Scaling Up Antiretroviral Therapy for Developing Countries -- We Can Walk and Chew Gum at the Same Time           Mauro Schechter, MD, PhD   

Less than a decade ago, HIV infection was almost universally characterized by a gradual but inexorable destruction of the immune system, opportunistic infections, and finally death. In developed countries, the advent in 1996 of highly active antiretroviral therapy (HAART) completely modified this picture, with dramatic changes in morbidity and mortality rates. Moreover, antiretroviral therapy was soon shown to be a highly cost-effective intervention.^[1] Nonetheless, the high cost of these medications virtually limited their use to the most affluent societies. In fact, in 2002, The World Health Organization (WHO) conservatively estimated that although over 6 million people in developing countries were in immediate need of antiretroviral therapy, less than 4% were on treatment, half of them in Brazil.

Since the International Conference on AIDS in Durban, South Africa, in 2000, most people working in HIV/AIDS research, healthcare, and policy have accepted that expanding antiretroviral therapy to people living in developing countries was a moral, social, political, and economic imperative. Although several international initiatives have since been launched, the actual number of persons being treated still falls far short of the actual need. Additionally, many contend that unless a support laboratory infrastructure is in place with trained personnel available, large-scale provision of antiretroviral therapy will only lead to substandard treatment programs, thus compromising individual treatment outcomes and creating an epidemic of drug-resistant viruses. Hence, on the surface, the field seems to be facing a dilemma: Which should come first, the building of capacity or the provision of drugs?

A program for the provision of free antiretroviral therapy was started in Brazil in 1991. In 1996, advocacy and mounting societal pressure culminated with a special law being passed to ensure free and universal access to antiretroviral therapy to all individuals who qualified for treatment according to periodically revised guidelines developed by an independent panel. In parallel, a network of HIV testing sites, primary-care facilities, and laboratories was progressively established around the country. At first, monitoring was mostly based on clinical and simple laboratory parameters. As the program matured, CD4+ cell counts and viral load measurements became progressively more available. In parallel, a large training program was implemented. Since Brazil is a country of continental dimensions and equally large inequalities, the quality and the level of sophistication of the infrastructure that is presently available in these services is still highly variable. Additionally, the Brazilian program tightly linked prevention and treatment. A program of local production of generic versions of drugs that were not patent-protected according to contemporary local laws was also implemented. Confronted with this policy, the pharmaceutical industry was compelled to come to the negotiating table and to sharply reduce the prices of other antiretrovirals. At present, over 120,000 Brazilians are receiving free drugs and treatment from the government. As a direct consequence of this program, morbidity and mortality rates have sharply declined. In fact, graphs depicting these declines are indistinguishable from graphs that portray the impact of the introduction of antiretroviral therapy in the United States and Europe. Moreover, by 2000 the number of HIV-infected people in Brazil was estimated to be half of what had been predicted by international agencies a decade before. In summary, in the highly successful Brazilian program, provision of drugs and capacity building occurred simultaneously, with the existence of one reinforcing the other.

Skeptics can always argue that Brazil is a relatively sophisticated middle-income country. As such, its experience would not be transposable to more resource-limited settings. At the 2nd IAS Conference on HIV Pathogenesis and Treatment, several presentations made during the opening ceremony, in a plenary talk, and in a session on scaling up antiretroviral therapy showed that antiretroviral therapy could be successfully used in developing countries. Reports from Botswana, Barbados, Zambia, Malawi, India, and other countries demonstrated that rapid scaling up of antiretroviral therapy is an achievable goal. Several studies conclusively demonstrated that adherence to treatment, failure rates, and development of virologic resistance in these settings are, at the very least, no better or no worse than in developed countries.

For example, N. Durier^[2] reported that in Malawi, in a program implemented by Médecins Sans Frontières, over 90% of patients reported more that 80% adherence, which is reflected in a median CD4+ cell gain at 12 months of 133 cells/mcL. In a report from Barbados, S.A. Adomakoh^[3] presented data demonstrating an association between provision of antiretroviral therapy and a decrease in hospital admissions, resulting in a shift from inpatient care to outpatient care. These and other data indicate that doubts about the cost-effectiveness of such intervention in developing countries do not stand close scrutiny.^[4]

Since the Durban conference, the price of most drugs has been dramatically reduced, many fixed-dose combinations that allow for once- or twice-daily dosing have become available, and antiretroviral therapy has been shown to be cost-effective even in severely resource-constrained settings. A variety of strategies have been tested and proven to work. It has also been conclusively demonstrated that treatment and prevention are mutually reinforcing elements of a comprehensive approach. In addition, it has been shown that provision of drugs and capacity building can occur simultaneously. Of course, there are still enormous organizational, operational, logistical, and technical challenges to be overcome. However, we have learned that the scaling up of antiretroviral therapy is possible and feasible, and that by now we have a very good idea of how to do it. Science has given us the tools to stop the epidemic. It is now a matter of translating scientific knowledge into action.

References

1. Freedberg KA, Losina E, Weinstein MC, et al. The cost effectiveness of combination antiretroviral therapy for HIV disease. N Engl J Med. 2001;344:824-831.
2. Durier N. Treatment of HIV disease with HAART in Chiradzulu district, Malawi. Program and abstracts of the 2nd IAS Conference on HIV Pathogenesis and Treatment; July 13-16, 2003; Paris, France. Abstract 112.
3. Adomakoh AS, Adomakoh NKP, Gaskin A, Roach TC, Abayomi A, Fraser HS. Cost implications of providing scaled-up HAART in a middle income microstate. The Barbados experience IV. Program and abstracts of the 2nd IAS Conference on HIV Pathogenesis and Treatment; July 13-16, 2003; Paris, France. Abstract 113
4. Boulle et al, AIDS 2003.