Pilot treatment programmes have been successfully conducted in several countries including Côte d'Ivoire, Senegal, Thailand and Uganda, clearly demonstrating that treatment in those settings is feasible, and that adherence to treatment, tolerance of therapy and incidence of resistance are no different from those found in developed countries (20, 28, 29). Expanding care and antiretroviral therapy to all those who need them worldwide raises a number of challenges for sociobehavioural, clinical and operational research. The term "operational research" refers here to an array of subjects and disciplines supporting the design and improvement of the systems that allow effective prevention, treatment, care and, ultimately, vaccines to reach all those who need them. It denotes the sciences underlying the rational organization of care, and might also be called "delivery system research". In its own way, its enquiries tackle problems as difficult and as intellectually challenging as those in the other three areas of research summarized above; the methods are not those of biomedical science, but rather of social science, economics, statistics, engineering, psychology and anthropology, among others.
Operational research, so defined, can help to involve, guide and coordinate the roles of care providers from government, the private sector, nongovernmental organizations, communities, faith-based organizations and the workplace, and to deliver antiretroviral therapy. Equally importantly, such research is needed to measure and monitor in a standardized way the impact of antiretroviral therapy in terms of parameters such as additional years of healthy life, fewer deaths, economic progress across society, development of drug resistance, and adherence to treatment (see Box 5.1).
Key issues to be tackled through operational research include:
- optimizing therapeutic regimens for scaling up therapy, for example by performing clinical trials and following up cohorts of treated patients;
- monitoring tolerance of therapy in trials and open patient cohorts;
- establishing optimal ways of monitoring therapy in the context of resource-limited settings; specifically, improving means of enumerating CD4 cell counts, measuring plasma HIV viral load and assessing viral resistance;
- building surveillance programmes to monitor resistance to antiretroviral drugs: when resistance develops to today's drugs, new treatments will be needed;
- improving diagnosis and treatment of opportunistic infections;
- seeking data on the impact of scaling up antiretroviral therapy on prevention and risky behaviour, mitigation, and stigma and discrimination, and using the data to improve programmes designed to reduce risky behaviours;
- identifying the consequences of antiretroviral treatment scale-up on health systems performance;
- creating peer-to-peer learning systems at the clinic, district and country levels so that new findings discovered in the field, combined with existing knowledge, can be quickly disseminated and applied;
- developing innovative, scalable models of how human resources in resource-poor settings can best be mobilized and trained to tackle HIV/AIDS prevention, care and treatment.
Economic research is essential to ensure that therapeutic strategies using antiretro-virals are successful in developing countries. Earlier cost-effectiveness analyses erroneously concluded that such treatment is not cost effective compared with other interventions, especially prevention. These studies did not adequately consider major issues such as the strong link between treatment and prevention (which are not substitutes but are complementary activities); the economic law of diminishing returns that makes prevention very effective at low levels of coverage but each additional input less effective as coverage approaches 100%; and the underestimation of the impact of HIV/AIDS on economic activity and development. Furthermore, they are now rendered obsolete by the huge fall in the cost of antiretrovirals that has since taken place.
Researchers have already linked the dynamic relationship between potential famine and the spread of HIV among rural agricultural workers; the relationship between HIV and malnutrition in general; and the effect of food insecurity on the autonomy of individuals, particularly women. Understanding the complex intersectoral relationships gives a better picture of HIV's true impact, and illuminates possible points of intervention (30, 31).
To discover and improve methods of scaling up access to treatment, economic analysis must be coupled with clinical data provided by longitudinal follow-up of patients in resource-poor settings. The cost-effectiveness ratio of different clinical and economic strategies will provide information that will help answer questions, such as: at what level can treatment ideally be initiated? What are the most effective strategies for switching regimens? How can biological monitoring be optimized? Economic research will also contribute to the identification and evaluation of different strategies of funding access to treatment. At the macroeconomic level, it will be important to establish how the cost burden is distributed between domestic and international sources and, among domestic contributions, the share and incidence of out-of-pocket payments. At the microeconomic level, the effect of different financing arrangements on treatment adherence, the development of drug resistance, and final treatment outcomes will be significant topics of study.
Health policy analysis
It will be important to identify the factors that affect efforts to increase access to treatment, particularly in the context of health services. Some of the key factors are: leadership and management skills; sufficient and sustained funds for antiretroviral medications; technical competence in drugs and commodities procurement; training; monitoring of outcomes; and, in the public sector, a functioning district health system capable of delivering services. Research should include: identifying which factors increase or hinder integration of HIV/AIDS control programmes with public health policy and collaboration with other programmes; developing policies that support such collaboration and integration; and analysing the roles and comparative advantages of all the stakeholders involved in implementation of HIV/AIDS and other interventions.
Scaling up access to treatment must be used as an opportunity to promote global health reforms at the country level with benefits that go beyond HIV care. There is the potential to create effective incentives to improve health infrastructure in resource-limited settings. Research is needed to identify all the potentially negative and positive externalities of scaling up access and their effects on health systems.
Social inequality in the settings where care is to be implemented, the constraints on resources available for treatment, and the need to define eligibility criteria for the provision of antiretroviral drugs, all call for special attention to the equity dimension of the intervention. Special measures need to be taken in order to avoid the possibility of unwittingly reinforcing existing inequalities, setting up a two-tier system in allocating resources, or weakening other disease control efforts by giving priority to HIV/AIDS. In addition, care must be taken to protect the rights of patients when measures such as partner notification and disclosure are deemed to be necessary, and attention must be directed to the local conditions that may hamper confidentiality, especially when treatment is implemented on a large scale.
Many of the barriers that prevent disadvantaged members of society from accessing health care and obtaining treatment are a result of the deficiencies of health services, and there is a growing awareness that the treatment scale-up initiative represents an opportunity to tackle some of these shortcomings. Hence, it will be necessary regularly to review socioeconomic information about treated patients in order to make sure that poorer people have equal access to medication. More work is needed on the appropriate indicators of equity and how information can be collected about them.
Special consideration should be given to gender as it affects the provision of care. A better understanding is required of the particular circumstances that lead to discrimination against HIV-positive women, and of those conditions that enable women to respond and take control of their own affairs. It would be useful to keep track of programmes that have sought to integrate gender considerations into health services, which have an important role to play.
Another obstacle to care comes from the stigma that is attached to seropositive status, and concerted efforts to assess this information can help define locally effective strategies. There is little doubt that stigma and avoidance of testing and treatment are mutually reinforcing, and that it is precisely the individuals who are marginalized because of their status who are not reached by prevention and care efforts. The evidence base for what works in order to reduce stigma and why is, however, thin and has to be strengthened by well-designed studies, both to substantiate the effect of multiple interventions and to define the packages that are effective in different contexts (32, 33).