Aida Sivro1,2, Lyle R McKinnon1,2, Nonhlanhla Yende-Zuma1,3, Santhana Gengiah1, Natasha Samsunder1, Salim S Abdool Karim1,3,4, Kogieleum Naidoo1,3. 1. Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban. 2. Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada. 3. MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa. 4. Department of Epidemiology, Columbia University, New York.
Abstract
BACKGROUND: Immune correlates of tuberculosis (TB) risk in populations infected with human immunodeficiency virus (HIV) remain understudied, despite HIV being associated with a high burden of TB disease. Here we describe plasma cytokine correlates of TB recurrence in a well-characterized cohort of HIV-infected individuals on antiretroviral therapy (ART) with a history of prior TB cure. METHODS: Study participants were drawn from a prospective cohort study initiated at the conclusion of a randomized clinical trial in which individuals presented with untreated HIV infection and active pulmonary TB. At baseline, ART was initiated, and TB successfully cured. Participants were screened for TB recurrence quarterly for up to 4 years. TB recurrent cases (n = 63) were matched to controls (n = 123) on sex, study arm assignment in the original trial, and month of enrollment with a subset of cases sampled longitudinally at several time-points. RESULTS: Three cytokines were associated with increased rates of TB recurrence in univariate models: interleukin 6 (IL6) (odds ratio [OR] 2.66, 95% confidence interval [CI] 1.34-5.28, P = .005), IP10 (OR 4.62, 95% CI 1.69-12.65, P = .003), monokine induced by IFN-γ (MIG) (OR 3.11, 95% CI 1.10-8.82, P = .034). Conversely, interferon β (IFNβ) was associated with decreased TB risk (OR 0.34, 95% CI 0.13-0.87, P = .025). Following multivariate analyses adjusting for covariates IL6, interleukin 1β (IL1β), and interleukin 1Rα (IL1Rα) were associated with increased risk and IFNβ with decreased TB risk. Longitudinal analysis showed that levels of many TB-associated markers, including IL6, IP10, sCD14, and interferon γ (IFNγ) are reduced following TB treatment. CONCLUSION: These data show that TB recurrence, in HIV-infected individuals on ART is predicted by biomarkers of systemic inflammation, many of which are implicated in more rapid HIV disease progression. CLINICAL TRIALS REGISTRATION: NCT 01539005.
BACKGROUND: Immune correlates of tuberculosis (TB) risk in populations infected with human immunodeficiency virus (HIV) remain understudied, despite HIV being associated with a high burden of TB disease. Here we describe plasma cytokine correlates of TB recurrence in a well-characterized cohort of HIV-infected individuals on antiretroviral therapy (ART) with a history of prior TB cure. METHODS: Study participants were drawn from a prospective cohort study initiated at the conclusion of a randomized clinical trial in which individuals presented with untreated HIV infection and active pulmonary TB. At baseline, ART was initiated, and TB successfully cured. Participants were screened for TB recurrence quarterly for up to 4 years. TB recurrent cases (n = 63) were matched to controls (n = 123) on sex, study arm assignment in the original trial, and month of enrollment with a subset of cases sampled longitudinally at several time-points. RESULTS: Three cytokines were associated with increased rates of TB recurrence in univariate models: interleukin 6 (IL6) (odds ratio [OR] 2.66, 95% confidence interval [CI] 1.34-5.28, P = .005), IP10 (OR 4.62, 95% CI 1.69-12.65, P = .003), monokine induced by IFN-γ (MIG) (OR 3.11, 95% CI 1.10-8.82, P = .034). Conversely, interferon β (IFNβ) was associated with decreased TB risk (OR 0.34, 95% CI 0.13-0.87, P = .025). Following multivariate analyses adjusting for covariates IL6, interleukin 1β (IL1β), and interleukin 1Rα (IL1Rα) were associated with increased risk and IFNβ with decreased TB risk. Longitudinal analysis showed that levels of many TB-associated markers, including IL6, IP10, sCD14, and interferon γ (IFNγ) are reduced following TB treatment. CONCLUSION: These data show that TB recurrence, in HIV-infected individuals on ART is predicted by biomarkers of systemic inflammation, many of which are implicated in more rapid HIV disease progression. CLINICAL TRIALS REGISTRATION: NCT 01539005.
Authors: Tanuja N Gengiah; Nicholas H G Holford; Julia H Botha; Andrew L Gray; Kogieleum Naidoo; Salim S Abdool Karim Journal: Eur J Clin Pharmacol Date: 2011-11-23 Impact factor: 2.953
Authors: Netanya G Sandler; Handan Wand; Annelys Roque; Matthew Law; Martha C Nason; Daniel E Nixon; Court Pedersen; Kiat Ruxrungtham; Sharon R Lewin; Sean Emery; James D Neaton; Jason M Brenchley; Steven G Deeks; Irini Sereti; Daniel C Douek Journal: J Infect Dis Date: 2011-01-20 Impact factor: 5.226
Authors: Rachel P Simmons; Eileen P Scully; Erin E Groden; Kelly B Arnold; J Judy Chang; Kim Lane; Jeff Lifson; Eric Rosenberg; Douglas A Lauffenburger; Marcus Altfeld Journal: AIDS Date: 2013-10-23 Impact factor: 4.177
Authors: Matthew P R Berry; Christine M Graham; Finlay W McNab; Zhaohui Xu; Susannah A A Bloch; Tolu Oni; Katalin A Wilkinson; Romain Banchereau; Jason Skinner; Robert J Wilkinson; Charles Quinn; Derek Blankenship; Ranju Dhawan; John J Cush; Asuncion Mejias; Octavio Ramilo; Onn M Kon; Virginia Pascual; Jacques Banchereau; Damien Chaussabel; Anne O'Garra Journal: Nature Date: 2010-08-19 Impact factor: 49.962
Authors: Zuri A Sullivan; Emily B Wong; Thumbi Ndung'u; Victoria O Kasprowicz; William R Bishai Journal: EBioMedicine Date: 2015-04-01 Impact factor: 8.143
Authors: Stephanie Fischinger; Deniz Cizmeci; Sally Shin; Leela Davies; Patricia S Grace; Aida Sivro; Nonhlanhla Yende-Zuma; Hendrik Streeck; Sarah M Fortune; Douglas A Lauffenburger; Kogieleum Naidoo; Galit Alter Journal: Front Immunol Date: 2021-09-22 Impact factor: 7.561