PLoS Comput Biol：艾滋病毒耐药性的起源问题

近日，哈佛大学的科学家们发现在少数艾滋病患者预先存在的突变可能导致病毒产生耐药性。这一发现特别重要，因为虽然研究人员早就知道艾滋病毒可以对某些药物产生耐药性，但我们一直不理解该病毒是否靠预先已经存在的突变来产生耐药性，相关研究论文发表在PLoS Computational Biology杂志上。

Pennings收集了26个临床试验的数据收集。这些患者接受NNRTI药物的治疗以阻止病毒的繁殖。然而她发现该病毒在接受治疗后的不久便会重新启动。

Pennings说：为了防止耐药性的发生，我们需要知道耐药突变都来自何处，弄明白这一点我们就可克服耐药这个难题。

这一发现表明预先存在的突变病毒会产生抗药性，这可能是早期疾病治疗的阻力所在。虽然这项研究结果给艾滋病治疗带来了新的希望，但Pennings强调在研究中使用的临床试验数据，只包含那些接受NNRTI或蛋白酶抑制剂治疗的患者。结果是否可以推广到其他病患的治疗目前还不清楚。（生物谷：Bioon.com）

doi:10.1371/journal.pcbi.1002527
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Pennings PS (2012) Standing Genetic Variation and the Evolution of Drug Resistance in HIV

Pleuni Simone Pennings

Drug resistance remains a major problem for the treatment of HIV. Resistance can occur due to mutations that were present before treatment starts or due to mutations that occur during treatment. The relative importance of these two sources is unknown. Resistance can also be transmitted between patients, but this process is not considered in the current study. We study three different situations in which HIV drug resistance may evolve: starting triple-drug therapy, treatment with a single dose of nevirapine and interruption of treatment. For each of these three cases good data are available from literature, which allows us to estimate the probability that resistance evolves from standing genetic variation. Depending on the treatment we find probabilities of the evolution of drug resistance due to standing genetic variation between and . For patients who start triple-drug combination therapy, we find that drug resistance evolves from standing genetic variation in approximately 6% of the patients. We use a population-dynamic and population-genetic model to understand the observations and to estimate important evolutionary parameters under the assumption that treatment failure is caused by the fixation of a single drug resistance mutation. We find that both the effective population size of the virus before treatment, and the fitness of the resistant mutant during treatment, are key-parameters which determine the probability that resistance evolves from standing genetic variation. Importantly, clinical data indicate that both of these parameters can be manipulated by the kind of treatment that is used.