Projected population-wide impact of antiretroviral therapy-linked isoniazid preventive therapy in a high-burden setting
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Supporting information
Accepted version
Author(s)
Type
Journal Article
Abstract
OBJECTIVE: Both isoniazid preventive therapy (IPT) and antiretroviral therapy (ART) reduce tuberculosis risk in individuals living with HIV. We sought to estimate the broader, population-wide impact of providing a pragmatically-implemented 12-month IPT regimen to ART recipients in a high-burden community. DESIGN: Dynamic transmission model of a tuberculosis-HIV epidemic, calibrated to site-specific, historical epidemiologic and clinical trial data from Khayelitsha, South Africa. METHODS: We projected the five-year impact of delivering a 12-month IPT regimen community-wide to 85% of new ART initiators and 15%/year of those already on ART, accounting for IPT-attributable reductions in TB infection, progression, and transmission. We also evaluated scenarios of continuously-delivered IPT, ongoing ART scale-up, and lower tuberculosis incidence. RESULTS: Under historical (early 2010 s) ART coverage, this ART-linked IPT intervention prevented one tuberculosis case per 18 (95% credible interval [CrI] 11-29) people treated. It lowered tuberculosis incidence by a projected 23% (95%CrI 14-30%) among people receiving ART, and by 5.2% (95%CrI 2.9-8.7%) in the total population. Continuous IPT reduced the number needed to treat to prevent one case of tuberculosis to 10 (95%CrI 7-16), though it required 74% more person-years of therapy (95%CrI 64-94%) to prevent one TB case, relative to 12-month therapy. Under expanding ART coverage, the tuberculosis incidence reduction achieved by 12-month IPT grew to 7.6% (95%CrI 4.3-12.6%). Effect sizes were similar in a simulated setting of lower tuberculosis incidence. CONCLUSIONS: IPT in conjunction with ART reduces tuberculosis incidence among those who receive therapy and has additional impact on tuberculosis transmission in the population.
Date Issued
2019-03-01
Date Acceptance
2018-09-21
Citation
AIDS, 2019, 33 (3), pp.525-536
ISSN
0269-9370
Publisher
Lippincott, Williams & Wilkins
Start Page
525
End Page
536
Journal / Book Title
AIDS
Volume
33
Issue
3
Copyright Statement
© 2018 Wolters Kluwer Health, Inc. This is a non-final version of an article published in final form in AIDS: October 15, 2018 - Publish Ahead of Print, https://dx.doi.org/10.1097/QAD.0000000000002053
Sponsor
Wellcome Trust
Wellcome Trust
Wellcome Trust
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30325773
Grant Number
072070/Z/03/Z
088316/Z/09/Z
104803/Z/14/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Infectious Diseases
Virology
Africa
antiretroviral therapy
latent tuberculosis
mathematical models
transmission
tuberculosis
tuberculosis prevention and control
HIV-INFECTED ADULTS
LATENT TUBERCULOSIS INFECTION
HUMAN-IMMUNODEFICIENCY-VIRUS
MIDDLE-INCOME COUNTRIES
CD4 CELL COUNTS
SHORT-TERM RISK
SOUTH-AFRICA
OPPORTUNISTIC INFECTIONS
DOUBLE-BLIND
FOLLOW-UP
Virology
06 Biological Sciences
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2018-10-15