Dataset Information

Economic and modeling evidence for tuberculosis preventive therapy among people living with HIV: A systematic review and meta-analysis.

ABSTRACT:

Background

Human immunodeficiency virus (HIV) is the strongest known risk factor for tuberculosis (TB) through its impairment of T-cell immunity. Tuberculosis preventive treatment (TPT) is recommended for people living with HIV (PLHIV) by the World Health Organization, as it significantly reduces the risk of developing TB disease. We conducted a systematic review and meta-analysis of modeling studies to summarize projected costs, risks, benefits, and impacts of TPT use among PLHIV on TB-related outcomes.

Methods and findings

We searched MEDLINE, Embase, and Web of Science from inception until December 31, 2020. Two reviewers independently screened titles, abstracts, and full texts; extracted data; and assessed quality. Extracted data were summarized using descriptive analysis. We performed quantile regression and random effects meta-analysis to describe trends in cost, effectiveness, and cost-effectiveness outcomes across studies and identified key determinants of these outcomes. Our search identified 6,615 titles; 61 full texts were included in the final review. Of the 61 included studies, 31 reported both cost and effectiveness outcomes. A total of 41 were set in low- and middle-income countries (LMICs), while 12 were set in high-income countries (HICs); 2 were set in both. Most studies considered isoniazid (INH)-based regimens 6 to 2 months long (n = 45), or longer than 12 months (n = 11). Model parameters and assumptions varied widely between studies. Despite this, all studies found that providing TPT to PLHIV was predicted to be effective at averting TB disease. No TPT regimen was substantially more effective at averting TB disease than any other. The cost of providing TPT and subsequent downstream costs (e.g. post-TPT health systems costs) were estimated to be less than $1,500 (2020 USD) per person in 85% of studies that reported cost outcomes (n = 36), regardless of study setting. All cost-effectiveness analyses concluded that providing TPT to PLHIV was potentially cost-effective compared to not providing TPT. In quantitative analyses, country income classification, consideration of antiretroviral therapy (ART) use, and TPT regimen use significantly impacted cost-effectiveness. Studies evaluating TPT in HICs suggested that TPT may be more effective at preventing TB disease than studies evaluating TPT in LMICs; pooled incremental net monetary benefit, given a willingness-to-pay threshold of country-level per capita gross domestic product (GDP), was $271 in LMICs (95% confidence interval [CI] -$81 to $622, p = 0.12) and was $2,568 in HICs (-$32,115 to $37,251, p = 0.52). Similarly, TPT appeared to be more effective at averting TB disease in HICs; pooled percent reduction in active TB incidence was 20% (13% to 27%, p < 0.001) in LMICs and 37% (-34% to 100%, p = 0.13) in HICs. Key limitations of this review included the heterogeneity of input parameters and assumptions from included studies, which limited pooling of effect estimates, inconsistent reporting of model parameters, which limited sample sizes of quantitative analyses, and database bias toward English publications.

Conclusions

The body of literature related to modeling TPT among PLHIV is large and heterogeneous, making comparisons across studies difficult. Despite this variability, all studies in all settings concluded that providing TPT to PLHIV is potentially effective and cost-effective for preventing TB disease.

SUBMITTER: Uppal A

PROVIDER: S-EPMC8439468 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTuberculosis (TB) preventive therapy (TPT) is an essential component of care for people living with HIV (PLHIV). We compared efficacy, safety, completion, and drug-resistant TB risk for currently recommended TPT regimens through a systematic review and network meta-analysis (NMA) of randomized trials.Methods and findingsWe searched MEDLINE, Embase, and the Cochrane Library from inception through June 9, 2020 for randomized controlled trials (RCTs) comparing 2 or more TPT regimens (or placebo/no treatment) in PLHIV. Two independent reviewers evaluated eligibility, extracted data, and assessed the risk of bias. We grouped TPT strategies as follows: placebo/no treatment, 6 to 12 months of isoniazid, 24 to 72 months of isoniazid, and rifamycin-containing regimens. A frequentist NMA (using graph theory) was carried out for the outcomes of development of TB disease, all-cause mortality, and grade 3 or worse hepatotoxicity. For other outcomes, graphical descriptions or traditional pairwise meta-analyses were carried out as appropriate. The potential role of confounding variables for TB disease and all-cause mortality was assessed through stratified analyses. A total of 6,466 unique studies were screened, and 157 full texts were assessed for eligibility. Of these, 20 studies (reporting 16 randomized trials) were included. The median sample size was 616 (interquartile range [IQR], 317 to 1,892). Eight were conducted in Africa, 3 in Europe, 3 in the Americas, and 2 included sites in multiple continents. According to the NMA, 6 to 12 months of isoniazid were no more efficacious in preventing microbiologically confirmed TB than rifamycin-containing regimens (incidence rate ratio [IRR] 1.0, 95% CI 0.8 to 1.4, p = 0.8); however, 6 to 12 months of isoniazid were associated with a higher incidence of all-cause mortality (IRR 1.6, 95% CI 1.2 to 2.0, p = 0.02) and a higher risk of grade 3 or higher hepatotoxicity (risk difference [RD] 8.9, 95% CI 2.8 to 14.9, p = 0.004). Finally, shorter regimens were associated with higher completion rates relative to longer regimens, and we did not find statistically significant differences in the risk of drug-resistant TB between regimens. Study limitations include potential confounding due to differences in posttreatment follow-up time and TB incidence in the study setting on the estimates of incidence of TB or all-cause mortality, as well as an underrepresentation of pregnant women and children.ConclusionsRifamycin-containing regimens appear safer and at least as effective as isoniazid regimens in preventing TB and death and should be considered part of routine care in PLHIV. Knowledge gaps remain as to which specific rifamycin-containing regimen provides the optimal balance of efficacy, completion, and safety.

Project description: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).

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