In 2001, the number of people living with HIV/AIDS worldwide was 40 million, with more than 95% living in the developing world.

Threatening the very roots of countries
The HIV/AIDS pandemic in Sub-Saharan Africa has quickly evolved from a major health issue to a complex international emergency that undermines the social and economic fabric of nations and reverses decades of development.
In contrast, the epidemic in the Asia-Pacific region is in its early stages. In many respects, the HIV epidemic in India currently is where the epidemic in South Africa was 5 or 10 years ago. It is feared that the pandemic in Southeast Asia may increase at a similar exponential rate if there are no appropriate interventions.

The need for antiretroviral therapy
Although prevention programmes are necessary, those alone will not suffice to check the spread of HIV. Efforts at developing an effective vaccine or a vaginal microbicide have been slow.
As prevention alone cannot control the epidemic, and because no magic bullet is on the horizon, treatment is considered imperative. In countries that have used antiretroviral therapy, morbidity and mortality have been reduced. Further benefits include slower progression of the epidemic, reduced future health care expenditure, fewer orphans, more sustained economic productivity from a healthier workforce, and greater social and political stability. In fact, prevention and treatment are now perceived as two sides of the same coin. Effective treatment is likely to decrease the rate of transmission and curb the spread of the epidemic.

Obstacles to using antiretroviral therapy (ART) in developing countries
Although the arguments for widespread use of antiretroviral therapy are compelling, many factors have limited its use in resource-poor settings. Access and availability are part of the problem. Other contributing factors include the high cost of tests used for diagnosis and monitoring, lack of infrastructure and expertise, and the presence of other pressing health care concerns like malaria and TB. In some parts of the developing world, many do not have access even to food and clean water.
Yet another difficulty lies in the complexity of antiretroviral therapy. Antiretroviral drugs can have numerous toxicities. Patient adherence is critical to treatment success but is very difficult to achieve.


New approaches for tackling the problem
It may not seem possible to immediately translate the sophisticated, individualized methods of HIV care employed in the developed world to resource-poor nations. However, the objective of providing treatment is to relieve the suffering of millions and to prevent a social, economic and demographic catastrophe. In pursuit of this goal, treatment approaches being practiced in the west may be slightly modified, with the basic standard of care remaining full and durable suppression of HIV replication.
Even though HIV care has become fairly complex in the developed world, the dramatic reduction in morbidity and mortality that began in 1996 and 1997 were initially achieved with just a few effective combinations: only two drug classes, no readily available viral load measurements, and in a patient population mostly pretreated with suboptimal regimens. Undoubtedly, treatment in developing countries will have to be simplified. For example, viral load monitoring will not be practical in most settings, and guidelines that focus on clinical evaluation and CD4 count may be required.
A WHO working group has been formed to select the best antiretroviral regimens for use in the developing world. Although this group is considering the same criteria used for selecting regimens in the developed world, they are likely to assign greater weight to some criteria, such as durability, ease of adherence and ease of monitoring. Even a few practical options used effectively and widely could dramatically reduce HIV morbidity and mortality in the developing world just as they did in wealthier countries in the mid-1990s.

The draft WHO guidelines
Recently, the WHO released a draft set of guidelines on the use of antiretroviral therapy in resource-poor settings. This followed a year-long process of international consultative meetings in 2001, in which more than 200 clinicians and scientists from more than 60 countries participated. These guidelines do not incorporate use of viral load; CD4 counts can be used when available. Otherwise, markers such as total lymphocyte count, increased body weight, decreases in opportunistic infections and level of physical activity are used as parameters to guide therapy.

The pros and cons of a simplified approach
Currently, western guidelines for managing patients on antiretroviral therapy (ART) use the polymerase chain reaction (PCR) technique to estimate viral loads, and CD4 cell counts to estimate the degree of immunodeficiency. An algorithm based on these two surrogate markers is now used to guide physicians on the impact of ART on a patient’s health, risk of developing opportunistic infections and prospect of disease-free survival. Viral load and CD4 counts help determine when to start therapy, and also monitor a patient on therapy. The significance of CD4 count is that it determines the degree of immunodeficiency. The viral load helps predict the rate of decline of CD4 cells, and is thus an early prognostic indicator. It is also a direct measure of the efficacy of ART. Thus, both these markers serve as sound objective parameters.
The use of viral load as well as CD4 cell counts is the time-tested method of monitoring patients. Moreover, an increase in viral load in a previously well-controlled patient signals treatment failure long before clinical symptoms develop. Also, indiscriminate use of antiretrovirals based on clinical judgement alone may lead to problems of resistance.
However, clinical monitoring may now become the most feasible tool, in order to simplify therapy. A “no-tech” minimum standard can be developed for diagnostic and treatment evaluation, which lays out basic criteria and clinical markers for monitoring patients on ART. The simplest approach, “syndromic” management of HIV, relies on physical symptoms rather than laboratory values to gauge the impact of therapy on disease status. The appearance or disappearance of physical signs of disease can help doctors determine when to start or switch a given therapy and to assess side effects, drug resistance and drug failure. Syndromic management can be used as an adjunct to or even in place of more expensive viral load or CD4 counts. Moreover, the use of this low-tech monitoring strategy for Africa or Asia does not rule out future use of the gold standard of viral load, should simpler and cheaper techniques be developed.

Conclusion
The need for more widespread use of antiretroviral therapy in the developing world is very clear. Equally clear are the objections that have been raised regarding the feasibility of such an undertaking. However, a close inspection of these objections serves to define the challenges and the means of addressing them. The simplified approach outlined in the recent draft WHO guidelines may represent an important step in increasing the use of antiretroviral therapy in developing countries.