An observational study identifying highly tuberculosis-exposed, HIV-1-positive but persistently TB, tuberculin and IGRA negative persons with M. tuberculosis specific antibodies in Cape Town, South Africa

Background: Mycobacterium tuberculosis (Mtb) infection is inferred from positive results of T-cell immune conversion assays measuring Mtb-specific interferon gamma production or tuberculin skin test (TST) reactivity. Certain exposed individuals do not display T-cell immune conversion in these assays and do not develop TB. Here we report a hitherto unknown form of this phenotype: HIV-1-positive persistently TB, tuberculin and IGRA negative (HITTIN). Methods: A community-based case-control design was used to systematically screen and identify adults living with HIV (HIV+), aged 35–60 years, who met stringent study criteria, and then longitudinally followed up for repeat IGRA and TST testing. Participants had no history of TB despite living in TB hyper-endemic environments in Cape Town, South Africa with a provincial incidence of 681/100,000. Mtb-specific antibodies were measured using ELISA and Luminex. Findings: We identified 48/286 (17%) individuals who tested persistently negative for Mtb-specific T-cell immunoreactivity (three negative Quantiferon results and one TST = 0mm) over 206±154 days on average. Of these, 97·2% had documented CD4 counts<200 prior to antiretroviral therapy (ART). They had received ART for 7·0±3·0 years with a latest CD4 count of 505·8±191·4 cells/mm3. All HITTIN sent for further antibody testing (n=38) displayed  Mtb-specific antibody titres. Interpretation: Immune reconstituted HIV+ persons can be persistently non-immunoreactive to TST and interferon-γ T-cell responses to Mtb, yet develop species-specific antibody responses. Exposure is evidenced by Mtb-specific antibody titres. Our identification of HIV+ individuals displaying a persisting lack of response to TST and IGRA T-cell immune conversion paves the way for future studies to investigate this phenotype in the context of HIV-infection that so far have received only scant attention..

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:61

Enthalten in:

EBioMedicine - 61(2020), Seite 103053-

Sprache:

Englisch

Beteiligte Personen:

Elouise E. Kroon [VerfasserIn]
Craig J. Kinnear [VerfasserIn]
Marianna Orlova [VerfasserIn]
Stephanie Fischinger [VerfasserIn]
Sally Shin [VerfasserIn]
Sihaam Boolay [VerfasserIn]
Gerhard Walzl [VerfasserIn]
Ashley Jacobs [VerfasserIn]
Robert J. Wilkinson [VerfasserIn]
Galit Alter [VerfasserIn]
Erwin Schurr [VerfasserIn]
Eileen G. Hoal [VerfasserIn]
Marlo Möller [VerfasserIn]

Links:

doi.org [kostenfrei]
doaj.org [kostenfrei]
www.sciencedirect.com [kostenfrei]
Journal toc [kostenfrei]

Themen:

Antibodies
Early clearance
Interferon gamma release assay
Medicine
Medicine (General)
R
Resister
Tuberculin skin test

doi:

10.1016/j.ebiom.2020.103053

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

DOAJ053125339