and appropriately addressed. More broadly, in light of the larger social, cultural, environmental, and economic context of the HIV/AIDS pandemic, how can the research agenda be expanded such that the upstream determinants of infectious disease emergence, including poverty, are addressed in a meaningful and adequate way? Can poverty-reduction programs and ART programs be coordinated so as to be complementary and synergistic? Other cultural dimensions must also be considered. For example, in South Africa the majority of HIV-infected people use traditional medicines. Thus the consequences and effectiveness of using these treatments (as well as other non-ARV immune regulators) need to be objectively examined to better inform those prescribing ARVs about how to treat these patients.

It must be recognized that HIV/AIDS is not just a medical problem. Rather, to address the problem it is necessary to examine the total system—with its many complex negative and positive feedbacks—from a systems perspective. The question arises, however, of how this framework can and should be applied to research in the field. What are the practical implications of this type of thinking for budgeting for operations research to support ART scale-up?

Finally, the importance of modeling cost-effectiveness considerations and incorporating them into operations research questions should be neither underestimated nor overestimated. Models that can be used to predict demand for drugs and other resource requirements need to be developed and validated so that planners can ensure continuity of drugs and care in the face of changing needs. Regardless of how important the immediate health outcomes of any intervention or practice may be, the more cost-effective a process is, the more people will benefit. For example, although the expensive state-of-the-art laboratory monitoring standards applied in the United States may minimize treatment failure, reliance on such standards in resource-limited settings would also minimize the number of people who could receive treatment. Thus it is important to consider cost-effective-ness in addition to clinical outcomes when testing various treatment or other ARV-related interventions.


The WHO guidelines provide an excellent, evidence-based set of criteria for determining when to initiate therapy, how to monitor therapy, when to change drugs or regimens, how to incorporate care and treatment for opportunistic infections into ART, and so on. Nonetheless, the recommendations are intended to serve only as a starting point for the development of national guidelines. Some of the WHO guidelines are necessarily vague because of incomplete clinical knowledge. An example is the recommended treatment for women of childbearing potential or those who are pregnant.

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