Abstract
BackgroundThe risk of individuals infected with human immunodeficiency virus (HIV)-1 developing tuberculosis (TB) is high, while both prognostic and diagnostic tools remain insensitive. The potential for plasma biomarkers to predict which HIV-1–infected individuals are likely to progress to active disease is unknown.MethodsThirteen analytes were measured from QuantiFERON Gold in-tube (QFT) plasma samples in 421 HIV-1–infected persons recruited within the screening and enrollment phases of a randomized, controlled trial of isoniazid preventive therapy. Blood for QFT was obtained pre-randomization. Individuals were classified into prevalent TB, incident TB, and control groups. Comparisons between groups, supervised learning methods, and weighted correlation network analyses were applied utilizing the unstimulated and background-corrected plasma analyte concentrations.ResultsUnstimulated samples showed higher analyte concentrations in the prevalent and incident TB groups compared to the control group. The largest differences were seen for C-X-C motif chemokine 10 (CXCL10), interleukin-2 (IL-2), IL-1α, transforming growth factor-α (TGF-α). A predictive model analysis using unstimulated analytes discriminated best between the control and prevalent TB groups (area under the curve [AUC] = 0.9), reasonably well between the incident and prevalent TB groups (AUC > 0.8), and poorly between the control and incident TB groups. Unstimulated IL-2 and IFN-γ were ranked at or near the top for all comparisons, except the comparison between the control vs incident TB groups. Models using background-adjusted values performed poorly.ConclusionsSingle plasma biomarkers are unlikely to distinguish between disease states in HIV-1 co-infected individuals, and combinations of biomarkers are required. The ability to detect prevalent TB is potentially important, as no blood test hitherto has been suggested as having the utility to detect prevalent TB amongst HIV-1 co-infected persons.
Highlights
Single plasma biomarkers are unlikely to distinguish between disease states in human immunodeficiency virus (HIV)-1 co-infected individuals, and combinations of biomarkers are required
The role of isoniazid preventive therapy (IPT) to decrease the risk of TB in HIV-1–infected people is well-recognized [7]
A randomized, controlled trial (RCT) of IPT plus antiretroviral therapy (ART) versus ART alone for the prevention of TB in a large, well-characterized group of HIV-1–infected persons conducted in Khayelitsha, South Africa (ART-IPT Study), established that TST- or IGRA-negative, HIV-infected persons on ART benefit from IPT [8]
Summary
Thirteen analytes were measured from QuantiFERON Gold in-tube (QFT) plasma samples in 421 HIV-1–infected persons recruited within the screening and enrollment phases of a randomized, controlled trial of isoniazid preventive therapy. Individuals were classified into prevalent TB, incident TB, and control groups. A total of 421 persons were included in this analysis, based on IGRA sample availability at screening, and included 51 individuals who developed clinically- or microbiologically-confirmed TB during the 4-year duration of the study (incident TB). There were 283 controls with IGRA samples available and no signs or symptoms of TB during the duration of the follow-up (median duration of follow-up in the main study was 2.5 years), who were randomly chosen just before and just after the incident and prevalent cases in the order of recruitment. All samples used in the current analyses were collected before randomization
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