QUANTIFERON-GOLD PLUS STUDY REVEALS LIMITATIONS IN TUBERCULOSIS SCREENING AMONG PEOPLE LIVING WITH HIV IN HIGH-TRANSMISSION AREAS

The study was recently published in the Journal of Infectious Diseases by Oxford Academic, with CISM researcher Dinis Ngwenha as one of the lead authors.

Tuberculosis remains one of the major public health challenges in Mozambique, which ranks among the countries with the highest burden of the disease and TB/HIV co-infection globally. The country reports a high number of cases annually, with a significant impact on vulnerable populations, particularly people living with HIV (PLHIV). Persistent community transmission remains one of the main challenges for disease control.

Currently, tuberculosis control strategies include early diagnosis, appropriate treatment of active cases, and the implementation of preventive treatment among high-risk groups such as PLHIV. Common regimens include 3HP (rifapentine and isoniazid for three months), p3HP (annual repeated regimen), and 6H (daily isoniazid for six months), aiming to reduce the progression from latent infection to active disease.

A multicentre study conducted in Mozambique, South Africa, and Ethiopia assessed the evolution of QuantiFERON-Gold Plus (QFT-Plus) test results among PLHIV undergoing different tuberculosis preventive treatment (TPT) regimens, highlighting important challenges in interpreting this test in high-transmission settings. In Mozambique, the study was implemented by the Manhiça Health Research Centre (CISM) between 2017 and 2019, under the WHIP3HP project, which recruited 4,014 participants, including 599 in the country. The study was funded by the Stop TB Partnership and Sanofi-Aventis Groupe.

QuantiFERON-Gold Plus (QFT-Plus) is a laboratory test that evaluates the immune response to the bacteria causing tuberculosis and is commonly used to detect latent infection. Compared to the traditional tuberculin skin test, it offers higher specificity in several clinical settings.

19% of participants showed reversion of results

In the study, which followed more than 1,500 participants over two years, approximately 13% of individuals who initially tested negative converted to positive results within the first year, with no significant differences between the TPT regimens evaluated (3HP and 6H). Between 12 and 24 months, conversions continued to occur, although at a lower proportion. Additionally, about 19% of participants showed reversion of results, changing from positive to negative, with no significant variation across treatment groups. It was also observed that individuals with a positive result at baseline had a higher risk of developing tuberculosis during follow-up.

The findings demonstrated considerable variability in QFT-Plus results, even among individuals receiving preventive treatment, with frequent conversions and reversions. These results suggest that in high-transmission settings such as Mozambique, continuous exposure to the bacteria may significantly influence test outcomes, complicating their interpretation over time.

According to CISM tuberculosis researcher Dinis Nguenha, “this study is particularly relevant because it challenges the expectation that preventive treatment clearly reduces detectable new infections. In high-transmission settings, individuals remain exposed, which limits the observable impact on immunological tests.” Meanwhile, one of the lead authors, Belén Saavedra, adds that “the frequent fluctuations in QFT-Plus results indicate that the test may not be sufficiently stable to monitor preventive treatment in people living with HIV, highlighting the need to identify more robust biomarkers.”

Despite these limitations, the authors conclude that QFT-Plus retains prognostic value, as individuals with a positive baseline result have a higher risk of developing tuberculosis. However, the findings reinforce the need to rethink screening and follow-up strategies in high TB/HIV burden countries such as Mozambique.

Reference:

• Saavedra-Cervera B, Nguenha D, Chihota V, Yimer G, Fernández-Escobar C, Mngadi K, Brumskine W, Martinson N, Wang SH, Masilela L, Waggie Z, Martínez L, van den Hof S, Charalambous S, Cobelens F, Chaisson R, Grant AD, Fielding K, Churchyard G, Garcia-Basteiro AL. Dynamics of Quantiferon-Gold Plus results in a large TB preventive treatment trial across three high-burden HIV/TB countries. J Infect Dis. 2026 Mar 17:jiag165. doi: 10.1093/infdis/jiag165. Epub ahead of print. PMID: 41843759.