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Run-up to programmatic management of latent tuberculosis infection in HIV-infected people in Lithuania

The project results have been published in PLoS ONE: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0282046  

Grantee

Vilnius University, Vilnius, Lithuania

Project status: Completed

Main applicant and principal investigator

Prof. Raimonda Matulionyte, Vilnius University

Deputy applicant

Elzbieta Matulyte, PhD student, Vilnius University

Collaborators 

  1. Zavinta Kancauskiene, University Hospital of Klaipeda, Lithuania
  2. Aidas Kausas, Republican Siauliai County Hospital, Lithuania

Background

Tuberculosis (TB) continues to be a public health problem in Lithuania and is the leading cause of death among people living with HIV (PLHIV). It is the most common AIDS-indicative disease (>50% in 2018), more common than in any other EU/EEA country. The prevention of active TB disease by treatment of latent TB infection (LTBI) is a critical component of the WHO End TB Strategy. However, until June 2018 PLHIV were not screened for LTBI in Lithuania. Therefore LTBI prevalence is unknown both among PLHIV and the general population and no special actions have been taken to prevent active disease at a population level.

Objective

The study objective was to evaluate the background situation of active and latent TB infection in PLHIV in Lithuania and to determine the optimal diagnostic tools for successful implementation of programmatic management of LTBI in PLHIV in Lithuania.

The specific study aims were:

Methods

The dynamics of morbidity and outcome-related risk factors for active TB among persons diagnosed with HIV during 2008-2020 was evaluated through a retrospective chart review using the database of the State Tuberculosis Information System. LTBI prevalence was assessed by recruiting and testing 200 HIV-positive and 400 HIV-negative patients using Interferon Gamma Release Assay (IGRA) tests followed by tuberculin skin tests (TST); the diagnostic values of each LTBI testing approach were measured; while LTBI risk factors were evaluated through a structured questionnaire administered to both study groups. PLHIV with a positive TST and/or IGRA result were further screened for active TB (clinical symptoms, chest X-ray and sputum culture) and the sensitivity, specificity, positive and negative predictive values of the clinical and radiological investigations for diagnosing active TB were measured.

Results

From the retrospective assessment, among 3431 people living with diagnosed HIV, 311 patients (9,1%) were registered with active TB over the period 2008 to 2020. The rate of drug-susceptible TB was 55%; treatment was unsuccessful in 39% of cases and imprisonment was associated with unsuccessful treatment outcome. The rate of drug-resistant TB was 45%; in this group, treatment was unsuccessful in 65% of cases and female gender and MDR-TB were associated with higher risk of unsuccessful treatment. Sixty-seven percent knew their HIV-positive status before TB diagnosis, the median time to TB diagnosis was 7 years; 80% were unemployed, 51% had a history of drug injection, 36% abused alcohol and 64% had a history of imprisonment.

For the prospective part of the study, 200 HIV-positive and 400 HIV-negative patients were recruited. The prevalence of LTBI (measured by a positive IGRA test) was found to be significantly higher among PLHIV compared to the HIV-negative control group (proxy for the general population): 19.0% versus 11.5% (p=0,01). The TST positivity rate in PLHIV was 7.8% and was lower than the 11.5% measured for HIV-negative comparison group (p=0.04). TST appeared ineffective for diagnosis of LTBI in Lithuanian PLHIV due to compromised sensitivity in immunocompromised patients and limited specificity in immunocompetent patients with prior BCG vaccination. The feasibility of TST screening was also limited by operational disadvantages (tuberculin storage requirements and a need for patient recall). Injecting drug use was associated with LTBI in PLHIV. In HIV-uninfected individuals, LTBI was associated with a history of contact with a TB patient.

A number of training sessions supporting capacity-building and enhancing patient-centered care strategies for nurses and physicians were arranged in all participating infectious diseases and pneumology clinics.

Conclusions / impact

The study showed that injecting drug use, alcohol abuse, unemployment and imprisonment were very common in the HIV-TB co-infected population in Lithuania. These findings emphasize the need of screening for active TB during and after incarceration, including testing for LTBI and LTBI treatment if applicable. Integrated services of HIV/TB and substance abuse treatment among HIV-TB co-infected patients should be considered.

LTBI prevalence among PLHIV in Lithuania is high compared to a European average estimate of 12.2% (9.8-14.5%) [1]. The significant association with injecting drug use suggests that IDU is a common driver of the HIV-TB epidemics and emphasizes the need to enhance integrated HIV, TB (and HCV) and substance abuse treatment services in this vulnerable population group, seeking to provide person-centered rather than disease-centered care.

In conclusion, the project identified country-specific circumstances that should be considered for the implementation of programmatic management of LTBI in PLHIV in Lithuania. IGRA testing is recommended above TST when testing Lithuanian PLHIV for LTBI. The study also helped reduce barriers to testing for LTBI in PLHIV, assessed the effectiveness, feasibility and acceptability of the LTBI screening programme in PLHIV, raised awareness about LTBI among patients and health care providers and facilitated collaboration with other geographically distinct clinics providing care for PLHIV in Lithuania with the ultimate aim of disseminating knowledge and improving equity in quality of care across the country.

More information

The project results have been published in PLoS ONE and the full paper can be retrieved here: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0282046  

The study findings have also been disseminated through presentations and abstracts at various national and international conferences and meetings: