Health economic analyses of latent tuberculosis infection screening and preventive treatment among people living with HIV in lower tuberculosis incidence settings: a systematic review

Abstract

Introduction: In lower tuberculosis (TB) incidence countries (<100 cases/100,000/year), screening and preventive treatment (PT) for latent TB infection (LTBI) among people living with HIV (PLWH) is often recommended, yet guidelines advising which groups to prioritise for screening can be contradictory and implementation patchy. Evidence of LTBI screening cost-effectiveness may improve uptake and health outcomes at reasonable cost. Methods: Our systematic review assessed cost-effectiveness estimates of LTBI screening/PT strategies among PLWH in lower TB incidence countries to identify model-driving inputs and methodological differences. Databases were searched 1980-2020. Studies including health economic evaluation of LTBI screening of PLWH in lower TB incidence countries (<100 cases/100,000/year) were included. Results: Of 2,644 articles screened, nine studies were included. Cost-effectiveness estimates of LTBI screening/PT for PLWH varied widely, with universal screening/PT found highly cost-effective by some studies, while only targeting to high-risk groups (such as those from mid/high TB incidence countries) deemed cost-effective by others. Cost-effectiveness of strategies screening all PLWH from studies published in the past five years varied from US$2828 to US$144,929/quality-adjusted life-year gained (2018 prices). Study quality varied, with inconsistent reporting of methods and results limiting comparability of studies. Cost-effectiveness varied markedly by screening guideline, with British HIV Association guidelines more cost-effective than NICE guidelines in the UK. Discussion: Cost-effectiveness studies of LTBI screening/PT for PLWH in lower TB incidence settings are scarce, with large variations in methods and assumptions used, target populations and screening/PT strategies evaluated. The limited evidence suggests LTBI screening/PT may be cost-effective for some PLWH groups but further research is required, particularly on strategies targeting screening/PT to PLWH at higher risk. Standardisation of model descriptions and results reporting could facilitate reliable comparisons between studies, particularly to identify those factors driving the wide disparity between cost-effectiveness estimates. Registration: PROSPERO CRD42020166338 (18/03/2020).

Keywords: HIV; latent tuberculosis; screening; health economic; cost-effectiveness; cost-utility; model; review.

Figure 1.. Flow chart of study selection, showing included studies stratified by World Health Organization region.

The search identified 1627, 1261, and 791 potentially relevant titles from PubMed, Embase, Web of Science, respectively (3679 in total). Eight articles provided model-based cost-effectiveness estimates for the screening for and treatment of latent tuberculosis infection among people living with HIV in lower TB incidence countries and were included in the review. The search was conducted for articles published 1st January 1980 up to the 30 ^th September 2020. PLWH – people living with HIV; TB – tuberculosis. ¹ Higher TB incidence countries defined as ≥150/100,000 cases as of 2018 ). ² Kowada et al. modelled “low TB incidence countries” (defined as <24 cases/100,000) but the majority of the input data are from Japan .

Figure 2.. Forest plot of included study incremental cost-effectiveness ratio estimates (ICERs) adjusted to 2018 prices.

Vertical dashed lines show willingness to pay (WTP) thresholds used in the included papers: US$100,000 ^, , US$50,000, ^{, ,} , £30,000 (converted to US$43,668), and €24,000 (converted to US$29,112) (these thresholds have not been uplifted to 2018 values because thresholds tend to remain fixed rather increasing with inflation). Interventions with cost-effectiveness estimates below a WTP threshold are interpreted as being value for money. Azadi et al. used the 2010 Brazilian GDP per capita (US$11,700) as the WTP threshold . As this represents a more dynamic threshold, the value US$9001 is plotted, representing Brazil’s GDP per capita in 2018 . For Capocci et al. 2020, only the 16 strategies reported in the main publication are shown (excludes no testing scenario and chest X-ray only scenario) . CXR – chest X-ray; MI – middle TB incidence countries (40-300/100,000); NS – not stated; PLWH – people living with HIV; TST - tuberculin skin test; IGRA - interferon-gamma release assays. * “Low TB incidence countries” (majority of data taken from Japan). ** NICE recommendations: use both IGRA and TST if CD4 count <200 cells/mm ³, IGRA with or without concurrent TST if CD4 200-500 cells/mm ³. BHIVA recommendations are to use IGRA test. ICERs shown are 2005-2010 estimates (2000-2005 estimates not shown) . *** Confirm positive strategy: initial TST test, IGRA confirmation for TST positives. Confirm negative strategy: initial IGRA test, TST for all IGRA negatives, positive result on either test indicates LTBI.