Sensitivity of IFN-γ Release Assay to Detect Latent Tuberculosis Infection Is Retained in HIV-Infected Patients but Dependent on HIV/AIDS Progression

BACKGROUND: Detection and treatment of latent TB infection (LTBI) in HIV infected individuals is strongly recommended to decrease morbidity and mortality in countries with high levels of HIV. OBJECTIVE: To assess the validity of a newly developed in-house ELISPOT interferon-gamma release assay (IGRA) for the detection of LTBI amongst HIV infected individuals, in comparison with the Tuberculin Skin Test (TST). METHODOLOGY/PRINCIPAL FINDINGS: ESAT6/CFP10 (EC) ELISPOT assays were performed, together with a TST, in 285 HIV infected individuals recruited in HIV clinics in Dakar, Senegal, who had no signs of active TB at time of enrolment. Thirty eight of the subjects (13.3%) failed to respond to PHA stimulation and were excluded from the analysis. In the 247 remaining patients, response to PHA did not vary according to CD4 cell count categories (p = 0.51). EC ELISPOT was positive in 125 (50.6%) subjects, while 53 (21.5%) had a positive TST. Concordance between EC ELISPOT and TST was observed in 151 patients (61.1%) (kappa = 0.23). The proportion of subjects with a positive response to the EC ELISPOT assay decreased with declining CD4 counts (p trend = 0.001), but were consistently higher than the proportion of TST responders. In multivariate analysis, the risk of being EC-ELISPOT positive in HIV infected individuals was associated with age, CD4 count and HIV-1 strain. CONCLUSION: Our study indicates that IGRAs using M. tuberculosis specific antigens are likely to retain their validity for the diagnosis of LTBI among HIV positive individuals, but may be impaired by T-cell anergy in severely immuno-suppressed individuals

Characteristics of patients included in the cohort, with a detail of those responding and those not responding to ELISPOT PHA positive control.

*<p><i>p</i> value for difference between PHA<100 and PHA≥100 SFC/10⁶.</p

Distribution of responses to PHA and ESAT6/CFP10 ELISPOT assays in HIV patients, by CD4 cell count (boxplot showing median, IQR and range) (n = 285).

<p>1A: Distribution of responses to PHA. 1B: Distribution of responses to ESAT6/CFP10.</p

Analysis of the determinants of positive response to the ESAT6/CFP10 ELISPOT assay and to the TST (n = 247).

<p>Analysis of the determinants of positive response to the ESAT6/CFP10 ELISPOT assay and to the TST (n = 247).</p