒亚型、种族、风险组、性别、年龄、日历年份、临床中心和病毒载量检测。
在总共 7994 名患者中，有 709 名（9%）患者存在 TDR：604 名（85%）仅对一种药物类别具有耐药性[350 种核苷（酸）逆转录酶抑制剂（NRTIs），164 种非核苷（酸）逆转录酶抑制剂（NNRTIs），90 种蛋白酶抑制剂（PIs）]，77 名（11%）对两种类别具有耐药性（42 种 NRTIs/NNRTIs，31 种 NRTIs/PIs，4 种 NNRTIs/PIs），28 名（4%）对所有三种类别具有耐药性。在耐药检测时，总体平均（SD）病毒载量为 4.60（0.82）log（10）拷贝/ml，与 TDR 类别无关。然而，携带 M184V/I（n = 61）的患者的病毒载量明显较低[调整后的平均差异-0.33 log10 拷贝/ml（95%CI-0.54 至-0.11），降低 53%（95%CI 22%至 71%），P = 0.002]，与野生型病毒相比。
我们的研究提供了明确的证据，表明 M184V/I 突变与药物效应无关的体内适应不良相关，该突变选择了这种突变。对于任何其他突变，我们都没有观察到这种情况，但最初耐药的病毒可能会恢复为野生型，这可能会掩盖真实的影响。
