Missed opportunities for tuberculosis prevention among patients accessing a UK HIV service

Abstract

United Kingdom guidelines recommend screening for and treatment of latent tuberculosis infection (LTBI) in HIV-positive patients at high risk of active tuberculosis (TB) disease, but implementation is suboptimal. We investigated potential missed opportunities to identify and treat LTBI among HIV-positive patients accessing a large HIV outpatient service in London. Case records of all adult patients attending our service for HIV care diagnosed with active TB between 2011 and 2015 were reviewed to determine whether they met criteria for LTBI screening and whether screening was undertaken. Twenty-five patients were treated for TB. Of 15 (60%) patients who started TB treatment ≥6 months after HIV diagnosis, 14 (93%) met UK guideline-recommended criteria for LTBI screening and treatment; only one (7%) had been screened for LTBI. Eight of these 15 (53%) patients had additional risk factors for TB which are not reflected in current UK guidelines. Of 15 patients treated for TB ≥6 months after diagnosis of HIV, 14 (93%) had not been screened for LTBI, suggesting missed opportunities for TB prevention. People living with HIV may benefit from a broader approach to LTBI screening which takes into account additional recognised TB risk factors and ongoing TB exposure.

Keywords

HIV infection tuberculosis latent tuberculosis tuberculosis/prevention and control preventive therapy interferon-gamma release assays

Background

People living with HIV are at high risk of developing active tuberculosis (TB).¹ Screening for and treatment of latent TB infection (LTBI) in selected HIV-positive patients is effective and cost effective^2,3 and is recommended by the British HIV Association (BHIVA) for patients at high risk of TB reactivation, defined by CD4 cell count, duration of antiretroviral therapy (ART) and TB incidence of their region of origin⁴ (Table 1). However, a recent evaluation found that only 57.4% of UK geographical areas offer screening.⁵

Table 1.

Summary of British HIV Association 2011 guidelines for screening and treatment of latent tuberculosis infection in HIV-infected persons.⁴

Tuberculosis prevalence of region of origin^a	Criteria for latent tuberculosis screening according to British HIV Association guidelines	Recommendation if criteria are met
Low (including UK, Western Europe, Australia, USA, Canada and New Zealand)	On ART for less than six months and CD4 cell count < 350 cells/mm³	Screen for latent tuberculosis infection using interferon-gamma release assay and provide chemo-preventative therapy if positive
Medium (including Eastern Europe, Central Asia, North Africa and the Middle East, South Asia, East Asia and the Caribbean)	On ART for less than two years and CD4 cell count < 500 cells/mm³
High (sub-Saharan Africa)	On ART for less than two years

ART: antiretroviral therapy.

^aNumerical definitions of ‘low’/‘medium’/‘high’ incidence not included in the guidelines.

In our UK HIV clinic, 33% of patients originate from high- or medium-TB incidence regions. We introduced a policy of LTBI screening and treatment according to BHIVA guidelines in 2011, but an audit in 2015 revealed only 12.1% screening completion.⁶ We retrospectively reviewed case notes of HIV patients diagnosed with TB, to investigate whether there were missed opportunities to identify and treat LTBI.

Methods

Adults (≥18 years) attending our service for HIV care and diagnosed with TB in 2011–2015 were included. TB cases were identified from the Public Health England London TB Register and from our microbiology service’s database. Patients were classified into two groups according to the time between HIV diagnosis and TB treatment start date: ‘early’ (less than six months), or ‘late’ (six months or more), assuming that TB episodes starting less than six months after HIV diagnosis probably could not have been averted by screening and treatment of LTBI. We compared our clinic practice with 2011 BHIVA guidance.⁴

Results

We identified 25 patients diagnosed with TB between 2011 and 2015 (Table 2). Twelve (48%) were from high-, four (16%) from medium- and nine (36%) from low-TB incidence regions of origin. Time between HIV diagnosis and TB treatment start date ranged from minus five days to 27 years. Ten (40%) had TB ‘early’ (less than six months after HIV diagnosis).

Table 2.

Characteristics of HIV-positive individuals with tuberculosis.

Group			Early	Late
Time between HIV diagnosis and TB episode			<6 months (N=10)	≥6 months (N=15)
Time between HIV diagnosis and TB episode, median (range)			10.5 days(−5 to 125 days)	4.6 years(1.1–26.9 years)
Male, n (%)			5 (50%)	10 (67%)
Age (years), median (range)			47 (24–56)	42 (29–59)
Risk factors for TB infection	Region of origin^a	Low TB incidence	2 (20%)	7 (47%)
		Medium TB incidence	2 (20%)	2 (13%)
		High TB incidence	6 (60%)	6 (40%)
	Other TB riskfactors	Extensive travel/residence inhigh-incidence area	1 (10%)	2 (13%)
		TB contact	0 (0%)	3 (20%)
		Healthcare worker	1 (10%)	2 (13%)
		Intravenous drug use	0 (0%)	2 (13%)
		Previous/current prison resident	0 (0%)	2 (13%)
		Homelessness	1 (10%)	1 (7%)
		At least one of these‘other’ risk factors	3 (30%)	8 (53%)
	At least one of these risk factors for TB infection^b		9 (90%)	12 (80%)
CD4 cell count at start of TB episode (cells/mm³), median (range)			110 (0–310)	480 (20–570)
On antiretroviral therapy at start of TB episode			3 (30%)	6 (40%)
Diagnosed with TB during/following an inpatient admission			9 (90%)	9 (60%)

TB: tuberculosis.

^aDefinitions of low, medium and high incidence follow British HIV Association guidance.⁴

^bIncludes high- or medium-TB incidence region of origin, and additional risk factors listed in the table. Several patients had more than one risk factor.

‘Early’ TB

Of ten patients, eight (80%) were from medium- or high-TB incidence regions. At TB diagnosis median CD4 cell count was 110 (range 0–310) cells/mm³. Nine (90%) were diagnosed with TB during or following inpatient admissions. Eight (80%), all from medium- or high-incidence regions, had TB symptoms at the time of HIV diagnosis. The remaining two developed ‘unmasking’ immune reconstitution inflammatory syndrome following ART initiation.

‘Late’ TB

Of 15 patients, eight (53%) were from high- or medium-TB incidence regions. Additionally, nine (60%) had at least one other recognised TB risk factor, such as healthcare work or time spent in prison (Table 2). Six (40%) were on ART at the time of TB diagnosis, for a median of 2.6 years (range 219 days–9.9 years), all virologically suppressed. Median CD4 cell count was 480 (range 20–570) cells/mm³. Nine (60%) were diagnosed during or following an inpatient admission. Fourteen (93%) patients successfully completed TB therapy, but one died of disseminated TB.

Missed opportunities for LTBI diagnosis and treatment

Of the ‘late’ TB group, 14 (93%) met criteria for LTBI screening and treatment at some point following HIV diagnosis. The individual who did not was from a low-incidence region but did have other TB risk factors (extensive travel to high-incidence countries and previous imprisonment). Only one had LTBI screening performed. He had a negative Quantiferon Gold interferon-gamma release assay (IGRA) one month after HIV diagnosis, when his CD4 cell count was 60 cells/mm³; he remained at potential risk of TB exposure after screening. He was diagnosed with culture-positive pleural TB one year later.

Discussion

In our HIV service, TB continues to cause morbidity (72% inpatient admission rate) and occasionally mortality. Despite most patients who developed ‘late’ TB meeting the 2011 BHIVA criteria for LTBI screening, most were not screened (in keeping with our previous audit⁶). Prompts have been included in the electronic patient record to promote LTBI screening, but our impression is that these remain underutilised. One potential barrier to clinicians initiating screening is that the 2011 BHIVA guidelines are complex, requiring integration of information about CD4 cell count, ART history and region of origin. The 2017 draft BHIVA guidelines recommend a simplified approach which may be easier to implement.⁷

Many patients, including the one who did not otherwise meet screening criteria, had additional risk factors for TB infection, suggesting that selection of patients for LTBI screening may need to take account of risk factors beyond HIV stage and region of origin. This is the approach taken by the 2017 draft guideline.⁷

Even with increased LTBI screening at enrolment in HIV care, it is unlikely that all ‘late’ cases of TB were preventable. IGRA sensitivity for LTBI is not 100%.⁸ Furthermore, some patients developed TB many years after their HIV diagnosis and/or had risk factors suggesting ongoing TB exposure, which may require different strategies.

Several patients had inconsistent concordance with care and might not have taken preventative therapy even if offered; although TB preventative treatment does confer additional benefits to ART alone, optimising HIV treatment in this group might also have reduced TB incidence.^9–11 While beyond the scope of this audit, earlier HIV diagnosis might also have averted TB morbidity for the eight (32%) patients whose TB and HIV diagnoses were essentially simultaneous (less than a two-month interval), and who all had CD4 cell count < 350 cells/mm³ at diagnosis.

Conclusions

There are missed opportunities for LTBI screening in our HIV service, and improving coverage of those at highest risk could reduce morbidity and mortality. People living with HIV may benefit from an approach to LTBI screening which incorporates broader TB risk factors and ongoing TB exposure.

Footnotes

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

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