异烟肼预防性治疗对抗逆转录病毒治疗的HIV感染者结核病发病率的治疗后效果。

Post-treatment effect of isoniazid preventive therapy on tuberculosis incidence in HIV-infected individuals on antiretroviral therapy.

作者信息

Sumner Tom, Houben Rein M G J, Rangaka Molebogeng X, Maartens Gary, Boulle Andrew, Wilkinson Robert J, White Richard G

机构信息

aDepartment of Infectious Disease Epidemiology, TB Modelling Group, TB Centre, Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine bDepartment of Infection and Population Health, Centre for Infectious Disease Epidemiology, University College London, London, UK cDepartment of Medicine, Institute of Infectious Disease and Molecular Medicine, University of Cape Town dDivision of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa eTuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA fCentre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa gDepartment of Medicine, Imperial College London hThe Francis Crick Institute Mill Hill Laboratory, London, UK iInstitute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.

出版信息

AIDS. 2016 May 15;30(8):1279-86. doi: 10.1097/QAD.0000000000001078.

DOI:10.1097/QAD.0000000000001078

PMID:26950316

Abstract

BACKGROUND

In HIV-uninfected individuals, isoniazid preventive therapy (IPT) has been associated with long-term protection against tuberculosis (TB). For HIV-infected/antiretroviral therapy (ART)-naive individuals, high TB rates have been observed following completion of IPT, consistent with a lack of 'cure' of infection. Recent trial data of IPT among HIV-infected individuals on ART in Khayelitsha, South Africa, have suggested that the effect of IPT persisted following completion of IPT.

METHODS

Using mathematical modelling, we explored if this increased duration of protection may be due to an increased curative ability of IPT when given in combination with ART. The model was used to estimate the annual risk of infection and proportion of individuals whose latent infection was 'cured' by IPT, defined such that they must be reinfected to be at risk of disease.

RESULTS

The estimated annual risk of infection was 4.0% (2.6-5.8) and the estimated proportion of individuals whose latent Mycobacterium tuberculosis infection was cured following IPT was 35.4% (2.4-76.4), higher than that previously estimated for HIV-infected/ART-naive individuals. Our results suggest that IPT can cure latent M. tuberculosis infection in approximately one-third of HIV-infected individuals on ART and therefore provide protection beyond the period of treatment.

CONCLUSION

Among HIV-infected individuals on ART in low incidence settings, 12 months of IPT may provide additional long-term benefit. Among HIV-infected individuals on ART in high incidence settings, the durability of this protection will be limited because of continued risk of reinfection, and continuous preventive therapy together with improved infection control efforts will be required to provide long-term protection against TB.

摘要

背景

在未感染艾滋病毒的个体中，异烟肼预防性治疗（IPT）与预防结核病（TB）的长期保护作用相关。对于未接受抗逆转录病毒治疗（ART）的艾滋病毒感染者，IPT完成后观察到高结核病发病率，这与感染未得到“治愈”一致。南非开普敦凯伊利沙地区对接受ART的艾滋病毒感染者进行IPT的近期试验数据表明，IPT完成后其效果仍持续存在。

方法

我们使用数学模型探讨了这种保护期延长是否可能是由于IPT与ART联合使用时其治愈能力增强。该模型用于估计年度感染风险以及IPT“治愈”潜伏感染的个体比例，这里将“治愈”定义为个体必须再次感染才会有患病风险。

结果

估计的年度感染风险为4.0%（2.6 - 5.8），IPT后潜伏结核分枝杆菌感染被治愈的个体估计比例为35.4%（2.4 - 76.4），高于先前对未接受ART的艾滋病毒感染者的估计比例。我们的结果表明，IPT可使约三分之一接受ART的艾滋病毒感染者的潜伏结核分枝杆菌感染得到治愈，因此在治疗期之后仍可提供保护。