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Screening for Latent Tuberculous Infection in People Living with HIV Infection in Auckland, New Zealand

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Screening for Latent Tuberculous Infection in People Living with HIV Infection in Auckland, New Zealand INT J TUBERC LUNG DIS 21(9):1008–1012 Q 2017 The Union http://dx.doi.org/10.5588/jtld.17.0103 Screening for latent tuberculous infection in people living with HIV infection in Auckland, New Zealand N. Gow, S. Briggs, M. Nisbet Department of Infectious Diseases, Auckland City Hospital, Auckland, New Zealand SUMMARY SETTING: New Zealand, which has a low incidence of RESULTS: Of the 752 patients from the initial cohort, tuberculosis (TB), has historically taken a risk-based 416 (55%) had documentation of LTBI screening, which approach to screening for latent tuberculous infection was positive in 74 (10%): 19/461 (4%) low-risk and 55/ (LTBI) in adult people living with the human immuno- 291 (19%) high-risk patients. LTBI treatment was deficiency virus infection (PLHIV). received in 13 low-risk and 44 high-risk patients. Of OBJECTIVE: To evaluate LTBI screening, treatment and 73 patients in the second cohort, 68 (93%) were outcomes in an adult PLHIV population. screened. DESIGN: This was a retrospective clinical record review CONCLUSION: LTBI screening was incomplete in our of an initial cohort of adult PLHIV attending the clinic, but improved between 2011 and 2014. A Auckland City Hospital HIV clinic in 2011, and a significant number of patients with LTBI did not second cohort of adult PLHIV newly attending the clinic originate from a high TB incidence country. in 2014. We analysed high-risk (born in or acquiring KEY WORDS: PLHIV; high-income countries; screen- HIV in a high TB incidence country) and low-risk ing; IGRA patients using descriptive statistical methods. TUBERCULOSIS (TB) IS A LEADING cause of notified with active TB disease and 3.5% of PLHIV morbidity and mortality in people living with the cared for at Auckland City Hospital (ACH).9 The human immunodeficiency virus infection (PLHIV).1 most recent New Zealand guidelines for TB control, Latent tuberculous infection (LTBI) is a state of from 2010, recommend that all adult PLHIV be persistent immune response to stimulation by Myco- screened for LTBI using the tuberculin skin test (TST) bacterium tuberculosis antigens with no evidence of or an interferon-gamma release assay (IGRA).10 The active TB disease.2 Following exposure to TB, PLHIV decision to screen for LTBI at ACH is at the discretion are at higher risk of developing LTBI and of of the treating physician. The QuantiFERONw-TB progressing from LTBI to active TB disease. Intensi- Gold (QFN; Cellestis Limited, Carnegie, VIC, Aus- fied TB case finding is one of the key World Health tralia) IGRA has been the preferred screening test for Organization (WHO) strategies to reduce the burden all adult PLHIV at ACH, regardless of CD4 count, of TB in PLHIV.3,4 LTBI treatment reduces the since its introduction in 2006. incidence of active TB disease among PLHIV, We aimed 1) to determine the extent of LTBI resulting in a 33% risk reduction for all PLHIV and screening for adult PLHIV attending the ACH HIV a 64% risk reduction in those with a positive LTBI clinic in 2011, 2) to review LTBI treatment and screening test.5 The most recent WHO guidelines on outcomes, and 3) to re-evaluate LTBI screening in the the management of LTBI in high- or upper middle- cohort of adult PLHIV newly attending the ACH HIV income countries strongly recommend systematic clinic in 2014. Our goal is to adhere to WHO LTBI screening in PLHIV and LTBI treatment for recommendations and perform LTBI screening those with a positive LTBI screening test.6,7 among all adult PLHIV, and to treat where appro- The notification rate of active TB disease in New priate. Zealand was 7.0 per 100 000 population in 2011.8 A recently published audit of HIV and TB in Auckland, METHODS New Zealand, identified 40 patients with HIV- associated active TB disease diagnosed between ACH is the tertiary referral centre for all PLHIV in the 1997 and 2009, representing 1.6% of all patients Auckland and Northland regions, serving an adult Correspondence to: Nick Gow, Department of Medicine, North Shore Hospital, Taharoto Road, Auckland, New Zealand. e-mail: [email protected] Article submitted 16 February 2017. Final version accepted 29 May 2017. LTBI screening in Auckland, New Zealand 1009 Table 1 Patient characteristics (initial cohort) Born/acquired HIV in high Born/acquired HIV in low All TB incidence country TB incidence country (n ¼ 752) (n ¼ 291) (n ¼ 461) n (%) n (%) n (%) Age, years, median 46 43 49 Female 139 (18) 106 (36) 30 (7) MSM mode of transmission 440 (59) 65 (22) 375 (81) CD4 count at presentation, cells/mm3, median 343 290 376 Receiving antiretroviral therapy 644 (86) 245 (84) 399 (87) HIV viral load , 1.3 log copies/ml 496 (66) 190 (65) 281 (61) First seen in clinic: 1990–2005 390 (52) 151 (51) 239 (52) 2006–2011 362 (48) 140 (48) 222 (48) HIV ¼ human immunodeficiency virus; TB ¼ tuberculosis; MSM ¼ men who have sex with men. population of approximately 1.1 million.11 This excluded, leaving 752 for analysis. The most common study analysed two study cohorts: the initial cohort modes of transmission of HIV infection were via men consisted of all adult PLHIV attending the ACH HIV who had sex with men (MSM) (n ¼ 439), heterosex- clinic in 2011 who had been seen at two or more ual (n ¼ 244), injecting drug use (IDU) (n ¼ 10), IDU clinic visits; the second cohort was made up of all or MSM (n¼8), blood transfusion (n¼3), needlestick adult PLHIV newly attending the ACH HIV clinic in injury (n ¼ 1), and perinatal (n ¼ 1), and was 2014 who had been seen at two or more clinic visits. unknown in 46. Self-reported ethnicity was as The clinical records of all eligible adult PLHIV follows: NZ European (n ¼ 358), African (n ¼ 146), were reviewed. In the initial cohort, we established NZ Maori (n ¼ 59), South-East Asian (n ¼ 53), demographic information, LTBI screening test results European (n ¼ 49), Pacific Islander (n ¼ 32), East/ before July 2012, LTBI treatment and clinical South Asian (n ¼ 25), Australian (n ¼ 11), North outcomes. TST was performed by injecting 5 tuber- American (n ¼ 9), South American (n ¼ 5), other (n ¼ culin units (0.1 ml) of purified protein derivative 3), and not stated (n ¼ 2). Additional patient intradermally into the flexor surface of the upper characteristics are shown in Table 1. Four hundred forearm, with reading performed after 72 h. A and sixteen (55%) patients underwent LTBI screening positive TST was defined as a skin reaction of 75 on at least one occasion, with a median duration of 44 mm diameter. The ACH Laboratory reports QFN months after the first screening test until July 2012. A results as positive (70.45 international units [IU]/ml positive LTBI screen was found in 74 (10%): 44 with TB-Nil), negative (60.25 IU/ml TB-Nil), equivocal QFN, and 30 with the TST (Figure A). (0.25–0.45 IU/mL TB-Nil, where due to the inherent assay variability the qualitative interpretation of the High tuberculosis incidence subset assay may change on repeat testing) or indeterminate. In the initial cohort, 291 (39%) adult PLHIV had We defined a country with high TB incidence as .20/ been born in or acquired HIV infection in a high TB 100 000 cases/year.12 The extent of LTBI screening incidence country. Two hundred and thirty-eight was then re-assessed in the second cohort. (82%) underwent LTBI screening (Figure B) using The choice of LTBI treatment was at the discretion QFN (n ¼ 135), TST (n ¼ 90) or QFN and TST (n ¼ of the treating physician. LTBI treatment was 13). A positive screen was found in 55 patients (i.e., considered complete if at least 6 months of isoniazid 23% of those screened, or 19% of the total), 29 with (INH) or 4 months of rifampicin (RMP) was given. the TST and 26 with QFN. The median induration of Two-tailed Fisher’s exact test was used to analyse the TSTwas 14.5 mm in the 24 patients for whom this categorical data. result was recorded. Of the 13 patients screened using Institutional ethics approval was granted by the both TST and QFN, 7 had concordant negative Auckland City Hospital Research Office, Auckland, results, 2 had concordant positive results, and 4 had New Zealand, in 2012. discordant results, with 2 initially TST-positive and 2 initially QFN-positive. Of the 55 patients who screened positive, 44 RESULTS underwent LTBI treatment; 1 refused treatment, 1 Initial cohort died before commencing treatment, and in 3 cases After exclusion of six patients seen at the clinic only treatment was deferred due to inconsistent LTBI once, 789 adult PLHIV were under regular review. screening results; the remaining 6 patients, 5 with The median duration of clinic attendance until July positive TST results and 1 with a positive QFN result, 2012 was 81 months (range 7–255). Thirty-seven had did not receive LTBI treatment. In each case, this a previous diagnosis of active TB disease and were appeared to be because the result of their LTBI screen 1010 The International Journal of Tuberculosis and Lung Disease Figure Number and percentage of patients undergoing LTBI screening and LTBI treatment in the initial and follow-up cohorts. A) Initial cohort (all, n ¼ 752); B) initial cohort (high TB incidence country, n¼291); C) initial cohort (low TB incidence country, n¼461); D) follow-up cohort (all, n¼ 73). LTBI ¼ latent tuberculous infection. was missed; the five missed TST results occurred treatment was started. The other patient underwent a before electronic reporting of laboratory results in second QFN test, as the patient’s HIV clinician was 2003, and the missed QFN result was only visible in a unaware of the first test result (this was only available separate encoded electronic reporting system.
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