Singapore lags in latent tuberculosis screening among HIV-positive individuals

Latent tuberculosis (TB) infection (LTBI) screening in Singapore, a nation with intermediate TB burden, appears to be below average among individuals who are HIV-positive, a study has revealed.

“Our cohort consisted of clinically advanced HIV disease as 76 percent had CD4 ≤200 cells/mm³ at active TB disease diagnosis. However, only 0.6 percent (n=2) of patients in this study had LTBI screened on HIV diagnosis, which is low,” according to a team of researchers from National University Hospital (NUH) in Singapore.

This is consistent with inadequate LTBI screening reported in developed countries with low TB and HIV burden, the team added. The LTBI screening rates among HIV-infected patients were 35 percent in the UK, 32 percent in the US, 55 percent in New Zealand, and 65 percent in Italy. One study further noted that LTBI tests were more frequently performed on foreign-born patients, older individuals, and those with low CD4 cell count. [J AIDS HIV Res 2015;7:109-116; Thorax 2017;72:180-182; AIDS Care 2017;29:1504-1509; Int J Infect Dis 2020;92:62-68]

“People living with HIV are more susceptible to active TB disease as HIV infection increases the risks of developing TB by 16 to 27 times compared to those without HIV. TB remains a leading cause of death in the HIV population worldwide even though TB is both preventable and treatable,” the researchers said.

As such, the World Health Organization (WHO) promotes preventive action of TB at the time of HIV diagnosis, with LTBI treatment expected to lower TB-related morbidity and mortality among HIV-infected patients. Indeed, TB preventive therapy has been shown to reduce the risk of active TB disease by 32 percent in those with HIV and considered a key component to halve TB transmission in patients living with HIV. [Cochrane Database Syst Rev 2010;2010:CD000171]

HIV and active TB

The present cohort included 4,015 HIV-infected patients managed at NUH and the National Centre for Infectious Diseases (NCID) over 11 years. A total of 320 patients were diagnosed with active TB disease (mean CD4 count at diagnosis 125.0 cells/mm³), of whom 93.8 percent had microbiologically proven TB, 89.1 percent were men, 45 percent were smokers, and 12.5 percent had diabetes mellitus.

HIV diagnosis was established ≥6 weeks before active TB disease diagnosis in 130 (41 percent) patients, ≥6 weeks after TB in seven (2 percent), and concomitantly with TB (within 6 weeks of each other) in 176 (55 percent). Time to TB diagnosis relative to HIV diagnosis was unknown in the remaining seven patients (2 percent). [Int J Infect Dis 2021;doi:10.1016/j.ijid.2021.09.048]

Compared with the group of patients with HIV and active TB concomitantly diagnosed or who had first received a TB diagnosis, the group of those with HIV diagnosed first was more likely to have higher CD4 counts (≥200 cells/mm³; p=0.003), be already on antiretroviral therapy (ART; p<0.001), and to have trace Acid Fast Bacilli (AFB) smear (p=0.046). Interestingly, there were no between-group differences noted in the proportion of patients with an abnormal or normal chest X-ray (CXR) score, immune reconstitution inflammatory syndrome (IRIS), or TB-related deaths.

Explaining the findings above, the researchers pointed out that active TB disease remains a common infection, despite receiving ART and having a higher CD4 count. They also stressed that caution be exercised when using CXR to screen for active TB disease in HIV-infected patients.

“A high index of suspicion, especially in patients presenting with prolonged cough, is required for timely diagnosis of TB in HIV positive patients for prompt isolation and initiation of TB treatment,” they said.

Additionally, the researchers found a delay in the initiation of ART treatment, particularly for those with CD4 ≤50 cells/mm. While WHO recommends initiation of ART for HIV-TB coinfected patients within the first 2 months of starting TB treatment and within 2 weeks of active TB diagnosis in those severely immunocompromised patients with low CD4, ART was started within 2 weeks in only 14 percent of patients with CD4 ≤50 cells/mm³ in the present study. Additionally, a significant number of patients (51.7 percent) initiated ART more than 2 months following active TB diagnosis.

Taken together, the data indicate that “there remains a good window of opportunity to reduce the prevalence of HIV-TB coinfection, together with prompt initiation of ART to improve treatment outcomes in this population,” according to the researchers. “Further improvements are needed to target TB infection care in HIV patients as recommended by the WHO.”