@article{Kroon2020,
abstract = {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{\`{A}}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 {\S}154 days on average. Of these, 97¢2{\%} had documented CD4 counts{\textless}200 prior to antiretroviral therapy (ART). They had received ART for 7¢0 {\S}3¢0 years with a latest CD4 count of 505¢8 {\S}191¢4 cells/mm 3. 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-g 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.},
author = {Kroon, Elouise E and Kinnear, Craig J and Orlova, Marianna and Fischinger, Stephanie and Shin, Sally and Boolay, Sihaam and Walzl, Gerhard and Jacobs, Ashley and Wilkinson, Robert J and Alter, Galit and Schurr, Erwin and Hoal, Eileen G and M{\"{o}}ller, Marlo},
doi = {10.1016/j.ebiom.2020.103053},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Kroon et al. - 2020 - An observational study identifying highly tuberculosis-exposed, HIV-1-positive but persistently TB, tuberculin and.pdf:pdf},
issn = {23523964},
journal = {EBioMedicine},
keywords = {Antibodies,Early clearance,Interferon gamma release assay,OA,Resister,Tuberculin skin test,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {nov},
pages = {103053},
pmid = {33038764},
publisher = {Elsevier},
title = {{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}},
url = {https://linkinghub.elsevier.com/retrieve/pii/S2352396420304291},
volume = {61},
year = {2020}
}

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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 35À60 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\\textless200 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/mm 3. 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-g 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.","author":[{"propositions":[],"lastnames":["Kroon"],"firstnames":["Elouise","E"],"suffixes":[]},{"propositions":[],"lastnames":["Kinnear"],"firstnames":["Craig","J"],"suffixes":[]},{"propositions":[],"lastnames":["Orlova"],"firstnames":["Marianna"],"suffixes":[]},{"propositions":[],"lastnames":["Fischinger"],"firstnames":["Stephanie"],"suffixes":[]},{"propositions":[],"lastnames":["Shin"],"firstnames":["Sally"],"suffixes":[]},{"propositions":[],"lastnames":["Boolay"],"firstnames":["Sihaam"],"suffixes":[]},{"propositions":[],"lastnames":["Walzl"],"firstnames":["Gerhard"],"suffixes":[]},{"propositions":[],"lastnames":["Jacobs"],"firstnames":["Ashley"],"suffixes":[]},{"propositions":[],"lastnames":["Wilkinson"],"firstnames":["Robert","J"],"suffixes":[]},{"propositions":[],"lastnames":["Alter"],"firstnames":["Galit"],"suffixes":[]},{"propositions":[],"lastnames":["Schurr"],"firstnames":["Erwin"],"suffixes":[]},{"propositions":[],"lastnames":["Hoal"],"firstnames":["Eileen","G"],"suffixes":[]},{"propositions":[],"lastnames":["Möller"],"firstnames":["Marlo"],"suffixes":[]}],"doi":"10.1016/j.ebiom.2020.103053","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Kroon et al. - 2020 - An observational study identifying highly tuberculosis-exposed, HIV-1-positive but persistently TB, tuberculin and.pdf:pdf","issn":"23523964","journal":"EBioMedicine","keywords":"Antibodies,Early clearance,Interferon gamma release assay,OA,Resister,Tuberculin skin test,fund_ack,original","mendeley-tags":"OA,fund_ack,original","month":"nov","pages":"103053","pmid":"33038764","publisher":"Elsevier","title":"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","url":"https://linkinghub.elsevier.com/retrieve/pii/S2352396420304291","volume":"61","year":"2020","bibtex":"@article{Kroon2020,\r\nabstract = {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{\\`{A}}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 {\\S}154 days on average. 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