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

Thorman, Johannes LU ; Björkman, Per LU orcid ; Marrone, Gaetano LU ; Balcha, Taye Tolera LU ; Tesfaye, Fregenet LU ; Abdissa, Tamene ; Naniche, Denise ; Medstrand, Patrik LU orcid and Reepalu, Anton LU orcid (2021) In Microbiology spectrum 9(3).
Abstract

Interferon-g-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),... (More)

Interferon-g-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-g-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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; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antiretroviral therapy, HIV, IP-10, Resource-limited settings, Tuberculosis, Viral load
in
Microbiology spectrum
volume
9
issue
3
article number
e01810
publisher
American Society for Microbiology
external identifiers
  • scopus:85122824715
  • pmid:34908450
ISSN
2165-0497
DOI
10.1128/SPECTRUM.01810-21
language
English
LU publication?
yes
id
a3b76914-069e-4135-a524-baea321c9047
date added to LUP
2022-03-10 15:16:53
date last changed
2024-06-13 11:25:43
@article{a3b76914-069e-4135-a524-baea321c9047,
  abstract     = {{<p>Interferon-g-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-g-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.</p>}},
  author       = {{Thorman, Johannes and Björkman, Per and Marrone, Gaetano and Balcha, Taye Tolera and Tesfaye, Fregenet and Abdissa, Tamene and Naniche, Denise and Medstrand, Patrik and Reepalu, Anton}},
  issn         = {{2165-0497}},
  keywords     = {{Antiretroviral therapy; HIV; IP-10; Resource-limited settings; Tuberculosis; Viral load}},
  language     = {{eng}},
  number       = {{3}},
  publisher    = {{American Society for Microbiology}},
  series       = {{Microbiology spectrum}},
  title        = {{Interferon-g-Inducible Protein 10 (IP-10) Kinetics after Antiretroviral Treatment Initiation in Ethiopian Adults with HIV}},
  url          = {{http://dx.doi.org/10.1128/SPECTRUM.01810-21}},
  doi          = {{10.1128/SPECTRUM.01810-21}},
  volume       = {{9}},
  year         = {{2021}},
}