S Capocci

Health status and quality of life in tuberculosis

Tuberculosis (TB) is a leading cause of global morbidity, yet there is limited information regarding its impact on quality of life and health status. This is surprising given the implications for patient care, the evaluation of novel treatments or preventative strategies, and also health policy. Furthermore, there is no validated TB-specific instrument that measures health status, and thus a wide and non-standardized range of assessment tools have been employed. The studies to date have chosen a number of different comparator populations, and in many TB endemic areas there is a lack of normative data regarding the health status of the general population. Systematic evaluations of quality of life are urgently needed in specific groups, including those with extrapulmonary TB, drug-resistant disease, HIV co-infection, and latent TB infection, and in children with TB; the assessment of post-treatment disability is also required.

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

Testing for latent tuberculosis infection (LTBI) in HIV-infected persons in low tuberculosis (TB) incidence areas is often recommended. Using contemporary, clinical data, we report the yield and cost-effectiveness of testing all HIV attendees, two current UK strategies and no LTBI testing. Economic modelling was performed utilising 10-year follow up data from a large HIV clinical cohort. Outcomes were numbers of cases of active TB and incremental cost per quality-adjusted life year (QALY) gained. Between 2000 and 2010, 256 people were treated for TB/HIV co-infection. 72 (28%) occurred ≥3 months after HIV diagnosis and may have been prevented by LTBI testing. Between 2000 and 2005, the incremental cost per QALY gained for the British HIV Association (BHIVA) and UK National Institute of Care Excellence (NICE) strategies, and testing all clinic attendees was €6270, €6998 and €33 473, respectively. These rose to €9332, €32 564 and €74 067, respectively, between 2005 and 2010. Probabilistic sensitivity analysis suggested that at a threshold of €24 000 per additional QALY, the most cost-effective strategies would be NICE or testing all in 2000–2005 and BHIVA during 2005–2010. Both UK testing regimens missed cases but are cost-effective compared with no testing. Using recent data, they all became more expensive, suggesting that alternative or more targeted TB testing strategies must be considered. Targeted latent TB testing strategies in HIV are cost effective, but lately have become more expensive http://ow.ly/JnWjU

Frequency and significance of indeterminate and borderline Quantiferon Gold TB IGRA Results

The Quantiferon Gold test is one of two commercially available tuberculosis (TB) interferon-γ release assays (IGRAs) recommended for the diagnosis of latent TB infection [1]. A Quantiferon Gold test is considered positive if the result is ≥0.35 IU·mL−1 [2]. However, longitudinal studies have shown that a significant number of test reversions and conversions occur if results just above or below this threshold are repeated [3, 4]. This variation may be due to random chance or other factors such as test-related errors, differences in absolute lymphocyte numbers and within-subject variability of the interferon-γ response [5, 6]. The high proportion of conversions and reversions around the 0.35 IU·mL−1 cut-off has led some to suggest that a borderline or equivocal range should be used [7], as this avoids treatment of individuals who do not have a ‘stable’ positive result, as well as failure to treat those just below the 0.35 threshold who would convert to a positive result if the test were repeated [6]. Borderline and equivocal results for the Quantiferon Gold test are common and repeated borderline tests often change http://ow.ly/PDDZ30fqJ1c

Influenza immunisation: knowledge and actions taken by UK HIV-positive adults

Influenza is an important cause of respiratory illness in the general population and is responsible for exacerbations of pre-existing respiratory disease (which are more common in people living with HIV) [1,2]. Current evidence suggests that individuals with HIV who are not using antiretroviral therapy (ART) have a higher rate of complications associated with influenza and an increased duration and severity of illness – although the extent to which ART reduces this is uncertain [3,4]. The Trivalent Inactivated Influenza Vaccine (TIV) appears effective in preventing influenza in individuals with HIV [5]. It is recommended for all HIV-positive patients in the UK with a target of 95% coverage [6] although uptake may be suboptimal [7–15]. There are limited data regarding rates of immunisation in the UK HIV-positive population, or the health beliefs concerning influenza immunisation which may influence its uptake. Here we report data from a large metropolitan HIV service regarding the use and health beliefs surrounding influenza immunisation in people living with HIV infection. We conducted a cross-sectional study of HIV-positive adults presenting for routine care at a large urban HIV care service in London, UK, between September and December 2014. Individuals attending clinic appointments within the ambulatory care service during the study period were invited to complete an anonymous questionnaire detailing demographics, ART use, influenza immunisation in the previous year and intentions regarding immunisation in the 2014–2015 season. For those who had not been vaccinated, the reasons underlying this decision were sought. Questions explored each participant’s knowledge regarding the efficacy of the influenza vaccine and the clinical course of influenza in HIV-infected individuals. Two hundred and fifty-three individuals completed the questionnaire between October and December 2014: 195 participants were male (83% of those reporting their gender), 39 female and 19 did not state their gender; 177 (70%) were White, 47 (18.6%) Black African or Black Caribbean and 89% were using ART. The median age of study participants was in the 55–64 age category compared to a median age in the total clinic population of 47 years (interquartile range, 41–53 years). One hundred and sixty-three respondents [64%; 95% confidence interval (CI) 58–70%] had or planned to have an influenza immunisation in 2014–2015 and 171 participants (68%; CI 61–73%) recalled immunisation in 2013– 2014. Of these, 68 (40%) reported that immunisation was given in GP practices and 56 (33%) in HIV care services, with the remainder provided by pharmacies, supermarkets and workplaces. Immunisation rates were lower in younger patients, with 157 of 223 (70%) above the age of 45 years reporting immunisation in the 2013–2014 season compared to 14 of 30 (47%) younger participants (P = 0.018, vtest). Immunisation rates were greater in women: 34 of 39 women (87%) reported immunisation compared to 65% of men (127 of 195, P = 0.025). There was no significant difference between White and NonWhite ethnic groups. The use of ART was associated with a higher rate of immunisation uptake (70% vs. 43% P = 0.01), although only 21 participants were not using ART. Amongst 65 participants stating that they had not been immunised in 2013–2014, reasons given were as follows: 16 (25%) did not think that they needed immunisation, 15 (23%) reported concern about adverse events and 14 Correspondence: Marc Lipman, Centre for Respiratory Medicine, Royal Free London NHS Foundation Trust, Pond Street, London NW3 2QG, UK. Tel: + 44 207 317 7560; fax: +44 207 317 7561; e-mail: marclipman@nhs.net

Expanded blood borne virus testing in a tuberculosis clinic. A cost and yield analysis

OBJECTIVES Testing for HIV is a standard of care for people with active tuberculosis (TB). People investigated for TB in the UK often originate from areas with a high prevalence of HIV and other blood borne viruses (BBV). However, assessment for these infections is patchy. We determined the yield and costs of different testing strategies for BBV in a UK TB clinic. METHODS Since 2009, it has been routine to test all TB clinic attendees. Demographic, clinical and virological data were retrospectively extracted from patient notes and hospital databases. RESULTS Over 3 years, 1036 people were assessed in the TB service. 410 had a final diagnosis of active TB. HIV testing of the latter population diagnosed 27 new HIV cases at a cost of £3017. When BBV testing was offered to all clinic attendees, a further 6 (total 33) new HIV, 5 Hepatitis B (HBV) and 2 Hepatitis C (HCV) diagnoses were made at a total cost of £22,170. CONCLUSIONS We have identified previously undiagnosed HIV, HBV and HCV in a TB clinic population. Our data suggest that despite increasing upfront expense, the associated yield argues strongly for BBV testing to be offered to all patients being investigated for possible TB, irrespective of their final diagnosis.

S88 Neither uk tuberculosis infection testing guideline appears cost-effective in a contemporary hiv infected population

UK guidelines advise testing for latent tuberculosis infection (LTBI) in people with known HIV. Both National Institute for Health and Care Excellence (NICE) 2011 and 2016, and British HIV Association (BHIVA) guidelines use targeted testing, in comparison to those from other countries, notably the United States. None of these have been compared for cost-effectiveness in a contemporary HIV population. We sought to determine the cost-effectiveness of each UK guideline from an NHS perspective, plus alternatives, using prospective data. All patients with a new HIV diagnosis attending an ambulatory HIV clinic, plus a sample of those with known HIV were approached; and offered a symptom questionnaire, chest radiograph (CXR), tuberculin skin test (TST), blood interferon gamma release assay (IGRA) and induced sputum for mycobacterial culture (IS). The uptake and results were used to calculate the cost-effectiveness of thirty different testing strategies using univariate, multivariate and probabilistic sensitivity analyses (PSA). 219 subjects, representative of the total clinic population, took part. 73% were male, 28% black African and 95% on antiretroviral therapy (ART). During testing, 2 cases (0.9%) of subclinical TB and 14 (6%) of LTBI were detected. Half the patients with LTBI completed preventive treatment. Over a median of 28 months follow up, no new cases of active TB were identified. When compared to no testing, only three of the thirty strategies were below the maximum NICE threshold for cost-effectiveness <£30,000/QALY gained. Testing black Africans with just TST or IGRA cost £23,429/QALY and £28,971/QALY respectively, whilst testing black Africans plus those from countries with a TB incidence of >20/100,000 (‘middle incidence’, MI) cost £25,218/QALY and £32,410/QALY using TST alone or IGRA alone respectively. NICE, BHIVA, or more extensive strategies, were not cost-effective. (Table) Using PSA, no testing was most likely cost-effective up to £30,000/QALY. In a contemporary HIV population with very high uptake of ART, neither current UK guideline is cost-effective. Testing black Africans, or black Africans and people from middle TB incidence countries appear at best marginally cost-effective. Future UK guidance needs to reflect changing health demographics, improved outcomes for people in HIV care, and clinical pragmatism. Abstract S88 Table 1 Costs for selected strategies, discounted cost/case prevented and cost/QALY gained compared to no testing and last (non-dominated) strategy Strategy Total cost of strategy per 10,000 people living with HIV Cases TB prevented (discounted) QALYs gained compared to no testing (discounted) Cost/case averted Cost/QALY compared to no testing Incremental cost/QALY compared to last strategy BHIVA 2011 £749,274 2.28 1.28 £21,371 £37,952 EXTENDED DOMINANCE TST in BA £749,660 3.9 2.09 £12,566 £23,429 £23,429 TST in BA and MI £761,797 4.49 2.43 £13,614 £25,218 EXTENDED DOMINANCE NICE 2011 £788,037 1.11 0.63 £78,429 £139,281 DOMINATED IGRA in BA £812,048 6.83 3.85 £16,314 £28,971 EXTENDED DOMINANCE IGRA in BA and MI £865,959 9.06 5.1 £18,250 £32,410 EXTENDED DOMINANCE IGRA in all £1,056,702 10.17 5.72 £35,030 £62,209 EXTENDED DOMINANCE NICE 2016 £1,058,522 10.17 5.72 £35,234 £62,571 DOMINATED TST&IGRA in all £1,219,154 10.99 5.88 £47,166 £88,139 EXTENDED DOMINANCE TST&IGRA&CXR&IS in all £1,999,789 20.58 10.44 £63,142 £124,393 EXTENDED DOMINANCE BA - Black African, BHIVA – British HIV Association, CXR – chest X ray, IGRA – Interferon-gamma release assay, IS – induced sputum, MI – middle [TB] incidence countries, NICE – National Institute of Health and Care Excellence, QALY – Quality adjusted life year, TB – tuberculosis (includes active disease and subclinical tuberculosis cases), TST – tuberculin skin test.