Projected population-wide impact of antiretroviral therapy-linked isoniazid preventive therapy in a high-burden setting

Emily Kendall, Andrew Azman, Gary Maartens, Andrew Boulle, Robert J. Wilkinson, David Wesley Dowdy, Molebogeng X. Rangaka

Research output: Contribution to journalArticle

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 (TB)-HIV epidemic, calibrated to site-specific, historical epidemiologic and clinical trial data from Khayelitsha, South Africa. METHODS: We projected the 5-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) ART coverage, this ART-linked IPT intervention prevented one tuberculosis case per 18 [95% credible interval (CrI) 11-29] people treated. It lowered TB 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 TB 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 TB 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.

Original languageEnglish (US)
Pages (from-to)525-536
Number of pages12
JournalAIDS (London, England)
Volume33
Issue number3
DOIs
StatePublished - Mar 1 2019

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Isoniazid
Population
Tuberculosis
Therapeutics
Incidence
HIV
Numbers Needed To Treat

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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Projected population-wide impact of antiretroviral therapy-linked isoniazid preventive therapy in a high-burden setting. / Kendall, Emily; Azman, Andrew; Maartens, Gary; Boulle, Andrew; Wilkinson, Robert J.; Dowdy, David Wesley; Rangaka, Molebogeng X.

In: AIDS (London, England), Vol. 33, No. 3, 01.03.2019, p. 525-536.

Research output: Contribution to journalArticle

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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 (TB)-HIV epidemic, calibrated to site-specific, historical epidemiologic and clinical trial data from Khayelitsha, South Africa. METHODS: We projected the 5-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) ART coverage, this ART-linked IPT intervention prevented one tuberculosis case per 18 [95{\%} credible interval (CrI) 11-29] people treated. It lowered TB 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 TB 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 TB 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.",
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AU - Dowdy, David Wesley

AU - Rangaka, Molebogeng X.

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N2 - 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 (TB)-HIV epidemic, calibrated to site-specific, historical epidemiologic and clinical trial data from Khayelitsha, South Africa. METHODS: We projected the 5-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) ART coverage, this ART-linked IPT intervention prevented one tuberculosis case per 18 [95% credible interval (CrI) 11-29] people treated. It lowered TB 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 TB 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 TB 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.

AB - 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 (TB)-HIV epidemic, calibrated to site-specific, historical epidemiologic and clinical trial data from Khayelitsha, South Africa. METHODS: We projected the 5-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) ART coverage, this ART-linked IPT intervention prevented one tuberculosis case per 18 [95% credible interval (CrI) 11-29] people treated. It lowered TB 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 TB 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 TB 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.

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