Sharonann Lynch, HIV & TB Policy Advisor, Médecins Sans Frontières (MSF) Access Campaign

The first-ever UN high level meeting on tuberculosis (TB) on 26 September 2018 in New York was a crucial political moment for TB. It resulted in an endorsement of the first UN Political Declaration on TB [1], specifying prevention and treatment targets and commitments to mobilizing additional resources for the TB response, including research and development.

However, the meeting was poorly attended by heads of states, even though TB is the number one infectious disease killer of people living with HIV (PLHIV), accounting for nearly a third of the deaths among PLHIV in 2017 (300,0000 of 920,000) [2] [3]. The recent pharmacological innovations notwithstanding, there has not been sufficient dynamism in the tools, operational strategies, and national policies to fight TB in HIV-endemic settings.

If we are to stop the senseless deaths of PLHIV due to TB, then we must urgently address dangerous shortcomings in the areas of TB prevention, diagnosis and treatment adherence, and prioritize programming for populations who are particularly vulnerable to TB. We must introduce innovations, including tools and models of care. Furthermore, we need to increase efforts to close the “know/do gap”, translating research into practice, particularly but not limited to integrating HIV and TB services throughout the continuum of care. We should also be as proactive as possible in providing differentiated interventions that respond to vulnerabilities to TB in specific contexts and populations.

Preventing TB

We must address the gaps in TB/HIV service integration, particularly regarding the lack of provision of TB prophylaxis for PLHIV. While timely scale up of antiretroviral therapy (ART) has helped to radically reduce development of TB disease [4], we need to further minimize this risk by providing TB prophylaxis more systematically upon HIV diagnosis and initiation of ART. In 2017, in the 59 countries that initiated TB preventive therapy (TPT), only 36% of PLHIV had access to TPT [3]. With easier-to-take and more effective drug options available, national HIV programmes in high-burden countries need to prioritize scale-up of TB prophylaxis for PLHIV.

Diagnosing TB

We must improve our ability to promptly and correctly diagnose TB in PLHIV. Approximately half of all TB cases among PLHIV are not diagnosed or treated [2]. This happens for various reasons, including inability to expectorate sputum [5],[6] and using sputum of poor quality with a very low number of bacteria; it could also be that the person may suffer from extra-pulmonary TB, an infection outside of the lungs. In such instances, sputum-based tests are rendered unsuitable [7]. The Determine TB-LAM Ag (TB LAM) test, a rapid urine-based test, is the only TB test shown to reduce mortality [8],[9]. Findings from the STAMP trial suggest that all inpatients living with HIV, regardless of their CD4 cell count, should receive a TB LAM test [10].

The World Health Organization (WHO) goes further, recommending TB LAM for use in outpatient facilities as part of the package of care to address advanced HIV disease [11]. Given that there will be new LAM tests coming to market, it is crucial to soften the ground now by rolling out today’s TB LAM for primary healthcare facilities and offer the test to all PLHIV with TB symptoms who are very ill or have a CD4 cell count below 200.

TB treatment adherence

Innovative approaches from the HIV field show improved adherence if treatment fits into people’s lives rather than the other way round. A way to do this is through people-centred care, which empowers people by providing them with information about their disease, treatment and monitoring and by bringing integrated treatment as close to their homes as possible. While the global health community might be attracted to technological strategies, such as video observed therapy, this ignores the human aspects of the diagnostic and treatment barriers, such as user fees, distance to care and empowering of people affected by HIV and TB.

Vulnerable populations

We need differentiated interventions that respond more robustly to TB vulnerability, including among pregnant women living with HIV, children, adolescents [12] and incarcerated populations. A study in South Africa found that universal TB testing resulted in a 10-fold increase in diagnosing TB among pregnant women living with HIV and reduced early infant mortality [13]. While all countries surveyed in a 2017 report [14] claimed to include active case finding among PLHIV in their national TB programmes, household contact tracing is a low-hanging fruit that is woefully neglected, including for children and adolescents who are particularly vulnerable. While the benefits of HIV testing and HIV self-testing at secondary schools in some high-HIV/TB contexts has been studied, we should also be looking at the impact of routine TB testing.

The HIV and TB communities do not pay sufficient attention to incarcerated populations and the need for scale-up of a standardized package of HIV and TB treatment and prophylaxis. WHO, as well as national ministries of health and justice, should step up to the challenge of ensuring that prisons are not a crucible of infectious diseases and should regularly report on progress or the lack thereof.

Rather than a conservative one-size-fits-all approach, we need protocol guidelines and operational guidance specific to high-HIV/TB burden settings. Earlier on in the HIV/TB response, smarter segmentation and specification given epidemiological profiles and main drivers of mortality could have reduced TB deaths and TB incidence, such as rolling out ‘test and start’ of ART. Since we do not have a time machine, we need to ask ourselves the question today: where else are we needlessly delaying or missing opportunities that are specific to TB vulnerabilities?

References:

[1] UNGA. Political declaration of the high-level meeting of the General Assembly on the fight against tuberculosis. (Document A/73/L.4). Endorsed by UNGA on 10 October 2018. Available from: https://www.un.org/en/ga/73/resolutions.shtml.

[2] WHO. HIV-Associated tuberculosis factsheet. 2018. Available from: https://www.who.int/tb/areas-of-work/tb-hiv/tbhiv_factsheet.pdf?ua=1.

[3] WHO. Global tuberculosis report 2018. 2018. Available from: http://apps.who.int/iris/bitstream/handle/10665/274453/9789241565646-eng.pdf?ua=1.

[4] Williams, Brian G., et al. Antiretroviral therapy for tuberculosis control in nine African countries. Proceedings of the National Academy of Sciences 107.45 (2010): 19485-19489. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2984151/.

[5] Peter, Jonathan G., et al. Diagnostic accuracy of a urine LAM strip-test for TB detection in HIV-infected hospitalised patients. European respiratory journal (2012): erj02017-2011. Available from: https://erj.ersjournals.com/content/40/5/1211.long.

[6] Gonzalez-Angulo, Y., et al. Sputum induction for the diagnosis of pulmonary tuberculosis: a systematic review and meta-analysis. European journal of clinical microbiology & infectious diseases 31.7 (2012): 1619-1630. Available from: https://link.springer.com/article/10.1007%2Fs10096-011-1485-6.

[7] WHO. The use of lateral flow urine lipoarabinomannan assay (LF-LAM) for the diagnosis and screening of active tuberculosis in people with HIV. Policy Guidance. 2015. Available from: http://www.who.int/tb/areas-of-work/laboratory/policy_statement_lam_web.pdf.

[8] Gupta-Wright, Ankur, et al. Detection of lipoarabinomannan (LAM) in urine is an independent predictor of mortality risk in patients receiving treatment for HIV-associated tuberculosis in sub-Saharan Africa: a systematic review and meta-analysis. BMC medicine 14.1 (2016): 53. Available from: https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-016-0603-9.  

[9] Peter, Jonny G., et al. Effect on mortality of point-of-care, urine-based lipoarabinomannan testing to guide tuberculosis treatment initiation in HIV-positive hospital inpatients: a pragmatic, parallel-group, multicountry, open-label, randomised controlled trial. The Lancet 387.10024 (2016): 1187-1197. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26970721.

[10] Gupta-Wright, Ankur, et al. Rapid urine-based screening for tuberculosis in HIV-positive patients admitted to hospital in Africa (STAMP): a pragmatic, multicentre, parallel-group, double-blind, randomised controlled trial. The Lancet 392.10144 (2018): 292-301. Available from: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31267-4/fulltext.

[11] WHO. Guidelines for managing advanced HIV disease and rapid initiation of antiretroviral therapy, July 2017. (2017). Available from: https://apps.who.int/iris/bitstream/handle/10665/255884/9789241550062-eng.pdf.

[12] Wood, Robin, et al. Changing prevalence of tuberculosis infection with increasing age in high-burden townships in South Africa. The international journal of tuberculosis and lung disease 14.4 (2010): 406-412. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837545/.

[13] Martinson, Neil, et al. Universal sputum testing vs symptom-based testing for tuberculosis (TB) in HIV infected pregnant women: a cluster-randomised implementation trial in South Africa. 9th IAS Conference on HIV Science. 23–26 July 2017. Paris. Poster abstract TUPDB0204LB. 2017. Available from: http://programme.ias2017.org/Abstract/Abstract/5746.

[14] MSF and Stop TB Partnership. Out of Step 2017. TB policies in 29 countries. A survey of prevention, testing and treatment policies and practices. July 2017. Available from: http://www.stoptb.org/assets/documents/outofstep/UNOPS_out_of_step_2017_55_online.pdf.