Comparing interferon-gamma release assays to tuberculin skin test in Thai children with tuberculosis exposure.

BACKGROUND: Data on the performance of interferon-gamma release assays (IGRAs), QuantiFERON TB Gold In-tube (QFNGIT) and T-Spot.TB, in diagnosing tuberculosis (TB) are limited in Southeast Asia. This study aims to compare the performances of the two IGRAs and TST in Thai children with recent TB exposure. METHODS: This multicenter, prospective study enrolled children with recent exposure to active TB adults. Children were investigated for active TB. TST was performed and blood collected for T-Spot.TB and QFNGIT. RESULTS: 158 children were enrolled (87% TB-exposed and 13% active TB, mean age 7.2 years). Only 3 children had HIV infection. 66.7% had TST≥10 mm, while 38.6% had TST≥15 mm. 32.5% had positive QFNGIT; 29.9% had positive T-Spot.TB. QFNGIT and T-Spot.TB positivity was higher among children with active TB compared with TB-exposed children. No indeterminate IGRA results were detected. No statistically significant differences between the performances of the IGRAs and TST at the two cut-offs with increasing TB exposure were detected. Concordance for positive IGRAs and TST ranged from 42-46% for TST≥10 mm and 62-67% for TST≥15 mm. On multivariable analyses, exposure to household primary/secondary caregiver with TB was associated with positive QFNGIT. Higher TB contact score and active TB were associated with positive T-Spot.TB. CONCLUSIONS: Both QFNGIT and T-Spot.TB performed well in our Thai pediatric study population. No differences in the performances between tests with increasing TB exposure were found. Due to accessibility and low cost, using TST may more ideal than IGRAs in diagnosing latent and active TB in healthy children in Thailand and other similar settings.

A 72-week randomized study of the safety and efficacy of a stavudine to zidovudine switch at 24 weeks compared to zidovudine or tenofovir disoproxil fumarate when given with lamivudine and nevirapine.

BACKGROUND: Due to superior long-term toxicity profiles, zidovudine (AZT) and tenofovir disoproxil fumarate (TDF) are preferred over stavudine (d4T) for first-line antiretroviral regimens. However, short-term d4T use could be beneficial in avoiding AZT-induced anaemia. METHODS: We randomized (1:1:1) 150 treatment-naive Thai HIV-infected adults with CD4(+) T-cell count <350 cells/mm(3) to arm 1 (24-week GPO-VIR S30(®) [d4T plus lamivudine (3TC) plus nevirapine (NVP)] followed by 48-week GPO-VIR Z250(®) [AZT plus 3TC plus NVP]), arm 2 (72-week GPO-VIR Z250(®)) or arm 3 (72-week TDF plus emtricitabine [FTC] plus NVP). Haemoglobin (Hb), dual energy x-ray absorptiometry, neuropathic signs, estimated glomerular filtration rate (eGFR), CD4(+) T-cell count, plasma HIV RNA and adherence were assessed. RESULTS: In an intention-to-treat analysis, mean Hb decreased from baseline to week 24 in arm 2 compared with arm 1 (-0.19 versus 0.68 g/dl; P=0.001) and arm 3 (0.48 g/dl; P=0.010). Neuropathic signs were more common in arm 2 compared with arm 3 (20.4 versus 4.2%; P=0.028) at week 24. There were no differences in changes in peripheral fat and eGFR from baseline to weeks 24 and 72 among arms. CD4(+) T-cell count increased more in arm 1 than arms 2 and 3 from baseline to week 24 (168 versus 117 and 118 cells/mm(3); P=0.01 and 0.02, respectively) but the increase from baseline to week 72 was similar among arms. CONCLUSIONS: A 24-week d4T lead-in therapy caused less anaemia and greater initial CD4(+) T-cell count increase than initiating treatment with AZT. This strategy could be considered in patients with baseline anaemia or low CD4(+) T-cell count. If confirmed in a larger study, this may guide global recommendations on antiretroviral initiation where AZT is more commonly used than TDF.