Latent and subclinical tuberculosis in HIV infected patients: a cross-sectional study

Abstract

BackgroundHIV and tuberculosis (TB) are commonly associated. Identifying latent and asymptomatic tuberculosis infection in HIV-positive patients is important in preventing death and morbidity associated with active TB.MethodsCross-sectional study of one time use of an interferon-gamma release assay (T-SPOT.TB - immunospot) to detect tuberculosis infection in patients in a UK inner city HIV clinic with a large sub-Saharan population.Results542 patient samples from 520 patients who disclosed their symptoms of TB were tested. Median follow-up was 35 months (range 27-69). More than half (55%) originated from countries with medium or high tuberculosis burden and 57% were women. Antiretroviral therapy was used by 67%; median CD4 count at test was 458 cells/μl. A negative test was found in 452 samples and an indeterminate results in 40 (7.4%) but neither were associated with a low CD4 count. A positive test was found in 10% (50/502) individuals. All patients with positive tests were referred to the TB specialist, 47 (94%) had a chest radiograph and 46 (92%) attended the TB clinic. Two had culture-positive TB and a third individual with features of active TB was treated. 40 started and 38 completed preventive treatment. One patient who completed preventive treatment with isoniazid monotherapy subsequently developed isoniazid-resistant pulmonary tuberculosis. No patient with a negative test has developed TB.ConclusionsWe found an overall prevalence of latent TB infection of 10% through screening for TB in those with HIV infection and without symptoms, and a further 1% with active disease, a yield greater than typically found in contact tracing. Acceptability of preventive treatment was high with 85% of those with latent TB infection eventually completing their TB chemotherapy regimens. IGRA-based TB screening among HIV-infected individuals was feasible in the clinical setting and assisted with appropriate management (including preventive treatment and therapy for active disease). Follow-up of TB incidence in this group is needed to assess the long-term effects of preventive treatment.

Decreasing cost effectiveness of testing for latent TB in HIV in a low TB incidence area

“…In part, this was due to physicians' poor adherence to the recommendation [22]. In those that were given preventive treatment, however, there were no subsequent cases of active TB, a finding that has been mirrored in more recent studies from Western Europe [18,30]. Our assumptions of uptake and LTBI treatment completion are based on contemporary studies from London [18]; however, by using results from a meta-analysis on TST-positive HIV-infected individuals, comparing LTBI treatment against placebo, we may have underestimated the efficacy of LTBI treatment in people with a positive IGRA (as modelled here) and hence the cost-effectiveness of testing [3,18].…”

“…We varied the uptake of testing, sensitivity of IGRA, uptake and effectiveness of isoniazid preventive therapy using published data. The effectiveness varied between 40% (an estimate of protection given non-optimal adherence) and 100% (a figure approached in studies in high-resource, low TB incidence areas) [18,22]. The impact on quality of life was varied for LTBI preventive treatment and active TB treatment.…”

“…We assumed the following: all HIV-positive patients would be eligible except those excluded because of a diagnosis of active TB before or within 3 months of HIV diagnosis; initial testing would occur in 87% of those eligible [18]; subjects were tested on one occasion, but 3% would have indeterminate IGRA results, leading to one repeat test [19]; TST/IGRA positivity rates were estimated to be 13% in subjects originating from a country in sub-Saharan Africa, 10% from middle TB incidence countries and 3% from low TB incidence countries [18]; sensitivity of an IGRA was 91% [20]; uptake of latent TB preventive treatment was 87% with 62% effectiveness using six months of isoniazid [3,18]; and QALY reductions for active and latent TB were −0.676 and −0.007 respectively, using previously published estimates for this age group with active TB disease (see section A in the online supplementary material) [11].…”

Tuberculosis infection and disease in people living with HIV in countries with low tuberculosis incidence

“…13,15,17,19,23,25,31,32,37,43,44,46,49,52,53 Similarly, PLHIV who were born in, or long-term residents of, countries with high TB incidence had higher rates of LTBI and active TB. [10][11][12][13]17,18,[22][23][24]26,45,56 Few studies examined the effects of country of birth and ethnicity independently of each other; those that did found no independent associations between ethnicity and country of birth and active TB 34,46 or LTBI. 14,17 However, a more recently published study stratified the risk of developing active TB by ethnicity and the TB incidence in country of birth and demonstrated that ethnicity and the incidence of TB in the patient's country of birth independently increase the risk of developing TB for PLHIV.…”

QFT-IT for diagnosing and screening TB infection in HIV patients: CD4 cells count as an important influential factor

“…As far as the patients with indeterminate results were concerned, the median CD4 cell count was always less than 200 cells/ml, which was similar to previous reports. [1][2][3] In conclusion, the QFT-IT could be a potential, simple and feasible method for diagnosing and screening TB in HIV-infected patients. The patients' CD4 cells count is an important influential factor when interpreting the results of QFT-IT.…”