These data can be used by economists to estimate the likely costs of UTT interventions in a range of settings with different input prices. Data on estimated costs can be integrated with the mathematical models to obtain estimates of cost-effectiveness under different conditions, which may be expressed for example as cost per HIV infection averted or cost per disability-adjusted life year DALY.
These estimates will be based on differences in projected numbers of HIV infections over a defined study period for example 10 or 15 years for the proposed UTT intervention and the current level of diagnosis and treatment, combined with data on differences in costs under the two scenarios. When computing costs, it is important that account is taken not only of the direct costs of implementing the UTT intervention but also of costs averted due to future reductions in HIV infections needing care and other services as well as reductions in HIV-related morbidity due to earlier treatment and higher uptake of treatment.
Previous modelling work suggests that the saving of hospital and other health-care costs for these illnesses will largely offset the costs of implementing UTT at least in a South African setting [ 12 , 21 , ].
It may also be helpful to model the cost-effectiveness of UTT compared with that of a more limited intervention aimed at expanding testing and increasing the numbers of patients treated promptly according to current treatment guidelines.
While modelling should provide useful projections of cost-effectiveness under a range of conditions, there will always be uncertainties about the validity of such projections given the large number of assumptions required, many not well supported by empirical evidence.
UTT represents a controversial and logistically very challenging intervention, with a range of possible adverse effects, ranging from increased stigma and behavioural disinhibition to increases in drug resistance and over-burdening of health services.
A decision to go ahead with wide-scale implementation is likely to depend on proof of concept obtained through one or more rigorously conducted cluster-randomised trials. Such trials could directly collect data on population-level impact on HIV incidence as well as on implementation costs and many other outcomes including the potential adverse effects noted above. In this section, we briefly discuss key design aspects of such a trial, which is likely to involve random allocation of a number of study communities to the UTT intervention or a standard of care control arm, and follow-up over several years to record effects on HIV incidence at population level.
RCTs remain the gold standard for the evaluation of health interventions, where they are feasible. Cluster randomisation is called for where the intervention has by its nature to be implemented at population level, as is the case for UTT.
By comparison of both effects and costs between intervention and control clusters, a CRT can provide rigorous empirical estimates of effectiveness and cost-effectiveness to guide the decisions of policy-makers regarding the implementation of health interventions. First, a multi-country study will help to ensure that the results of the trial are generalisable and reflect the performance of the strategy under a range of conditions. Second, the size of such a trial and the large number of clusters required are likely to call for a multi-country study.
It is likely that the effects of the intervention will show some variation due to differences in the existing coverage of testing and treatment services, variations in the uptake and delivery of the UTT strategy, underlying differences in the epidemiology and transmission dynamics of HIV and other contextual factors.
It is important to note that the proposed CRT will be powered to determine the overall effect of UTT, averaged over sites. While the data may give some indication of relative effects of UTT in different settings, the study will not be powered to provide precise data on variations in effectiveness between countries.
Once again, there will be a role for mathematical modelling in taking the empirical data from the CRT and using them to provide refined estimates of effectiveness and cost-effectiveness in different settings. The choice of clusters is likely to depend on the level at which the intervention is implemented, as well as the transmission dynamics of HIV infection.
Ideally, to correctly capture the indirect effects of the intervention and to avoid contamination due to sexual contacts with individuals from outside the cluster, the cluster would be large enough to ensure that most sexual contacts occur within the cluster.
However, the requirement for a relatively large number of clusters and the need to constrain costs will necessitate a compromise between feasibility and validity. In practice, the cluster might be defined as the catchment population of a health facility through which the UTT intervention is to be delivered and coordinated. To minimise contamination, and problems due to overlapping catchments of different health facilities, it may be preferable to select widely dispersed rural communities or small towns, rather than areas within large urban conurbations.
A critical component of the CRT design is comparison of effects in intervention clusters with comparable clusters in a control arm. To maximise study power and to provide the most relevant evidence for health policy, it would arguably be desirable for the control arm to receive the current level of service provision in the study community with no additional interventions. However, the ethical acceptability of enrolling and following up study communities where currently recommended criteria for service provision are not adhered to, as is likely to be the case in many resource-poor settings, would need to be carefully considered.
International guidelines on this issue have been an area of intense debate and disagreement, and are under constant review. Responsibilities to trial participants have to be balanced against the urgent need for valid data to guide national and international policy, as well as concerns over providing enhanced service levels which are unlikely to be sustained after the end of a study. This would certainly result in higher ART coverage than at present, thus diluting any difference in outcomes between the study arms, and this would need to be allowed for in sample size calculations.
An alternative is to provide communities in the control arm with some other intervention, unrelated to HIV infection, that would be of intrinsic value to the community. It is likely that random samples of adults from the study communities will be followed up to measure effects on HIV incidence.
Enrolling individuals to a research cohort of this kind may impose additional constraints regarding the responsibilities of the research team. What access would this cohort have to HIV counselling, testing and treatment? Would there be an expectation that proven HIV prevention methods such as male circumcision should be made available to these cohorts? These are difficult questions that would require careful consideration and discussion with national authorities and ethical review committees.
It is likely that the UTT strategy will take several years to show its full effect for two main reasons. First, it will take some time to introduce the intervention into the study communities and to expand coverage so that a maximal proportion of the population have been tested and a high proportion of those diagnosed HIV-positive have been started on ART.
Similarly, it may also take some time for potential adverse effects of the intervention, such as HIV-related stigma or behavioural disinhibition, to be observable.
Conversely, some initial problems with the intervention may be resolved over time; for example, it may take time to establish the trust of the community in the confidentiality and quality of the services, and uptake may increase substantially once this has been achieved.
Previous mathematical modelling showed that UTT would have an immediate effect on HIV incidence but that effects would accumulate over time. For these reasons, a CRT would require a long enough follow-up period so that at least the early effects of the intervention are detectable, and this is likely to be at least two to three years. The primary objective of a CRT would be to measure the impact of the UTT intervention on HIV incidence at population level, and so HIV infection in the general population of the study communities would be the primary endpoint.
If a reliable assay that can detect recent HIV infection is available and validated, then HIV incidence could be measured through a cross-sectional survey of a random sample of the population at the end of the follow-up period. Unfortunately, none of the existing assays have been validated in the likely study populations for a CRT, where HIV subtypes differ from those that predominate in settings where most of these assays have been developed.
If such assays are not available, measurement of HIV incidence is likely to require enrolment and follow-up of a cohort which might be a random sample of the adult population. There are likely to be numerous secondary endpoints and these are likely to include HIV-related morbidity and mortality; uptake of testing; uptake of treatment; adherence and treatment failure; drug resistance and toxicity; HIV-related stigma; TB incidence; HIV vertical transmission; and behavioural disinhibition. Special methods are required for sample size determination for a CRT [ ].
These depend on the expected incidence of HIV; the effect size on which the study is to be powered; and the between-cluster coefficient of variation in the primary endpoint. Both the number of clusters per study arm and the number of individuals to be followed up in each cluster need to be specified. Note that the latter may be a random sample of the community, and it is not necessary to follow up the entire population of each community.
In this paper, we have reviewed the research questions that need to be addressed to provide the evidence needed to inform policy on the implementation of the UTT strategy, and outlined possible research methods that could be used to answer these. Some of these studies can be done using existing data, but new field research will also be needed. In particular, we propose a phased sequence of studies, commencing with pilot studies looking at the feasibility and acceptability of the intervention.
If these show favourable results, it might then be appropriate to proceed to a full-scale CRT to measure the impact of the intervention on HIV incidence at population level, as well as a wide range of secondary outcomes. Such a trial would produce rigorous evidence on the beneficial and adverse effects of the UTT intervention which, together with cost data, would provide estimates of cost-effectiveness to guide policy decisions on the potential wide-scale implementation of the intervention.
One of the key limitations of the proposed CRT is that it is unlikely to be feasible to follow up the study communities for more than a few years, whereas model projections show that the full impact of such an approach may not be seen for 15 to 20 years.
However, these projections do predict a substantial early effect of the intervention, and observations confirming such an effect would provide strong support for wider introduction.
Mathematical models could be fitted to data from a CRT on early effects of UTT and used to refine estimates of longer-term impact. In any case, the need for more effective prevention strategies is urgent, and cannot wait for the results of a trial extending for 10 years or more. It is by no means certain that initial feasibility studies will show the UTT approach to be feasible or acceptable in resource-poor settings. We suggest that work should continue on such approaches in parallel to the proposed initial studies of UTT.
There is increasing recognition that single interventions are unlikely to be sufficient to bring the HIV epidemic under effective control in the most severely affected countries, and that a combination of partially effective methods will be required [ ].
UTT itself represents a combination prevention tool as it involves a combination of testing, linkage to care and early treatment. Achieving high uptake of testing through a UTT programme provides an opportunity to offer other proven interventions such as male circumcision, condoms and potentially microbicides or oral PrEP.
The CRT design discussed above could be extended to measure the population-level impact of a combination prevention package that includes UTT combined with other interventions. Whether or not the research studies outlined in this paper show that UTT is a feasible and effective HIV prevention intervention, they will provide a wide range of data that will be of value in guiding the strengthening of services for testing and treatment in sub-Saharan Africa - for both individual and public health benefit.
We are grateful to Debby Watson-Jones for her helpful comments on a draft version of this paper. We thank the reviewer from Current HIV Research for the helpful comments before finalisation of this paper. HIVinfected adults. Daily oral antiretroviral use for the prevention of HIV infection in heterosexually active young adults in Botswana: results from the TDF2 study.
National Center for Biotechnology Information , U. Current HIV Research. Bentham Science Publishers. Curr HIV Res. Published online Sep. Author information Article notes Copyright and License information Disclaimer. This article has been cited by other articles in PMC. Abstract Achieving high coverage of antiretroviral treatment ART in resource-poor settings will become increasingly difficult unless HIV incidence can be reduced substantially.
Table 1. Who should deliver VCT? What is the added role of self-testing? What is the role of expanded PIT in medical settings? What modes of promotion are most effective in achieving uptake of testing? What aspects of service provision ameliorate identified barriers? What factors are associated with non-uptake and failure to re-test? Open in a separate window. Models of Service Provision The most suitable model of service provision may vary depending on the context and setting where UTT is to be implemented.
Frequency of Testing Information is needed on the frequency of testing that should be recommended for a UTT programme. Counselling Strategies Existing models of counselling prior to an HIV test are generally not evidence-based [ 61 ] and there have been doubts as to whether pre-test counselling confers any benefit [ 62 ].
Uptake of Testing Against the current backdrop of inadequate coverage and uptake, universal HIV testing is an ambitious goal. Costs Cost-effectiveness studies of the various methods that may be piloted hold the key to identifying which strategies will be feasible for ministries of health and other providers who have to find sustainable ways to provide services with limited resources.
Table 2. What factors act as barriers to uptake of treatment after testing positive? Where should treatment be provided? Who should deliver these treatment services?
Models of Treatment Provision Different approaches to treatment provision may be needed in different settings, and operational research and pilot studies will be needed to assess their feasibility and effectiveness.
Home-based care: Whether or not VCT is provided through a door-to-door campaign, it may be possible to offer treatment and follow-up through a continuous system of home-based care.
Facility-based provision: This is the standard approach at present but could be adapted to offer extended access to ART by increasing staff, clinic space or opening hours. Community treatment centres: If existing health facilities are not close enough to local communities, consideration could be given to establishing community-based treatment centres.
Work-place provision: This would probably be most appropriate at sites where there is a large workforce employed in a particular occupation, such as mines or plantations. Choice of Treatment Regimens The choice of a safe, effective and acceptable first-line ART regimen that can be used irrespective of CD4 count in a UTT programme is critical in order to limit the potential development of drug resistance, drug-related toxicities and poor adherence.
Approaches to Monitoring and Follow-Up Routine inclusion of laboratory-based testing involves additional logistical, resource and staff constraints, potentially undermining the feasibility of delivering an effective UTT programme. Adherence to ART The risk of developing viral resistance to ART is directly linked to adherence to therapy [ 97 ] and drug choice, with enhanced viral suppression conferred by boosted protease inhibitor- or non-nucleoside reverse transcriptase inhibitor-containing regimens compared with triple nucleoside reverse transcriptase inhibitor combinations [ 98 ].
Uptake of Treatment Uptake of immediate ART can be expected to vary in different settings [ 69 , ] and feasibility studies are needed to measure the actual uptake achieved by different UTT approaches in different areas in sub-Saharan Africa.
Outcome of Treatment Feasibility studies of UTT programmes will also need to collect detailed data on the outcomes of treatment. Effects of UTT on Health Services There are concerns that substantial increases in numbers of patients on ART could lead to over-burdening of poorly-resourced and understaffed health facilities, leading to adverse effects on health services.
Costs Policy decisions on implementation of the UTT strategy will depend critically on reliable cost-effectiveness estimates, particularly since initial costs of UTT roll-out may be very high.
Table 3. Is delivery of UTT associated with behavioural disinhibition? Standard of Care in Control Arm A critical component of the CRT design is comparison of effects in intervention clusters with comparable clusters in a control arm. Duration of Follow-Up It is likely that the UTT strategy will take several years to show its full effect for two main reasons. Table 4. WHO Progress Report.
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Support Center Support Center. It should also involve a feedback loop to the planners of the next evaluation and a built-in feedback mechanism so that past lessons can effectively inform new efforts.
These stages represent merely the outline for developing a sound evaluation strategy. Additional resources should be referred to at the start of a new evaluation. Although programme evaluation requires some expertise, what is most important are programme management, staff and key stakeholders who are interested in examining and continuously working to meet their programme's objectives.
Evaluation of a specific aspect of programme implementation can take the form of operational research, which is any research designed to improve the performance of programmes and policies.
During the operational research, a problem with service delivery may be identified and a solution or several approaches to adjusting the programme developed. These solutions are implemented and any changes in the expected outputs or outcomes of service delivery resulting from the adjustments are measured. Each country may decide the specific focus of evaluation based on its strategy, key areas of weakness identified through routine monitoring and resource availability.
Some common topics for evaluation include:. What is the comparable cost efficiency of different modes of service delivery with respect to case-finding? Or covering high-priority populations? What have been the key bottlenecks to scaling up service utilization? Or scaling up PITC in different settings?
All rights reserved. Turn recording back on. National Center for Biotechnology Information , U. Show details Geneva: World Health Organization ; Search term. Process steps for evaluation Ideally, evaluation activities are planned at the beginning of a new intervention e. The basic process of evaluation should involve a few key steps: Step1. Step 2. Step 3. Step 4. Step 5. Step 6. Role of operational research in monitoring and evaluation Evaluation of a specific aspect of programme implementation can take the form of operational research, which is any research designed to improve the performance of programmes and policies.
Potential topics for evaluation Each country may decide the specific focus of evaluation based on its strategy, key areas of weakness identified through routine monitoring and resource availability.
Some common topics for evaluation include: Outcome evaluation Is the scale and distribution of services commensurate with the need of the epidemic? Are there disparities among different groups with respect to the proportion of people who are diagnosed as positive and access early treatment and care?
In this Page. Process steps for evaluation Role of operational research in monitoring and evaluation Potential topics for evaluation. Other titles in this collection. Recent Activity.
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