Background
Current TB diagnostics are suboptimal to detect TB in patients with advanced HIV disease (AHD) who are at high risk for disseminated TB and mortality. Blood has been overlooked as a compartment for TB diagnostics in AHD. We determined the diagnostic yield of routine screening for TB in blood using Xpert Ultra (UXpert) and Myco/F Lytic (MFL) culture, and the utility of blood UXpert cycle threshold (Ct) and time to positivity (TTP) of MFL blood culture in predicting mortality.
Methods
We prospectively recruited adults with AHD (CD4 ≤100 or WHO stage 3 or 4) who were hospitalized for any reason at 3 hospitals in Vietnam. In addition to standard TB diagnostics (microscopy, UXpert and MGIT culture of non-blood specimens performed when clinically indicated), we screened all patients for TB in blood using UXpert and MFL culture. Patients were followed monthly over 6 months to determine TB outcome. We assessed the association of blood UXpert Ct value of the IS6110-1081 gene (CtIS) and TTP of MFL blood culture on 24-week mortality using Cox hazard models.
Results
Among 901 patients recruited between February 2021 and July 2023, 72 patients on active TB therapy were excluded. Among 829 patients, 83% were men. Median age was 36 years (IQR: 29-44). Median CD4 cell count was 18 (IQR: 8-43). 208 of 829 patients (25.1%) had microbiologically confirmed TB during the index hospitalization, and 10 developed TB during follow-up. Of these 208 TB patients, blood UXpert and MFL blood culture identified 151 cases (72.6%). This included 62 (30%) additional TB cases that were missed by the standard non-blood approach (Fig. 1A). Blood UXpert alone identified TB (and MDR TB) within 3 hours, enabling rapid initiation of TB therapy in 102 (49%) of 208 TB patients. The Cox models adjusted for sex, age, CD4 count identified the following independent predictors of 24-week mortality: (1) Positive TB in blood (mortality 32% vs. 12%, HR: 3.1, 95% CI:1.4-7, p <0.01) (Fig. 1B); (2) Blood UXpert CtIS ≤21 (mortality 50% vs. 24%, HR: 2.5, 95% CI: 1.2 – 5.1, p=0.016); (3) Faster TTP MFL blood culture (by one day) (HR: 1.06, 95% CI: 1.02–1.11, p= 0.01).
Conclusions
Among hospitalized patients with AHD, screening for TB in blood using currently available diagnostics of blood UXpert and MFL blood culture increased TB diagnostic yield by 30%. UXpert in blood alone made a rapid diagnosis of disseminated TB in 49% of TB patients, allowing rapid treatment and prognosis of patients.