Using mathematical modelling to optimise TB control in high-HIV prevalence settings
The TB Modelling and Analysis Consortium (www.tb-mac.org), was launched in 2012 in order to coordinate modelling with TB research activities. A symposium on Saturday morning at the 44th Union World Conference on Lung Health was dedicated to explaining the value of modelling to help guide strategic decision-making and the work of TB-MAC thus far.
Mathematical modelling can help explain epidemics (how they evolve and are driven or sustained) and also the potential impact that interventions may have on them. Critically, as Dr Michael Kimerling, of the Bill and Melinda Gates Foundation explained, “modelling and analysis is needed for [policy] decision making and to evaluate investment trade-offs.”
There had been many individual modelling efforts going on concurrently including what the Gates Foundation has been doing to guide investments in its product development partners, FIND, TB Alliance, Aeras; as well as efforts by academics, the NIH’s Diagnostics Forum, WHO’s Global TB Programme, the Stop TB Partnership to make decisions about TB targets and the upcoming Global Plan, by the private sector and country delivery programmes, and by the Global Fund to improve efficiency and effectiveness.
TB-MAC seeks to align these efforts to find ways to accelerate development and delivery of innovations. It’s objectives included identifying research questions where modelling or other quantitative research might prove useful, share data, information and expertise to assist in TB control decision making, fund small modelling/analysis projects, and then to disseminate results and tools to stakeholders such as TB programmes and donors.
Its first activities have focused on optimising TB control in high-HIV prevalence settings. It is also engaged in work on the impact and cost-effectiveness of current and future diagnostics for TB, the rational introduction of new drugs and regimens, and the post-2015 TB control targets.
Dr Kimerling noted that the www.tb-mac.org website also provides up to date information, meetings reports, and systematic reviews (on all the mathematical and economic TB modelling, TB-HIV and diagnostics).
Dr Rein Houben explained some of the benefits of modelling in more detail. For instance, modelling can explore the potential impact of combined interventions on the epidemic (some interventions may not only be complementary but have a synergistic impact on the epidemic). Or modelling could project the impacts (on the epidemic or on the cost) of a gradual introduction versus more accelerated scale-up of an innovation or intervention.
But there are also many challenges modelling the TB epidemic — for instance, for some research questions, Houben said, “Empirical data are very scarce, but answers are still needed to inform policy decisions.”
Dr Houben reported on the first meeting of TB-MAC, bringing together empirical scientists, policy makers and mathematical modellers, held in Johannesburg, September 2012. An output of the meeting was the TB-HIV modelling research agenda (the full report on that meeting is available on the TB-MAC website: www.tb-mac.org/WorkAreas/WorkArea/1
5 main research areas:
- The difficult diagnosis and high mortality of TB/HIV
- The high risk of disease progression
- Health systems issues
- Uncertainty in TB/HIV natural history
- The likely interaction between combined interventions for HIV-associated TB.
Other speakers at the symposium described several of the recent key modelling research projects activities.
Carel Pretorius gave a presentation on TIME – a country-level modelling tool for TB and HIV. Essentially, this has involved a collaborative effort to expand an existing suite of policy tools (the Spectrum suite) — which is widely used to support country-level planning for public health programmes e.g. MCH, HIV, Child Survival, Family planning and so on — to include TB. The spectrum suite helps develop estimates of disease and health burden, resource needs and facilitates integration across programme areas.
Several partners including the Futures Institute, TB-MAC, the Global TB Programme/WHO, UNAIDS, and the STOP TB Partnership have been working together on the TIME tool, making sure that it fits to past national epidemics and accesses the current data, and understanding of TB transmission dynamics and natural history.
Programmes using it should be able to better project epidemic trends into the future, and explore cost and impact of interventions (such as increased case detection, increased treatment success rates, IPT for people living with HIV, improved MDR diagnosis and treatment, ART expansion and other HIV interventions. The modelling should help countries prioritise activities and allocate sufficient resources.
TIME will get its trial run in an upcoming project in Sudan later this year where the partners hope to steer the county towards development of an evidence-based TB strategic plan, with support from the Global Fund. It is then hoped that the team can build upon that experience in other countries shortly afterwards.
Tom Sumner presented an analysis of the data from the recent major studies of isoniazid preventive therapy (IPT) in HIV-infected individuals in high-burden settings, which concluded that even with relatively high rates of TB reinfection, the only explanation for the short duration of IPT’s effect in these trials is that isoniazid does not cure latent TB in people living with HIV. Therefore, a better TB preventive regimen is needed — although, he added, in settings with high rates of reinfection, people living with HIV may still need to remain on preventive therapy for life [Ed’s note: or, perhaps, they may need to take curative preventive courses every year or so recurrently — and the frequency may depend upon whether they are on effective ART].
Gwenan Knight: The potential impact and cost-effectiveness of ‘theoretical’ new TB vaccines. While everyone wants a vaccine that could be given to infants early in life, her modelling shows that a vaccine given to adults could actually have the greatest impact on the TB epidemic.
Anna Vassall reported on efforts to model the economics of introducing Xpert MTB/RIF for TB control in HIV-prevalent settings. This is a case where modelling actually affected decision making — as it provided support for South Africa’s progressive decision to scale up and switch over to Xpert MTB/RIF as its first-line TB diagnostic tool.
[TreatmentScienceWriters may cover symposium in more detail in an upcoming report].
Still to come from Saturday:
- New data on the initiation of antiretroviral treatment in people living with HIV on TB treatment (that supports WHO’s Global TB Programme recommendations to start as soon as possible within two to eight weeks of going on TB treatment) but that add clinical nuance that might increase the chances of success in these patients. For instance, one study very clearly showed that adherence to TB treatment goes down when people start ART — probably because of pill burden — so these patients may benefit from more intensive adherence support. At the same time, another studies suggested an immunological basis for the improved long term survival of associated with early treatment with ART in TB patients with advanced HIV
- A report of high rates of morbidity and mortality from undetected TB in people living with advanced HIV and an analysis of whether it might be best to put all people living with HIV who present to clinics with low CD4 cell counts on TB treatment
- The TB-HIV late-breakers including:
- Data on the successful implementation of methadone as an essential component of TB treatment success for people who use heroin in Tanzania, and
- ‘Should urine be the new port of call for TB diagnostics’ [those are Dr Steve Lawn’s words, not our own]