RESUMO
Background: QuantiFERON-TB-Gold-in-tube (QFT-GIT) is an interferon-gamma release assay (IGRA) used to diagnose latent tuberculosis infection. Limited data exists on performance of QuantiFERON-TB Gold-Plus (QFT-Plus), a next generation of IGRA that includes an additional antigen tube 2 (TB2) while excluding TB7.7 from antigen tube 1 (TB1), to measure TB specific CD4+ and CD8+ T lymphocytes responses. We compared agreement between QFT-Plus and QFT-GIT among highly TB exposed goldminers in South Africa. Methods: We enrolled HIV-negative goldminers in South Africa, aged ≥33 years with no prior history of TB disease or evidence of silicosis. Blood samples were collected for QFT-GIT and QFT-Plus. QFT-GIT was considered positive if TB1 tested positive; while QFT-Plus was positive if both or either TB1 or TB2 tested positive, as per manufacturer's recommendations. We compared the agreement between QFT-Plus and QFT-GIT using Cohen's Kappa. To assess the specific contribution of CD8+ T-cells, we used TB2-TB1 differential values as an indirect estimate. A cut-off value was set at 0.6. Logistic regression was used to identify factors associated with having TB2-TB1>0.6 difference on QFT-Plus. Results: Of 349 enrolled participants, 304 had QFT-Plus and QFT-GIT results: 205 (68%) were positive on both assays; 83 (27%) were negative on both assays while 16 (5%) had discordant results. Overall, there was 94.7% (288/304) agreement between QFT-Plus and QFT-GIT (Kappa = 0.87). 214 had positive QFT-Plus result, of whom 202 [94.4%, median interquartile range (IQR): 3.06 (1.31, 7.00)] were positive on TB1 and 205 [95.8%, median (IQR): 3.25 (1.53, 8.02)] were positive on TB2. A TB2-TB1>0.6 difference was observed in 16.4% (35/214), with some evidence of a difference by BMI; 14.9% (7/47), 9.8% (9/92) and 25.3% (19/75) for BMI of 18.5-24.9, 18.5-25 and >30 kg/m 2, respectively (P=0.03). Conclusion: In a population of HIV-negative goldminers, QFT-Plus showed high agreement with QFT-GIT, suggesting similar performance.
RESUMO
BACKGROUND: Early and accurate detection of HIV is crucial when using pre-exposure prophylaxis (PrEP) for HIV prevention to avoid PrEP initiation in acutely infected individuals and to minimize the risk of drug resistance in individuals with breakthrough infection. OBJECTIVE: To determine if fourth-generation antigen/antibody (Ag/Ab) rapid diagnostic tests (RDT) would have detected HIV infection earlier than the third-generation RDT used in MTN-003 (VOICE). STUDY DESIGN: 5029 VOICE participants were evaluated with third-generation Alere Determine™ HIV-1/2, OraQuick ADVANCE® Rapid HIV-1/2, Uni-Gold™ Recombigen® HIV-1/2 and Bio-Rad GS HIV-1/2+O EIA; and fourth-generation Alere Determine™ HIV-1/2 Ag/Ab Combo, Conformité Européene (CE)-Marked Alere™ HIV Combo and Bio-Rad HIV Combo Ag/Ab EIA. Multispot®, GS HIV-1 Western Blot (WB) and Geenius™ (Bio-Rad) were also evaluated. RESULTS: Of 57 antibody-negative pre-seroconversion plasma samples with HIV RNA >20 copies/mL identified, 16 (28%) were reactive by CE-Marked Alere™ HIV Combo (1 Ab; 9 Ag; 6 Ag/Ab reactive) and 4 (7%) by Alere Determine™ HIV-1/2 Ag/Ab Combo (2 Ab; 2 Ag; 0 Ag/Ab reactive) (p=0.0005). Multispot® confirmed only 1 of 16 acute infections while WB and Geenius™ confirmed none. GS HIV Combo Ag/Ab EIA identified 27 of 57 (47%) pre-seroconversion RNA-positive samples. CONCLUSION: In VOICE, 28% of infections missed by current third-generation RDT would have been identified with the use of CE-Marked Alere™ HIV Combo. Geenius™, Multispot® and WB were all insensitive (<10%) in confirming infections detected by fourth-generation assays. An improved diagnostic algorithm that includes a fourth-generation RDT with HIV RNA testing will be essential for efficiently identifying seroconverters on PrEP.