Modeling the dynamic relationship between HIV and the risk of drug-resistant tuberculosis.
Modeling the dynamic relationship between HIV and the risk of drug-resistant tuberculosis.
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DOI：
10.1126/scitranslmed.3003815
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发表时间：
2012-05-23
影响因子：
17.1
通讯作者：
Cohen T
中科院分区：
文献类型：
--
作者：
Sergeev R;Colijn C;Murray M;Cohen T
高耐药结核病（TB）的出现以及结核病和艾滋病毒流行之间的相互作用给结核病控制带来了严峻挑战。先前的研究人员提出了几种假设，解释为什么与其他结核病患者相比，艾滋病毒合并感染的结核病患者患耐药结核病的风险可能更高。尽管一些研究发现个体的 HIV 状况与随后患耐多药结核病 (MDRTB) 的风险之间存在正相关关系，但观察到的 HIV 与耐药结核病之间的个体水平关系在不同环境中存在很大差异。在这里，我们开发了一个模型框架来探索艾滋病毒对耐药结核病动态的影响。该模型捕获了对重要类别结核病药物的耐药性的获得，施加与耐药性突变相关的适应度成本，并允许随后由于补偿突变而恢复适应度。尽管几个关键参数存在不确定性，但我们证明了流行病行为在一系列假设下都是稳健的。尽管几十年来艾滋病毒促进了社区内耐多药结核病的出现，但与直觉相反的是，患有结核病的艾滋病毒血清阳性个体在共流行的早期阶段患耐药结核病的风险可能较低。出现这种情况的原因是，许多艾滋病毒感染者在早期耐药性不太普遍的时期就已经感染了潜伏的结核分枝杆菌。我们发现，艾滋病毒的增加会增加人群中耐多药结核病的患病率，尽管与未受艾滋病毒影响的类似人群相比，它降低了流行的耐多药结核菌的平均适应度。 HIV 状况相似的个体之间的优先社会混合以及 HIV 血清阳性个体中平均 CD4 计数较低的情况进一步增加了预期的耐多药结核病负担。该模型表明，艾滋病毒与耐药结核病之间的个体水平关联是动态的，因此，未报告个体水平积极关联的横断面研究将无法保证艾滋病毒不会加剧社区耐药结核病的负担。
The emergence of highly drug-resistant tuberculosis (TB) and interactions between TB and HIV epidemics pose serious challenges for TB control. Previous researchers have presented several hypotheses for why HIV-coinfected TB patients may suffer an increased risk of drug-resistant TB compared to other TB patients. Although some studies have found a positive association between an individual’s HIV status and her subsequent risk of multidrug-resistant TB (MDRTB), the observed individual-level relationship between HIV and drug-resistant TB varies substantially among settings. Here, we develop a modeling framework to explore the effect of HIV on the dynamics of drug-resistant TB. The model captures the acquisition of resistance to important classes of TB drugs, imposes fitness costs associated with resistance-conferring mutations, and allows for subsequent restoration of fitness due to compensatory mutations. Despite uncertainty in several key parameters, we demonstrate epidemic behavior that is robust over a range of assumptions. Whereas HIV facilitates the emergence of MDRTB within a community over several decades, HIV-seropositive individuals presenting with TB may, counter-intuitively, be at lower risk of drug resistant TB at early stages of the co-epidemic. This situation arises because many individuals with incident HIV infection will already harbor latent Mycobacterium Tuberculosis infection acquired at an earlier time when drug-resistance was less prevalent. We find that the rise of HIV can increase the prevalence of MDRTB within populations even as it lowers the average fitness of circulating MDRTB strains compared to similar populations unaffected by HIV. Preferential social mixing among individuals with similar HIV-status and lower average CD4 counts among HIV-seropositive individuals further increase the expected burden of MDRTB. This model suggests that the individual-level association between HIV and drug-resistant forms of TB is dynamic and therefore cross-sectional studies that do not report a positive individual-level association will not provide assurance that HIV does not exacerbate the burden of resistant TB in the community.
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影响因子：
6.4
作者：
Brooks-Pollock, Ellen;Becerra, Mercedes C.;Murray, Megan B.
通讯作者：
Murray, Megan B.
由巨噬细胞诱导的外排机制介导的复制分枝杆菌的药物耐受性。
影响因子：
64.5
作者：
Adams KN;Takaki K;Connolly LE;Wiedenhoft H;Winglee K;Humbert O;Edelstein PH;Cosma CL;Ramakrishnan L
通讯作者：
Ramakrishnan L
影响因子：
6.4
作者：
Bifani, Pablo;Mathema, Barun;Kreiswirth, Barry N.
通讯作者：
Kreiswirth, Barry N.
影响因子：
1.4
作者：
Atun, RA;Lebcir, R;Coker, RJ
通讯作者：
Coker, RJ
影响因子：
82.9
作者：
Blower, SM;Chou, T
通讯作者：
Chou, T