Towards tuberculosis elimination: reaching the most at-risk populations with tuberculosis preventive therapy

In The Lancet Global Health, Gabriel Chamie and colleagues1Chamie G Hahn JA Kekibiina A et al.Financial incentives for reduced alcohol use and increased isoniazid adherence during tuberculosis preventive therapy among people with HIV in Uganda: an open-label, factorial randomised controlled trial.Lancet Glob Health. 2023; 11: e1899-e1910Google Scholar demonstrate the positive effect of financial incentives on reinforcing short-term alcohol abstinence among people living with HIV receiving tuberculosis preventive therapy in Uganda. Sub-Saharan Africa has a substantial burden of alcohol use disorder (AUD), defined as harmful, hazardous, or dependent alcohol use. A recent systematic review showed that the average 1-year prevalence of AUD among people with HIV was 22·03% (95% CI 17·18–28·67).2Necho M Belete A Getachew Y The prevalence and factors associated with alcohol use disorder among people living with HIV/AIDS in Africa: a systematic review and meta-analysis.Subst Abuse Treat Prev Policy. 2020; 15: 63Crossref Scopus (21) Google Scholar In addition, tuberculosis is still the leading cause of morbidity and mortality among people with HIV in sub-Saharan Africa despite increasing antiretroviral coverage across most of the region.3Letang E Ellis J Naidoo K et al.Tuberculosis–HIV co-infection: progress and challenges after two decades of global antiretroviral treatment roll-out.Arch Bronconeumol. 2020; 56: 446-454Crossref Google Scholar Furthermore, AUD independently increases the risk of progression of latent tuberculosis to active tuberculosis.4Rehm J Samokhvalov AV Neuman MG et al.The association between alcohol use, alcohol use disorders and tuberculosis (TB). A systematic review.BMC Public Health. 2009; 9: 450Crossref PubMed Scopus (284) Google Scholar Finally, overlapping risk factors for AUD and tuberculosis (eg, being male and using tobacco2Necho M Belete A Getachew Y The prevalence and factors associated with alcohol use disorder among people living with HIV/AIDS in Africa: a systematic review and meta-analysis.Subst Abuse Treat Prev Policy. 2020; 15: 63Crossref Scopus (21) Google Scholar) mean that these three ailments—HIV, AUD, and tuberculosis—are likely to affect the same individuals. Provision of tuberculosis preventive therapy to people with HIV who have AUD should therefore be a priority intervention for tuberculosis control programmes in this region. However, due to concerns about hepatotoxicity, particularly in routine care settings which have limited capacity to monitor liver function before and during tuberculosis preventive therapy, these patients (those with AUD) are excluded from receiving tuberculosis preventive therapy in Uganda.5Uganda Ministry of HealthIsoniazid preventive therapy in Uganda: a health worker's guide. Republic of Uganda, Ministry of Health, Kampala2014Google Scholar Chamie and colleagues have shown that the use of financial incentives can result in reduced alcohol intake, making it safer for patients with AUD to receive tuberculosis preventive therapy. The use of financial incentives to achieve favourable health outcomes is not uncommon in low-income and middle-income countries. Financial incentives have been shown to be efficacious in trials to encourage people with HIV to achieve and maintain viral load suppression,6Fahey CA Njau PF Katabaro E et al.Financial incentives to promote retention in care and viral suppression in adults with HIV initiating antiretroviral therapy in Tanzania: a three-arm randomised controlled trial.Lancet HIV. 2020; 7: e762-e771Summary Full Text Full Text PDF Scopus (0) Google Scholar improve treatment completion among patients with multidrug resistant tuberculosis,7Baral SC Aryal Y Bhattrai R King R Newell JN The importance of providing counselling and financial support to patients receiving treatment for multi-drug resistant TB: mixed method qualitative and pilot intervention studies.BMC Public Health. 2014; 14: 46Crossref PubMed Scopus (62) Google Scholar and encourage household contacts to initiate tuberculosis preventive therapy.8Wingfield T Tovar MA Huff D et al.Socioeconomic support to improve initiation of tuberculosis preventive therapy and increase tuberculosis treatment success in Peru: a household-randomised, controlled evaluation.Lancet. 2017; 389: S16Summary Full Text Full Text PDF PubMed Google Scholar The increased use of digital financial services across sub-Saharan Africa through phone-based mobile money services means that these interventions are easier to scale and to monitor even in remote areas. In addition, Chamie and colleagues used a schedule of financial incentives that is affordable for most low-income and middle-income countries and is similar to incentives used in previous studies within the region.6Fahey CA Njau PF Katabaro E et al.Financial incentives to promote retention in care and viral suppression in adults with HIV initiating antiretroviral therapy in Tanzania: a three-arm randomised controlled trial.Lancet HIV. 2020; 7: e762-e771Summary Full Text Full Text PDF Scopus (0) Google Scholar An interesting part of this study is that the incidence of hepatotoxicity was low (overall, 7% had hepatotoxicity resulting in isoniazid discontinuation) and similar to that observed in routine care settings in Uganda. This evidence indicates that strengthening of clinical monitoring to improve eligibility criteria (the study excluded individuals with baseline elevated liver enzymes) could enable health-care settings to offer tuberculosis preventive therapy to a higher number of individuals with HIV who have AUD. However, a notable limitation of this study is that the tuberculosis preventive therapy regimen used (6 months of daily isoniazid [6H]) has largely been replaced by a shorter regimen consisting of 12 weekly doses of rifampicin and isoniazid (3HP). 3HP has similar efficacy to 6H but has higher treatment completion rates and significantly lower risk of hepatotoxicity.9Hamada Y Ford N Schenkel K Getahun H Three-month weekly rifapentine plus isoniazid for tuberculosis preventive treatment: a systematic review.Int J Tuberc Lung Dis. 2018; 22: 1422-1428Crossref PubMed Scopus (26) Google Scholar Larger scale adaptation of this intervention might therefore require modification of trial components. Another interesting aspect of this study is the possibility that it brings for the integration of financial incentives into the management of substance use disorders in Uganda. Although multifaceted interventions that include financial incentives have been used for the management of substance use disorders with considerable success in developed countries,10Volpp KG Troxel AB Pauly M V et al.A randomized, controlled trial of financial incentives for smoking cessation.N Engl J Med. 2009; 360: 699-709Crossref PubMed Scopus (613) Google Scholar they have not been widely deployed in Uganda. This might be partly due to concerns about the sustainability of such interventions in our setting. However, given their demonstrated success, the use of financial incentives, even if only for initial intensive phases of substance use management, should be considered in this setting. Perhaps the most important aspect of this study is that it evaluates an intervention that can enable equitable provision of tuberculosis preventive therapy to a population that is most at risk for morbidity and mortality from tuberculosis. Only by reaching such populations can country programmes hope to meet the current global targets for provision of tuberculosis preventive therapy. I declare no competing interests. Financial incentives for reduced alcohol use and increased isoniazid adherence during tuberculosis preventive therapy among people with HIV in Uganda: an open-label, factorial randomised controlled trialEscalating financial incentives contingent on recent alcohol abstinence led to significantly lower biomarker-confirmed alcohol use versus control, but incentives for recent isoniazid adherence did not lead to changes in adherence. The alcohol intervention was efficacious despite less intensive frequency of incentives and clinic visits than traditional programmes for substance use, suggesting that pragmatic modifications of contingency management for resource-limited settings can have efficacy and that further evaluation of implementation is merited. Full-Text PDF Open Access