Interferon-γ-Inducible Protein 10 (IP-10) Kinetics after Antiretroviral Treatment Initiation in Ethiopian Adults with HIV

ABSTRACT Interferon-γ-inducible protein 10 (IP-10) has been suggested as a marker for targeted viral load (VL) monitoring during antiretroviral treatment (ART). We aimed to determine the kinetics of IP-10 during the initial year of ART, with particular regard to the impact of tuberculosis (TB) co-in...

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Main Authors: Johannes Thorman, Per Björkman, Gaetano Marrone, Taye Tolera Balcha, Fregenet Tesfaye, Tamene Abdissa, Denise Naniche, Patrik Medstrand, Anton Reepalu
Format: Article
Language:English
Published: American Society for Microbiology 2021-12-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/Spectrum.01810-21
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author Johannes Thorman
Per Björkman
Gaetano Marrone
Taye Tolera Balcha
Fregenet Tesfaye
Tamene Abdissa
Denise Naniche
Patrik Medstrand
Anton Reepalu
author_facet Johannes Thorman
Per Björkman
Gaetano Marrone
Taye Tolera Balcha
Fregenet Tesfaye
Tamene Abdissa
Denise Naniche
Patrik Medstrand
Anton Reepalu
author_sort Johannes Thorman
collection DOAJ
description ABSTRACT Interferon-γ-inducible protein 10 (IP-10) has been suggested as a marker for targeted viral load (VL) monitoring during antiretroviral treatment (ART). We aimed to determine the kinetics of IP-10 during the initial year of ART, with particular regard to the impact of tuberculosis (TB) co-infection on IP-10 secretion. Longitudinal plasma IP-10 levels were quantified in 112 treatment-naive HIV-positive adults at Ethiopian health centers, through enzyme-linked immunosorbent assay (ELISA) using samples obtained before and during the initial 12 months of ART. All participants underwent bacteriological TB investigation before starting ART. In virological responders (VRs; defined as VL < 150 copies/ml with no subsequent VL ≥ 1,000 copies/ml), IP-10 kinetics were analyzed using linear regression models. Among 91/112 (81.3%) participants classified as VRs, 17 (18.7%) had concomitant TB. Median baseline IP-10 was 650 pg/ml (interquartile range [IQR], 428–1,002) in VRs. IP-10 decline was more rapid during the first month of ART (median 306 pg/ml/month) compared with later time intervals (median 7-48 pg/ml/month, P < 0.001 in each comparison). Although VRs with TB had higher IP-10 levels at baseline (median 1106 pg/ml [IQR, 627–1,704]), compared with individuals without TB (median 628 pg/ml [IQR, 391–885]; P = 0.003), the rate of IP-10 decline during ART was similar, regardless of TB-status. During the initial year of ART, IP-10 kinetics followed a biphasic pattern in VRs, with a more rapid decline in the first month of ART compared with later time intervals. Baseline IP-10 was higher in individuals with TB versus individuals without TB, but the kinetics during ART were similar. IMPORTANCE To reach the goal of elimination of HIV as public health threat, access to antiretroviral treatment (ART) has to be further scaled up. To ensure viral suppression in individuals receiving ART, novel and robust systems for treatment monitoring are required. Targeting viral load monitoring to identify individuals at increased likelihood of treatment failure, using screening tools, could be an effective use of limited resources for viral load testing. Interferon-γ-inducible protein 10 (IP-10), a host inflammation mediator, has shown potential for this purpose. Here, we have investigated IP-10 kinetics in Ethiopian adults with HIV during the initial year after ART initiation. IP-10 levels decreased in parallel with viral load during ART, and prevalent tuberculosis at ART initiation did not influence IP-10 kinetics. This study shows satisfactory performance for IP-10 as a surrogate marker for viral load in persons starting ART, with no influence of concomitant tuberculosis.
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spelling doaj.art-18242ed626e140b888557b10ebc5fc102022-12-21T19:35:36ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972021-12-019310.1128/Spectrum.01810-21Interferon-γ-Inducible Protein 10 (IP-10) Kinetics after Antiretroviral Treatment Initiation in Ethiopian Adults with HIVJohannes Thorman0Per Björkman1Gaetano Marrone2Taye Tolera Balcha3Fregenet Tesfaye4Tamene Abdissa5Denise Naniche6Patrik Medstrand7Anton Reepalu8Clinical Infection Medicine, Department of Translational Medicine, Lund University, Malmö, SwedenClinical Infection Medicine, Department of Translational Medicine, Lund University, Malmö, SwedenDepartment of Global Public Health, Karolinska Institutet, Stockholm, SwedenClinical Infection Medicine, Department of Translational Medicine, Lund University, Malmö, SwedenClinical Infection Medicine, Department of Translational Medicine, Lund University, Malmö, SwedenAdama Public Health Research and Referral Laboratory Center, Adama, EthiopiaInstituto de Salud Global de Barcelona (ISGlobal) Hospital Clinic, University of Barcelona, Barcelona, SpainClinical Virology, Department of Translational Medicine, Lund University, Malmö, SwedenClinical Infection Medicine, Department of Translational Medicine, Lund University, Malmö, SwedenABSTRACT Interferon-γ-inducible protein 10 (IP-10) has been suggested as a marker for targeted viral load (VL) monitoring during antiretroviral treatment (ART). We aimed to determine the kinetics of IP-10 during the initial year of ART, with particular regard to the impact of tuberculosis (TB) co-infection on IP-10 secretion. Longitudinal plasma IP-10 levels were quantified in 112 treatment-naive HIV-positive adults at Ethiopian health centers, through enzyme-linked immunosorbent assay (ELISA) using samples obtained before and during the initial 12 months of ART. All participants underwent bacteriological TB investigation before starting ART. In virological responders (VRs; defined as VL < 150 copies/ml with no subsequent VL ≥ 1,000 copies/ml), IP-10 kinetics were analyzed using linear regression models. Among 91/112 (81.3%) participants classified as VRs, 17 (18.7%) had concomitant TB. Median baseline IP-10 was 650 pg/ml (interquartile range [IQR], 428–1,002) in VRs. IP-10 decline was more rapid during the first month of ART (median 306 pg/ml/month) compared with later time intervals (median 7-48 pg/ml/month, P < 0.001 in each comparison). Although VRs with TB had higher IP-10 levels at baseline (median 1106 pg/ml [IQR, 627–1,704]), compared with individuals without TB (median 628 pg/ml [IQR, 391–885]; P = 0.003), the rate of IP-10 decline during ART was similar, regardless of TB-status. During the initial year of ART, IP-10 kinetics followed a biphasic pattern in VRs, with a more rapid decline in the first month of ART compared with later time intervals. Baseline IP-10 was higher in individuals with TB versus individuals without TB, but the kinetics during ART were similar. IMPORTANCE To reach the goal of elimination of HIV as public health threat, access to antiretroviral treatment (ART) has to be further scaled up. To ensure viral suppression in individuals receiving ART, novel and robust systems for treatment monitoring are required. Targeting viral load monitoring to identify individuals at increased likelihood of treatment failure, using screening tools, could be an effective use of limited resources for viral load testing. Interferon-γ-inducible protein 10 (IP-10), a host inflammation mediator, has shown potential for this purpose. Here, we have investigated IP-10 kinetics in Ethiopian adults with HIV during the initial year after ART initiation. IP-10 levels decreased in parallel with viral load during ART, and prevalent tuberculosis at ART initiation did not influence IP-10 kinetics. This study shows satisfactory performance for IP-10 as a surrogate marker for viral load in persons starting ART, with no influence of concomitant tuberculosis.https://journals.asm.org/doi/10.1128/Spectrum.01810-21HIVantiretroviral therapyviral loadtuberculosisIP-10resource-limited settings
spellingShingle Johannes Thorman
Per Björkman
Gaetano Marrone
Taye Tolera Balcha
Fregenet Tesfaye
Tamene Abdissa
Denise Naniche
Patrik Medstrand
Anton Reepalu
Interferon-γ-Inducible Protein 10 (IP-10) Kinetics after Antiretroviral Treatment Initiation in Ethiopian Adults with HIV
Microbiology Spectrum
HIV
antiretroviral therapy
viral load
tuberculosis
IP-10
resource-limited settings
title Interferon-γ-Inducible Protein 10 (IP-10) Kinetics after Antiretroviral Treatment Initiation in Ethiopian Adults with HIV
title_full Interferon-γ-Inducible Protein 10 (IP-10) Kinetics after Antiretroviral Treatment Initiation in Ethiopian Adults with HIV
title_fullStr Interferon-γ-Inducible Protein 10 (IP-10) Kinetics after Antiretroviral Treatment Initiation in Ethiopian Adults with HIV
title_full_unstemmed Interferon-γ-Inducible Protein 10 (IP-10) Kinetics after Antiretroviral Treatment Initiation in Ethiopian Adults with HIV
title_short Interferon-γ-Inducible Protein 10 (IP-10) Kinetics after Antiretroviral Treatment Initiation in Ethiopian Adults with HIV
title_sort interferon γ inducible protein 10 ip 10 kinetics after antiretroviral treatment initiation in ethiopian adults with hiv
topic HIV
antiretroviral therapy
viral load
tuberculosis
IP-10
resource-limited settings
url https://journals.asm.org/doi/10.1128/Spectrum.01810-21
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