What are the diagnostic options available for latent TB infection?

Previously, the only tool available for identifying LTBI was the tuberculin skin test (TST), or Mantoux test. The TST is an in vivo test that measures immune responses to tuberculin purified protein derivative (PPD), which is made up of a multitude of bacterial proteins. Most of these proteins are present in the BCG vaccine, and shared with many environmental mycobacteria. As such, immunological reactions to the PPD reagent used in the TST may be nonspecific and may contribute to increased rates of false-positive results (8). IGRAs offer a new paradigm in diagnosing TB infection. QFT is the most clinically tested and proven IGRA, with over 1000 peer-reviewed, published clinical papers.

What are the limitations of the TST in individuals with HIV?

A variety of factors, other than TB infection, are known to induce a false-positive TST result. These include BCG vaccination, exposure to NTM, the inherent boosting effects of prior TST testing, and subjectivity and variability (intraobserver and inter-observer) when reading test results (8–9). Decreased specificity has been shown to occur in those who have been BCG vaccinated. False-positive results often lead to unnecessary treatment for TB infection with possible detrimental side effects (10). False-negative results are also a common limitation of the TST (11). The TST is unable to distinguish between anergic reactions and negative results. Following the initial intradermal injection of PPD, recipients are required to return within 72 hours to permit reading of the result. Failure to return for TST reading, often in the range of 30-50% of those tested, is common in HIV-infected populations, thereby undermining the sensitivity of TST and increasing the costs of screening (12–14).

What is the correlation between QFT and M. tuberculosis exposure in HIV-positive individuals?

HIV-positive individuals are at risk of progressing to active TB disease and outbreaks, due to the combination of immune suppression from HIV and population risks such as homelessness, incarceration and drug use (15).

What is the impact of QFT test performance on the CD4+ T cell count?

A large number of studies have analyzed QFT performance in individuals living with HIV. Some studies have shown that the sensitivity of QFT in HIV co-infected individuals is impaired compared with HIV-negative patients with TB disease, although to a lesser degree than the TST (3).

A significant benefit of QFT over the TST is that it incorporates a positive control (15). However, like the TST, QFT relies on functional CD4+ cells, and its performance can be negatively influenced by low and impaired CD4+ cell counts in HIV-infected individuals (16). Unlike the TST, the positive control of QFT provides an indicator of the overall immune function. An indeterminate QFT result in an HIV-infected person with a low CD4+ cell count can provide valuable information. It suggests possible anergy and does not necessarily indicate a failed test (17, 18) (Table 1).

* All indeterminate results were due to a failure to respond adequately to the positive control.

Do I need to investigate active TB based upon a positive QFT test?

A positive QFT result indicates the person tested is likely infected with M. tuberculosis. The individual with a positive QFT result should have a medical evaluation that includes a symptom review, risk factor assessment, chest x-ray and physical examination to determine the diagnosis of active TB or LTBI.

What does the literature say about QFT use in the HIV population?

Numerous studies have investigated the use of QFT in HIVpositive populations. The characteristics of these studies are outlined in the QFT HIV Clinical Guide, which can be downloaded below. Of note is that QFT has been shown to have equal or higher sensitivity when compared with the TST. Perhaps the biggest disadvantage of the TST is that it lacks an internal control to distinguish false negative results due to anergy from true negative results.