Key points The tuberculosis (TB) burden in the Asia Pacific is high. People living with HIV are at high risk of TB disease despite the immune restoration brought on by antiretroviral therapy. Latent TB infection screening with either tuberculin skin test or interferon-gamma release assay for newly diagnosed HIV patients is an effective strategy for minimizing the TB burden.

Opportunistic infection is the hallmark of the immunocompromised state associated with HIV infection. In the last decade, advances in antiretroviral therapy (ART) and its early initiation have led to effective immune restoration in people living with HIV (PLHIV), as demonstrated by the significant reduction of severe systemic infections caused by opportunistic pathogens. Among the range of opportunistic infections causing threats to PLHIV, however, tuberculosis (TB) is unique in its occurrence even in relatively immunocompetent hosts. In 2020, there were an estimated 10 million new TB cases globally of whom over 8% were HIV infected.1 Notably, the Asia Pacific region has one of the highest burdens of TB in the world. Despite increased uptake of ART, the burden of TB-associated morbidity and mortality in PLHIV has remained high.

To minimize HIV-associated TB burden, early diagnosis and symptomatic screening are necessary but insufficient strategies. Detection of latent TB infection (LTBI) followed by short-term antimycobacterial preventive therapy constitutes an add-on approach to reducing TB reactivation diseases. In practice, the diagnosis of LTBI can be made either by performing tuberculin skin test (TST) or an interferon-gamma release assay (IGRA). The potential influence of previous Bacille Calmette-Guerin (BCG) immunization, observer dependency and the need for consecutive clinic visits are the drawbacks of TST, while the high cost and requirement of laboratory support are hindrances in using IGRA for LTBI testing. Poor comparability of results between tests has added to the complexity when considering the development of practicable LTBI strategy for PLHIV. There is the need for the development of a simple, affordable, reliable test for supporting the implementation of LTBI screening, especially in low-to-middle-income country (LMIC) settings.

In the Asia Pacific where many LMICs are present, it is not surprising that the implementation of LTBI screening in PLHIV is highly variable, as reported by an expert panel in 2018.2 The situation is not unlike that in Western countries as reported in an evaluation study from the United Kingdom.3 Apart from the lack of a standard test, the heterogeneity of LTBI screening has also arisen from discrepancies between guidelines that fail to inform unified best practice. With the accumulated scientific literature and diverse guidance, the adoption of country- or clinic-level strategies is often subject to the varied interpretation of the respective local authority.4 The recent World Health Organization (WHO) recommendation of providing LTBI treatment to all PLHIV regardless of screening in endemic countries5 may mean a standard practice in selected jurisdictions, while clinics in other cities/countries would be considering this as yet another option. In the WHO's latest TB report, the global number of PLHIV on LTBI treatment has reached 7.2 million, which is above the 6 million target set for 2018–2022.1 It must be cautioned however that there is a wide geographic variation in the uptake of LTBI treatment strategy. In 2020, some 39% of PLHIV newly enrolled in care were on LTBI treatment in the two WHO Asian Regions compared to that of 71% in the African Region. It would be important to monitor the situation with a cascade approach to track firstly the proportion of PLHIV in care who have been screened, secondly the proportion started on LTBI treatment and thirdly the proportion who have completed treatment, both for newly diagnosed PLHIV and those in care.

Rather than the design of a one-size-fit-all LTBI control strategy, it would be more practicable to advocate for a minimum standard to ensure broad coverage in the community. In non-endemic countries and places that have not adopted universal LTBI treatment, screening is the key strategy for enabling PLHIV to be offered risk-based preventive treatment. The best timing for considering a diagnosis of LTBI is unarguably when one is diagnosed with HIV infection. While LTBI treatment without screening has its merits, the concurrent prescription of LTBI treatment and ART poses challenge. Clinical assessment to exclude active TB diseases and the concern for drug–drug interaction, alongside the need for considering other co-infections such as sexually transmitted infections, hepatitis B and hepatitis C, would overwhelm the agenda for the initial consultation(s). Mindful that TST is not a perfect tool, its performance at the first visit followed by an assessment 48–72 h later can prepare patients psychologically for the preventive therapy in accordance with the assessed risk. A positive TST result in an immunocompromised patient is by itself a strong indication for LTBI treatment, even if one has previously been vaccinated with BCG. The testing with IGRA, or IGRA + TST, could be alternative approach, whereas TST can be a minimum standard. A positive test at baseline was significantly associated with TB disease development,6 implying that screening at HIV diagnosis should be prioritized, while subsequent periodic testing may not be essential. For LTBI treatment, a 6- to 12-month course of isoniazid or rifamycin-containing regimen has been proven efficacious and safe for preventing TB diseases and death.7

Whereas LTBI treatment contributes to the reduction of reactivation diseases, prompt and continued ART enables the immune system to recover, thereby minimizing future risk of TB reactivation. This latter strategy for reducing TB burden works only if ART is offered as early as possible. The ‘treatment-as-prevention’ principle of ART applies both to HIV infection as well as TB reactivation. Provided that late presentation is kept to a minimum, prompt initiation of ART in the same setting as LTBI screening as soon as possible after diagnosis form the best dual strategy for reducing population burden of HIV and TB co-infection. The challenge rests with the promotion of HIV testing in people at risk of HIV and the prompt introduction of LTBI screening for all newly diagnosed HIV patients.

The author's TB research is supported by General Research Fund (grant number: 14104918) from Research Grants Council of Hong Kong, China.