Dykes Carrie, Demeter Lisa M
Infectious Diseases Division, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Clin Microbiol Rev. 2007 Oct;20(4):550-78. doi: 10.1128/CMR.00017-07.
The relative fitness of a variant, according to population genetics theory, is that variant's relative contribution to successive generations. Most drug-resistant human immunodeficiency virus type 1 (HIV-1) variants have reduced replication fitness, but at least some of these deficits can be compensated for by the accumulation of second-site mutations. HIV-1 replication fitness also appears to influence the likelihood of a drug-resistant mutant emerging during treatment failure and is postulated to influence clinical outcomes. A variety of assays are available to measure HIV-1 replication fitness in cell culture; however, there is no agreement regarding which assays best correlate with clinical outcomes. A major limitation is that there is no high-throughput assay that incorporates an internal reference strain as a control and utilizes intact virus isolates. Some retrospective studies have demonstrated statistically significant correlations between HIV-1 replication fitness and clinical outcomes in some patient populations. However, different studies disagree as to which clinical outcomes are most closely associated with fitness. This may be in part due to assay design, sample size limitations, and differences in patient populations. In addition, the strength of the correlations between fitness and clinical outcomes is modest, suggesting that, at present, it would be difficult to utilize these assays for clinical management.
根据群体遗传学理论，一个变异体的相对适合度是指该变异体对连续世代的相对贡献。大多数耐药的1型人类免疫缺陷病毒（HIV-1）变异体的复制适合度降低，但其中至少一些缺陷可通过第二位点突变的积累得到补偿。HIV-1复制适合度似乎也会影响治疗失败期间耐药突变体出现的可能性，并被推测会影响临床结果。有多种检测方法可用于测量细胞培养中HIV-1的复制适合度；然而，对于哪种检测方法与临床结果的相关性最佳，尚无共识。一个主要限制是，没有一种高通量检测方法能纳入内部参考菌株作为对照并使用完整的病毒分离株。一些回顾性研究表明，在某些患者群体中，HIV-1复制适合度与临床结果之间存在统计学上的显著相关性。然而，不同的研究对于哪些临床结果与适合度最密切相关存在分歧。这可能部分归因于检测设计、样本量限制以及患者群体的差异。此外，适合度与临床结果之间的相关性强度适中，这表明目前利用这些检测方法进行临床管理可能会很困难。
