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AIDS:
doi: 10.1097/QAD.0b013e3283320dfd
Epidemiology and social

Tuberculosis among people with HIV infection in the United Kingdom: opportunities for prevention?

United Kingdom Collaborative HIV Cohort Study Group

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Author Information

Received 9 June, 2009

Revised 13 August, 2009

Accepted 19 August, 2009

Correspondence to Alison Grant, PhD, FRCP, DTM&H, Clinical Research Unit, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK. Tel: +44 20 7927 2304; fax: +44 20 7637 4314; e-mail: alison.grant@lshtm.ac.uk

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Abstract

Objective: To investigate the incidence of, and risk factors for, tuberculosis among HIV clinic attendees in the United Kingdom.

Design and methods: Observational cohort study of 27 868 individuals in the United Kingdom Collaborative HIV Cohort collaboration, 1996–2005.

Results: Among individuals not taking combination antiretroviral therapy (cART), tuberculosis incidence was considerably higher among individuals of black African vs. white or other ethnicities {incidence rates 9.9 [95% confidence intervals (CIs) 7.2, 12.6], 2.5 [95% CI 1.8, 3.0] and 4.4 [95% CI 2.7, 6.0] episodes per 1000 person-years, respectively}. Tuberculosis incidence decreased with time after starting cART; among black Africans, incidence was consistently higher and remained substantial (5.3 per 1000 person-years) at 24 months and longer after starting cART. The strongest independent risk factors for tuberculosis after cART start were most recent CD4 cell count: adjusted rate ratios (aRR) 10.65 (95% CI 6.11, 18.57), 3.40 (95% CI 2.05, 5.65), 1.77 (95% CI 1.06, 2.96) and 1.84 (95% CI 1.09, 3.12) for individuals with CD4 cell counts less than 50, 50–199, 200–349 and 350–499 cells/μl, respectively, compared with at least 500 cells/μl; and black African vs. white ethnicity [aRR 2.93 (95% CI 1.89, 4.54)]. HIV risk group, shorter time on cART, later calendar period and unsuppressed viral load were also independently associated with incident tuberculosis.

Conclusions: Tuberculosis incidence among people attending UK HIV clinics is substantial, particularly among those with non-white ethnicity and low CD4 cell counts, even after starting cART. Earlier HIV diagnosis is needed in order to implement interventions to prevent tuberculosis; tuberculosis preventive therapy should be considered in addition to cART.

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Introduction

Tuberculosis is the most important cause of HIV-related morbidity and mortality globally, particularly in African countries [1,2]. Black Africans comprise an increasing proportion of individuals accessing HIV care in the United Kingdom (UK) [3]. In London, tuberculosis incidence has more than doubled in the last 15 years [4], reaching 43.2 cases per 100 000 in 2007 (vs. 13.8 per 100 000 in the UK); high tuberculosis incidence is associated with black African ethnicity irrespective of HIV status, and with being born outside the UK [5].

Tuberculosis preventive therapy reduces tuberculosis incidence among HIV-infected people in clinical trials [6] and when given routinely as part of HIV care [7]. It is recommended for HIV-infected individuals in World Health Organization, United States and UK guidelines [8–10]. British HIV Association guidelines do not recommend routine screening for either active or latent tuberculosis, nor make clear recommendations to give preventive therapy [11]. Observational studies show a reduction in tuberculosis incidence among HIV-infected individuals receiving combination antiretroviral therapy (cART) compared with historical cohorts pre-cART [12–16]. However, the incidence of tuberculosis after the start of cART remains appreciable in settings with both high [14] and low tuberculosis incidence [17,18]. High tuberculosis incidence early after initiation of cART may reflect unmasking of active tuberculosis as part of an immune reconstitution syndrome and, particularly in resource-limited settings, the difficulty of diagnosing active tuberculosis in immunosuppressed patients prior to cART.

The aims of this study were to estimate tuberculosis incidence in HIV clinics attendees in the UK before and after initiation of cART, particularly comparing African to non-African individuals; to describe tuberculosis recurrence; and to investigate risk factors for tuberculosis after starting cART.

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Methods

UK Collaborative HIV Cohort study

We used data from the United Kingdom Collaborative HIV Cohort (UK CHIC) study. This is an observational cohort of adults (≥16 years) with HIV infection attending some of the largest HIV clinical centres in the UK, described previously [19] (see Acknowledgements section). Data provided by centres concerning participant demographics, antiretroviral history, laboratory results, AIDS-defining events and deaths are checked and inconsistencies followed up. In this analysis, entry to the UK CHIC study was defined as the latest of date of first attendance at a participating clinic; 16th birthday; or 1 January 1996. During the study period, no participating clinic routinely offered tuberculosis preventive therapy.

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Participants in this analysis

We included adults who entered the UK CHIC study before 1 January 2006. There were no exclusions based on either AIDS-defining events or tuberculosis prior to study entry; or on whether cART was started during the study period. We categorized participants as ‘black African’ and ‘white’ as indicated in clinic records; all other reported ethnicities (and unknown) were categorized as ‘other’.

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Tuberculosis episodes

To determine the overall frequency of tuberculosis among UK CHIC participants, we included episodes of clinical tuberculosis between 1 January 1996 and 30 June 2006, regardless of the timing of the tuberculosis episode in relation to first clinic attendance. Tuberculosis episodes were included if they were recorded as such by study clinics: case definitions were not specified, and laboratory confirmation was not required.

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Individuals and tuberculosis episodes included in the analysis of tuberculosis incidence

We wished to investigate whether clinics had opportunities to deliver interventions to prevent tuberculosis; therefore in the analysis of tuberculosis incidence, we excluded tuberculosis episodes occurring within 3 months of first clinic attendance, assuming that these episodes were diagnosed, or investigations initiated, at the first visit. Correspondingly, we excluded follow-up time during the same 3-month period. We included only the first tuberculosis episode after UK CHIC entry (which was not necessarily the first-ever tuberculosis episode) per participant. If a participant had a tuberculosis episode within 3 months of first clinic attendance, we excluded follow-up time for that individual during the period of tuberculosis treatment (assumed to be 6 months after the tuberculosis episode date). Individuals included in the analysis of tuberculosis incidence required at least one CD4 cell count result (which, among those who developed tuberculosis, had to precede the tuberculosis episode) (Fig. 1).

Fig. 1
Fig. 1
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Tuberculosis episodes were classified as pulmonary or extrapulmonary if specified in clinic records, or unspecified if not.

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Statistical analysis

Statistical analysis was performed using SAS version 9.1 (SAS Institute Inc., Cary, North Carolina, USA). We defined the cART start date as the date that the participant first received a combination of at least three antiretroviral agents: regimens with fewer than three agents were not considered as cART. Any subsequent cART interruptions were ignored.

A participant's first HIV clinic visit may have predated the start of the UK CHIC study (1 January 1996). For the analysis of tuberculosis incidence among participants not taking cART, participants whose first clinic visit was before 1 January 1996 entered the tuberculosis incidence cohort (‘baseline’ for the incidence analysis) on the latest of UK CHIC entry; if an episode of tuberculosis occurred within 3 months of first clinic visit (thus excluded from the incidence analysis), 6 months after the tuberculosis episode date; date of first CD4 cell count. Participants whose first clinic visit was after 1 January 1996 entered the incidence cohort on the latest of 3 months after first clinic visit; if tuberculosis occurred within 3 months of first clinic visit, 6 months after the tuberculosis episode date; date of first CD4 cell count. Follow-up for this analysis was censored at the earliest of the first tuberculosis episode; death; the cART start date; or, for those who did not start cART, the last study visit before 30 June 2006.

To calculate tuberculosis incidence on cART, individuals whose first clinic visit was before 1 January 1996 entered the cohort on the latest of cART start date; 6 months after the start of any tuberculosis episode occurring within 3 months of first clinic visit; first CD4 cell count. Individuals whose first clinic visit was after 1 January 1996 entered the cohort on the latest of cART start date; 3 months after the first clinic visit; 6 months after any tuberculosis episode occurring within 3 months of first clinic visit; first CD4 cell count. Exit from the on-cART incidence cohort ended on the earliest of first tuberculosis episode; death; or last study visit before 30 June 2006. We estimated tuberculosis incidence rates among individuals not taking cART and after starting cART, stratified by ethnic group and time-updated CD4 cell count.

In an analysis restricted to individuals whose first clinic visit was after 1 January 1996, we compared median time from first clinic visit to first tuberculosis episode using Kaplan–Meier methods.

We used Poisson regression to analyse risk factors for tuberculosis among individuals after starting cART, with exclusions as above concerning tuberculosis episodes and follow-up time within 3 months of the first clinic visit. In this analysis we used the most recent CD4 cell count and viral load, updating when new results were recorded. All variables which were significant in univariable analyses at P < 0.20 or were considered a priori to be of clinical importance were included in multivariable analyses.

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Ethical approval

The UK CHIC study was approved by the West Midlands Multicentre Research Ethics Committee.

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Results

Participants and episodes of tuberculosis

Overall, 27 868 individuals (median age 34 years at study entry, 76.3% male) joined UK CHIC before 1 January 2006. Seven hundred and forty-one (2.7%) of these individuals experienced one or more episodes of tuberculosis between 1 January 1996 and 30 June 2006.

Three hundred and sixty-five (49.3%) of the 741 tuberculosis episodes were within 3 months of first clinic visit. Participants with a tuberculosis episode within the first 3 months vs. subsequently were younger (median age at tuberculosis episode 35 vs. 37 years), and more likely to be female (48.8 vs. 33.5%) and of non-white ethnicity (88.8 vs. 60.0%).

Among the 27 868 individuals included in the UK CHIC study, 5035 (18.1%) were excluded from the analysis of tuberculosis incidence, 2521 (9.0%) who were lost to follow-up or died within 3 months of first clinic visit, 1107 (4.0%) who had no CD4 cell count and 1407 (5.0%) who fulfilled both these criteria (Fig. 1). The 22 833 individuals included in the analysis of tuberculosis incidence, compared to the 5035 excluded, were a similar age but more likely to be male (77.2 vs. 72.3%), of white ethnicity (62.1 vs. 48.3%), and to have acquired HIV by sex between men (58.7 vs. 41.2%).

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Analysis of tuberculosis incidence

Twenty-two thousand eight hundred and thirty-three individuals were followed for a total of 112 897 person-years {median follow-up time 4.2 [interquartile range (IQR) 1.7, 8.2] years}. Of these, 5136 (22.5%) were black African, 14 169 (62.1%) white and 3528 (15.5%) of other ethnicities. The characteristics of these individuals at study baseline, stratified by ethnic group, are shown in Table 1. The median age at study entry was 35 years; this was similar in all ethnic groups. Black African individuals were more likely than white or other to be female (63.9 vs. 7.9 vs. 22.8%, P < 0.0001, χ2 test), to have acquired HIV infection by heterosexual sex (89.4 vs. 9.9 vs. 33.2%, P < 0.0001, χ2 test), and to have first visited a study clinic in later calendar periods (52.0 vs. 29.1 vs. 42.4% in 2002–2005, P < 0.0001). The CD4 cell count at entry to the incidence cohort was lower in individuals of black African than white or other ethnicities (median 265 vs. 356 vs. 330 cells/μl, P < 0.0001, Kruskal–Wallis test). Black African individuals had a greater proportion of follow-up time after starting cART with CD4 cell counts below 200 cells/μl (21.6% vs. 15.9% in white vs. 16.4% in other individuals).

Table 1
Table 1
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Three hundred and seventy individuals experienced one or more tuberculosis episodes later than 3 months after first clinic visit, giving a rate of 3.28 per 1000 person-years [95% confidence interval (CI) 2.94, 3.61]. Tuberculosis incidence rates were 8.45 (7.16, 9.73), 1.89 (1.58, 2.19) and 3.75 (2.78, 4.73) per 1000 person-years among individuals of black African, white and other ethnicities, respectively (Table 1). The median (IQR) CD4 cell count at the time of the first tuberculosis episode was 192, 153 and 230 cells/μl for black African, white and other ethnicities, respectively (P = 0.32, Kruskal–Wallis test). Restricting the analysis to 15 776 individuals entering the UK CHIC study after 1 January 1996, the median time from first clinic visit to first tuberculosis episode was 9.0, 13.1 and 16.3 months among individuals of black African, white and other ethnicities, respectively, based on Kaplan–Meier estimates.

Recurrent tuberculosis within the study period was least common in white individuals [17/166 (10.2%) vs.12/147 (8.8%) vs. 9/57 (15.8%) for black African vs. white vs. other ethnicities, P = 0.001] (Table 1).

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Tuberculosis incidence among individuals not taking combination antiretroviral therapy

Overall, 38 440 person-years were contributed by 15 607 individuals not taking cART, with a median duration of follow-up of 4.8 (IQR 1.9, 9.5) years. Figure 2 shows tuberculosis incidence, stratified by ethnic group and CD4 cell count: it was substantially higher among black African than white or other ethnic groups, being 9.9 (95% CI 7.2, 12.6), 2.5 (95% CI 1.8, 3.0) and 4.4 (95% CI 2.7, 6.0) episodes per 1000 person-years, respectively. Tuberculosis incidence was higher at lower CD4 cell counts in all ethnic groups: rates were 51.1 (95% CI 23.4, 97.1), 10.6 (95% CI 4.8, 20.1) and 11.9 (95% CI 2.5, 34.8) per 1000 person-years among black African, white and other individuals with a most recent CD4 cell count below 50 cells/μl, respectively, compared to 4.5 (95% CI 1.8, 9.3) 0.3 (95% CI 0.1, 0.9) and 0.5 (95% CI 0.0, 2.6) per 1000 person-years, respectively, for individuals with CD4 cell counts of 500 and above.

Fig. 2
Fig. 2
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Tuberculosis incidence after starting combination antiretroviral therapy

Among 7181 participants who started cART, there were 226 first episodes of tuberculosis during 74 457 person-years [incidence rate 3.0 per 1000 person-years, 95% CI 2.6, 3.4; median duration of follow-up 3.3 (IQR 1.5, 5.9) years]. Tuberculosis incidence rates by time since starting cART, stratified by ethnic group, are shown in Fig. 3. The incidence of tuberculosis decreased with increasing time after starting cART, from 13.3 per 1000 person-years in the first 3 months to 1.8 per 1000 person-years more than 24 months after starting cART (Fig. 3). Tuberculosis incidence rates were consistently higher among black African individuals who started cART and remained substantial (5.3 per 1000 person-years) even after 24 months of cART.

Fig. 3
Fig. 3
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Risk factors for tuberculosis among individuals after starting combination antiretroviral therapy

In univariable analysis (Table 2), younger age, female sex, non-white ethnicity, heterosexual exposure to HIV, lower CD4 cell count, shorter time since starting cART, HIV viral load at least 50 copies/ml and earlier calendar period were all associated with higher risk of incident tuberculosis after starting cART. In a multivariable analysis after adjustment for these variables, most recent CD4 cell count remained the strongest risk factor for incident tuberculosis with adjusted rate ratios (aRRs) of 10.65 (95% CI 6.11–18.57), 3.40 (95% CI 2.05, 5.65), 1.77 (95% CI 1.06, 2.96) and 1.84 (95% CI 1.09, 3.12) for individuals with CD4 cell counts of less than 50, 50–199, 200–349 and 350–499 cells/μl, respectively, compared with 500 cells/μl or greater. Black African ethnicity remained associated with an elevated risk of tuberculosis, with an aRR of 2.93 (95% CI 1.89, 4.54) compared to white individuals. Compared with sex between men, there was a higher risk of tuberculosis among heterosexually exposed men (aRR 1.87, 95% CI 1.17, 3.00) and nonheterosexually exposed women (aRR 2.06, 95% CI 1.10, 3.87). Tuberculosis incidence reduced with time after initiation of cART with an aRR of 0.49 (95% CI 0.34, 0.69) for the period 2.1–4 vs. 2 or fewer years after starting cART, and was lower among individuals with a most recent HIV viral load below 50 copies/ml (aRR 0.70, 95% CI 0.52, 0.94). Tuberculosis incidence was also higher, in adjusted analyses, in more recent calendar periods (Table 2).

Table 2
Table 2
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Among 164 individuals who started cART at least 6 months prior to their tuberculosis episode (and therefore had sufficient time to achieve virological suppression), 147 (89.6%) had a viral load estimation within 3 months of the episode. Seventy-eight (53%) of these had a viral load less than 50 copies/ml.

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Discussion

The analysis highlights the substantial and increasing importance of tuberculosis as a cause of HIV-related disease in the UK, particularly among black African individuals. Nearly half of all tuberculosis episodes occurred within 3 months of the first clinic visit; a diagnosis of tuberculosis may have prompted HIV testing, or active tuberculosis may have been diagnosed at assessment after a first positive HIV test. We found a very strong association between CD4 cell count and risk of incident tuberculosis after cART start; this was stronger than in some previous studies [14,17,20], probably because we used the most recent rather than the baseline CD4 cell count. The association between non-white (particularly black African) ethnicity and tuberculosis persisted after adjustment for CD4 cell count, consistent with the epidemiology of tuberculosis in the UK [5]. The high risk of tuberculosis among black African migrants attending HIV clinics is most likely attributable to a combination of a higher risk of previous tuberculosis exposure and thus of tuberculosis infection, compounded by lower CD4 cell counts at study entry and after the start of cART.

Consistent with previous reports from HIV clinic settings [14,17,18,21], tuberculosis incidence fell with increasing time after starting cART; however, it remained substantial in individuals of non-white ethnicity even after 24 months. The decrease in incidence with time after starting cART is expected as the CD4 cell count increases, but the continuing risk is consistent with other data. Tuberculosis incidence among the non-UK born falls with increasing time in the UK; however, half of tuberculosis cases in the non-UK born are diagnosed more than 5 years after arrival [22]. This, along with a relatively long median time between cohort entry and first tuberculosis episode, suggests an opportunity for HIV clinics to deliver interventions to prevent tuberculosis. For individuals found to have HIV infection only after the diagnosis of active tuberculosis, this opportunity has largely been missed, since transmission of tuberculosis within the UK is relatively unusual and hence recurrence after successful treatment unlikely [23]. There is a clear need for earlier diagnosis of HIV infection, so that cART can be started before CD4 cell counts have fallen to very low levels, reducing the risk of tuberculosis and other HIV-related morbidity.

In addition to timely initiation of cART, HIV clinics should screen new patients for active tuberculosis, implement infection control measures, and offer tuberculosis preventive therapy, particularly to migrants from settings of high tuberculosis prevalence, in line with UK tuberculosis control guidelines [10]. Individuals with evidence suggesting latent tuberculosis infection should be targeted for preventive therapy since there is much stronger evidence of benefit among these individuals [6]. Data from Brazil suggest that implementation of isoniazid preventive therapy and cART reduces tuberculosis incidence by more than cART alone [24], consistent with the different mechanisms of action of the two interventions. Practical issues concerning preventive therapy for HIV-infected individuals which remain to be resolved include how best to exclude active tuberculosis, although this is not a major obstacle in well resourced settings. The tuberculin skin test is a good marker of subsequent risk of active tuberculosis, but imposes logistical obstacles. Interferon gamma release assays for tuberculosis are now commercially available but more data are needed to determine how accurately these tests identify individuals at highest risk of progression to active tuberculosis [25], especially among individuals from regions with high tuberculosis prevalence [26]. Interferon gamma release assays are more likely to give indeterminate results among those with low CD4 cell counts, exactly those at highest risk of tuberculosis.

By excluding tuberculosis episodes within 3 months after the first clinic visit, our estimates of tuberculosis ‘incidence’ are lower than had these episodes been included, and this is relevant to comparisons with other cohorts if a similar exclusion was not made. The excluded cases arguably represent tuberculosis which was prevalent at the time of clinic entry, rather than true incident disease; interventions to prevent these episodes could only be delivered by HIV clinics if individuals were diagnosed and enrolled in care earlier. The tuberculosis incidence rates in this study should be regarded as minimum estimates: firstly, we censored follow-up after the first tuberculosis episode in the study period and hence recurrent episodes were excluded. Secondly, despite attempts to minimize missing data, clinics may not record every disease episode. Incomplete recording of tuberculosis episodes would only affect our conclusions if completeness varied by key exposure variables such as ethnic group or CD4 cell count. Tuberculosis episodes occurring at the time of HIV diagnosis might be more likely to be recorded, and these were more frequent in black Africans: however, such episodes were excluded from the analysis of tuberculosis incidence and hence would not affect the comparison of incidence by ethnic group.

In conclusion, tuberculosis is a major cause of morbidity among HIV clinic attendees, particularly those with low CD4 cell counts and of non-white ethnic group. Tuberculosis incidence falls gradually with increasing time after starting cART but remains high, especially in individuals with low CD4 cell counts and of black African ethnicity. Earlier HIV diagnosis is needed so that cART can be started before individuals become at high risk of tuberculosis; tuberculosis preventive therapy should be recommended for individuals with evidence of latent tuberculosis infection.

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Acknowledgements

UK CHIC Study Group Writing Committee: Alison D. Grant (Clinical Research Unit, London School of Hygiene & Tropical Medicine, London), Loveleen Bansi (Research Department of Infection & Population Health, University College Medical School, London), Jonathan Ainsworth (North Middlesex University Hospital NHS Trust, London), Jane Anderson (Homerton University Hospital NHS Trust, London), Valerie Delpech (Health Protection Agency Centre for Infections, London), Philippa Easterbrook (King's College Hospital NHS Trust, London), Martin Fisher (Brighton and Sussex University Hospitals NHS Trust), Brian Gazzard (Chelsea and Westminster NHS Trust, London), Richard Gilson (UCL Medical School and Mortimer Market Centre, Camden Primary Care Trust, London), Mark Gompels (North Bristol NHS Trust, Bristol), Teresa Hill (Research Department of Infection & Population Health, University College Medical School, London), Margaret Johnson (Royal Free NHS Trust, London), Clifford Leen (The Lothian University Hospitals NHS Trust, Edinburgh), Chloe Orkin (Barts and The London NHS Trust, London), Andrew N. Phillips (Research Department of Infection & Population Health, University College Medical School, London), Kholoud Porter (Medical Research Council Clinical Trials Unit, London), Frank Post (King's College Hospital NHS Trust, London), John Walsh (Imperial College Healthcare NHS Trust, London), Caroline A. Sabin (Research Department of Infection & Population Health, University College Medical School, London).

Author contributions: Alison Grant: study concept and design, contribution to analyses, drafting manuscript; Loveleen Bansi: study design and analysis, data management and quality control, drafting manuscript; Jonathan Ainsworth: site coordination, review of manuscript; Jane Anderson: site coordination, review of manuscript; Valerie Delpech: data management and quality control, review of manuscript; Philippa Easterbrook: site coordination, review of manuscript; Martin Fisher: site coordination, review of manuscript; Brian Gazzard: site coordination, review of manuscript; Richard Gilson: site coordination, review of manuscript; Mark Gompels: site coordination, review of manuscript; Teresa Hill: data management and quality control, review of manuscript; Margaret Johnson: site coordination, review of manuscript; Clifford Leen: site coordination, review of manuscript; Chloe Orkin: site coordination, review of manuscript; Andrew N. Phillips: UK CHIC design, review of manuscript; Kholoud Porter: UKCHIC design, review of manuscript; Frank Post: site coordination, review of manuscript; John Walsh: site coordination, review of manuscript; Caroline A. Sabin: study design and analysis, drafting manuscript. All authors have contributed to the interpretation of the results, provided critical input into and approved the final version of the manuscript prior to submission for publication.

Richard Gilson, Martin Fisher, Andrew Phillips, Kholoud Porter, Brian Gazzard, Philippa Easterbrook, David Dunn and Caroline Sabin contributed to the original design of the UK CHIC Study and obtained study funding. Richard Gilson, Achim Schwenk, Clifford Leen, Jane Anderson, Brian Gazzard, Margaret Johnson, Philippa Easterbrook, John Walsh, Martin Fisher and Chloe Orkin contributed to the ongoing collection of data and continued quality control.

UK CHIC Steering Committee: Jonathan Ainsworth, Jane Anderson, Abdel Babiker, Valerie Delpech, David Dunn, Philippa Easterbrook, Martin Fisher, Brian Gazzard (Chair), Richard Gilson, Mark Gompels, Teresa Hill, Margaret Johnson, Clifford Leen, Chloe Orkin, Andrew Phillips, Deenan Pillay, Kholoud Porter, Caroline Sabin, Achim Schwenk, John Walsh.

Central co-ordination: Research Department of Infection & Population Health, University College Medical School, London (Loveleen Bansi, Teresa Hill, Andrew Phillips, Caroline Sabin); Medical Research Council Clinical Trials Unit (MRC CTU), London (David Dunn, Adam Glabay, Kholoud Porter).

Participating centres: Barts and The London NHS Trust, London (Chloe Orkin, Kevin Jones, Rachel Thomas); Brighton and Sussex University Hospitals NHS Trust (Martin Fisher, Nicky Perry, Stuart Tilbury, Duncan Churchill); Chelsea and Westminster NHS Trust, London (Brian Gazzard, Steve Bulbeck, Sundhiya Mandalia, Jemima Clarke); Health Protection Agency Centre for Infections London (Valerie Delpech); Homerton University Hospital NHS Trust, London (Jane Anderson, Sajid Munshi); King's College Hospital NHS Trust, London (Philippa Easterbrook, Frank Post, Yasar Khan, Paragi Patel, Fatimah Karim, Stephen Duffell); Medical Research Council Clinical Trials Unit (MRC CTU), London (Abdel Babiker, David Dunn, Adam Glabay, Kholoud Porter); Mortimer Market Centre, University College London Medical School, London (Richard Gilson, Shuk-Li Man, Ian Williams); North Bristol NHS Trust (Mark Gompels, Debbie Dooley); North Middlesex University Hospital NHS Trust, London (Achim Schwenk, Jonathan Ainsworth, Chris Wood); University College London Medical School (Royal Free Campus) and Royal Free NHS Trust, London (Margaret Johnson, Mike Youle, Fiona Lampe, Colette Smith, Helen Grabowska, Clinton Chaloner, Dewi Ismajani Puradiredja, Loveleen Bansi, Teresa Hill, Andrew Phillips, Caroline Sabin); Imperial College Healthcare NHS Trust, London (Nicky Mackie, Alan Winston, Jonathan Weber, Christian Kemble, Mark Carder, John Walsh); The Lothian University Hospitals NHS Trust, Edinburgh (Clifford Leen, Alan Wilson).

Funding: Alison Grant was supported by a Public Health Career Scientist award from the UK Department of Health. The UK CHIC Study is funded by the Medical Research Council, UK (grant G0000199 and G0600337). The views expressed in this manuscript are those of the researchers and not necessarily those of the Medical Research Council.

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Meda, ZC; Sombie, I; Sanon, OWC; Mare, D; Morisky, DE; Chen, YMA
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Risk of tuberculosis following HIV seroconversion in high-income countries
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10.1136/thoraxjnl-2012-201740
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Comparison of screening strategies to improve the diagnosis of latent tuberculosis infection in the HIV-positive population: a cohort study
Pollock, KM; Tam, H; Grass, L; Bowes, S; Cooke, GS; Pareek, M; Montamat-Sicotte, D; Kapembwa, M; Taylor, GP; Lalvanil, A
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Incidence and Risk Factors for Tuberculosis in People Living with HIV: Cohort from HIV Referral Health Centers in Recife, Brazil
Batista, JDL; de Albuquerque, MDPM; Maruza, M; Ximenes, RAD; Santos, ML; Montarroyos, UR; Miranda-Filho, DD; Lacerda, HR; Rodrigues, LC
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Keywords:

antiretroviral therapy; HIV infection; tuberculosis; United Kingdom

© 2009 Lippincott Williams & Wilkins, Inc.

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