The proportions of people living with HIV in low and middle-income countries who test tuberculin skin test positive using either a 5 mm or a 10 mm cut-off: a systematic review

BACKGROUND: A positive tuberculin skin test (TST) is often defined by skin induration of ≥10 mm in people who are HIV-seronegative. However, to increase sensitivity for detection of Mycobacterium tuberculosis infection in the context of impaired immune function, a revised cut-off of ≥5 mm is used for people living with HIV infection. The incremental proportion of patients who are included by this revised definition and the association between this proportion and CD4+ cell count are unknown. METHODS: The literature was systematically reviewed to determine the proportion of people living with HIV (PLWH) without evidence of active tuberculosis in low and middle-income countries who tested TST-positive using cut-offs of ≥5 mm and ≥10 mm of induration. The difference in the proportion testing TST-positive using the two cut-off sizes was calculated for all eligible studies and was stratified by geographical region and CD4+ cell count. RESULTS: A total of 32 studies identified meeting criteria were identified, providing data on 10,971 PLWH from sub-Saharan Africa, Asia and the Americas. The median proportion of PLWH testing TST-positive using a cut-off of ≥5 mm was 26.8% (IQR, 19.8-46.1%; range, 2.5-81.0%). Using a cut-off of ≥10 mm, the median proportion of PLWH testing TST-positive was 19.6% (IQR, 13.7-36.8%; range 0–52.1%). The median difference in the proportion of PLWH testing TST-positive using the two cut-offs was 6.0% (IQR, 3.4-10.1%; range, 0–37.6%). Among those with CD4+ cell counts of <200, 200–499 and ≥500 cells/μL, the proportion of positive tests defined by the ≥5 mm cut-off that were between 5.0 and 9.9 mm in diameter was similar (12.5%, 12.9% and 10.5%, respectively). CONCLUSIONS: There is a small incremental yield in the proportion of PLWH who test TST-positive when using an induration cut-off size of ≥5 mm compared to ≥10 mm. This proportion was similar across the range of CD4+ cell strata, supporting the current standardization of this cut-off at all levels of immunodeficiency.