Meeting Summary Overall, no empirical evidence exists that viral resistance and non-adherence are bigger problems in developing countries than in developed countries. The current unregulated availability of antiretroviral drugs in developed countries, however, is calculated to accelerate the emergence of drug resistance. Minimization of drug resistance will best be promoted not by slowing the introduction of ARVs in developing countries but rather by ensuring that distribution of ARVs occurs in the context of policies, practices and procedures that promote rational ARV use and encourage patient adherence. On 17-18 June 2003, the Global HIV/AIDS Program of the World Bank in collaboration WHO and the International HIV Treatment Access Coalition (ITAC) hosted a meeting of leading HIV/AIDS clinical and public and community experts from throughout the world to examine and assess available evidence on antiretroviral (ARV) drug resistance and to make recommendations to the Bank on minimizing the emergence of drug resistance in Bank-supported ARV treatment programs. Participating experts included leading researchers and public health authorities from sub-Saharan Africa, Asia, the Caribbean, Europe, North America, and South America, as well as senior officials from the World Health Organization, UNAIDS, the US Department of State, and the Global Fund to Fight AIDS, Tuberculosis and Malaria.
The Bank has been involved in fighting HIV/AIDS since 1986 and now has programs in all regions. However, with the exception of Brazil and India, there were few major projects until the Multi-Country HIV/AIDS Programs for Africa ($US 1 billion) and the Caribbean ($US 155 million). The Russia Tuberculosis and AIDS Control Project for 150 million was approved in April 2003. For the poorest countries, the Bank provides HIV/AIDS assistance on a 100% grant basis.
Although the Bank's HIV/AIDS assistance has historically focused primarily on HIV prevention and care, and general capacity-building programs, the Bank now includes substantial efforts in expanding access to ARVs and in strengthening national health care delivery systems. The Bank convened this expert consultation to promote agreement on strategies to minimize ARV resistance and adherence to treatment in resource-poor settings, advance programmatic collaboration between the Bank and other key donors and stakeholders, and generate clear guidance for the Bank's task team leaders with respect to expanding HIV/AIDS treatment programs.
This report briefly summarizes the meetings proceedings. Basic Facts About HIV-1 Resistance
Resistance develops naturally, in response to the selective pressure from drugs or from the body's own immune system. In particular, HIV's error-prone replication machinery and the rapid turnover of the HIV population facilitate viral variability. Suboptimal ARV regimens lead swiftly to emergence of drug resistance.
Even after resistance emerges, most combination ARV regimens (known as highly active antiretroviral therapy, or HAART) retain partial activity, and most patients continue to experience clinical benefits. Immunologic tests also reveal sustained benefits to the body's immune system even in the presence of viral resistance.
In the U.S., 50% or more of all ARV-treated patients exhibit viral resistance, and 5-15% of newly infected patients in North America and Europe have resistant virus. The high prevalence of drug resistance in developed countries stems principally from the widespread use of suboptimal regimens (primarily mono- and dual therapy) in the pre-HAART era (i.e., before 1995-96).
Since the early HAART years, regimens have been developed that are less susceptible than earlier regimens of fostering drug resistance. Experience in developed countries underscores the importance of prescribing regimens that are as potent and as simple as possible - to maximize viral resistance, optimize patient adherence, and minimize infectivity. Bringing ARV Treatment to Scale in Brazil
In 1996, a presidential decree mandated free, universal access to ARVs through Brazil's public health system. By December 2002, Brazil had provided ARVs to an estimated 125,000 people, accounting for more than one-third of all people in developing countries on such regimens.
Treatment scale-up has had a momentous impact on the course of Brazil's epidemic. Since 1996, AIDS-related mortality has declined between 40-70%. HIV-related morbidity has dropped by 60-80%, and the country has experienced a seven-fold decline in HIV-related hospitalization. National authorities estimate that ARVs have enabled the country to avert 58,000 new AIDS cases and 90,000 AIDS-related deaths.
Although the prevalence of drug resistance has increased as ARV access has expanded, Brazil's rate of resistance is substantially lower than in developed countries. In 2001, 6.6% of new infections involved drug-resistant strains, a rate that is roughly one-third to one-half of that reported in North America and parts of Western Europe. Brazil's success has benefited from strong political leadership, the provision of adequate national resources, and the development of strong partnerships between government and civil society. Surveys also indicate a high rate of patient adherence to prescribed regimens, with 73% of patients on ARVs in seven Brazilian states reporting at least 95% adherence in the prior three days. Other ARV Programs in Developing Countries
Meeting participants heard presentations on ARV projects in Burkina Faso, Haiti, Senegal, South Africa, and Thailand. Experiences in Haiti and South Africa are briefly summarized here.
An ARV project in rural Haiti, administered by Partners in Health, integrates HIV prevention and treatment, using a directly-observed therapeutic approach borrowed from experience in TB control. The program also focuses on TB diagnosis and treatment, prevention and treatment of sexually transmitted diseases, and prenatal care (including prevention of mother-to-child transmission and care of adverse third trimester events).
The Haiti project promotes adherence through, among other things, use of accompagnateurs, who visit patients daily to ensure they are taking their medications. Selected by the patients themselves, accompagnateurs must be able to read and write and be at least 20 years of age. They receive extensive training on TB and HIV, including medications and their side effects, confidentiality, referral systems, and strategies for promoting adherence. Accompagnateurs are supervised by the head nurse and receive a monthly salary.
The Partners in Health program is currently following more than 3,000 patients living with HIV/AIDS and providing ARVs (DOT) to more than 400 patients. Eighty-six percent of patients on ARVs have suppressed viral loads, all have experienced weight gain and other improvements in health, and fewer than 10% have required medication changes due to side effects.
In the Khayelitsha township near Cape Town, South Africa, Médicins sans Frontieres emphasizes nurse-based care in a primary care setting. The MSF project relies on generic medications and seeks to integrate HIV, TB and STD treatment services. The program includes standardized regimens, laboratory monitoring, and patient-centered adherence support strategies.
The Khayelitsha project provides ARVs to more than 400 patients. Median weight gain at six months is 8.8 kg, and at 12 months there is an 83% survival rate and a 70% reduction in opportunistic infections. Adherence rates are as high as those reported in developed countries, and 91% of patients have undetectable viral loads at six months. Elements of Effective Programs
A survey of experience thus far in distributing ARVs in developing countries reveals that successful programs rely on - - Simplified, standard regimens of fixed-dose therapies,
- Simplified clinical monitoring,
- Provision of consumer-friendly adherence support,
- Maximum use of available human resources (including non-professionals, families, and community members),
- Active community involvement, and
- Integration and phased scale-up.
Issues of Drug Resistance and Adherence
Overall, no empirical evidence exists that viral resistance and non-adherence are bigger problems in developing countries than in developed countries. The current unregulated availability of antiretroviral drugs in developed countries, however, is calculated to accelerate the emergence of drug resistance. Minimization of drug resistance will best be promoted not by slowing the introduction of ARVs in developing countries but rather by ensuring that distribution of ARVs occurs in the context of policies, practices and procedures that promote rational ARV use and encourage patient adherence.
In collaboration with partners, WHO is in the process of initiating a global HIV drug resistance surveillance program. The WHO program will assess geographical and temporal drug resistance prevalence, improve understanding of the factors that lead to resistance, and help identify strategies to minimize the appearance, evolution and spread of drug resistance. World Bank Support for ARV Treatment Programs
Participants in the meeting expressed clear support for the Bank's provision of financial assistance for scale-up of ARV treatment programs. Participants recommended that the Bank prioritize the purchase and delivery of treatments (as opposed to expensive diagnostics), actively work to empower health care workers and local communities, and promote the use of high-quality medications. In particular, the importance of rapid scale-up was strongly emphasized.
According to participants, the Bank should avoid exclusively medical models that omit psychosocial interventions or fail to involve communities. In addition, it was felt that the era of small pilot projects had passed and that emphasis should be placed on speedy expansion of treatment access. Recommendations
Participants made the following findings and recommendations -
 Scale-Up and Speed - Treatment scale-up is an urgent global necessity. Donors should prioritize the provision of financial and technical assistance to facilitate rapidly expanded access to ARVs and other HIV/AIDS treatments.
- Dramatic expansion of treatment access should occur immediately and should not await the results of additional pilot studies.
- Sustainable capacity should be developed as programs are expanded.
- Capacity Development
- To ensure the success of ARV treatment programs, health care delivery systems must be significantly strengthened in developing countries.
- Treatment initiatives must help develop and sustain human capacity, with particular attention to human resources beyond health care systems.
- To increase long-term capacity, donors should help strengthen and sustain medical and nursing education programs in developing countries.
- Adherence
- Treatment programs should include mechanisms to enhance patient adherence.
- Additional research is needed to identify optimal strategies to promote patient adherence.
- Monitoring and Evaluation
- As ARV treatment programs are expanded, they should be carefully evaluated.
- Studies should assess the impact of treatment scale-up on human behavior.
- Strong support is needed for the development and implementation of measures to monitor ARV resistance.
- Research should focus on strategies to improve the quality and effectiveness of ARV treatment programs.
- ARV Regimens
- Countries should identify standardized first- and second-line treatment regimens.
- Both brand-name and generic drugs are appropriate for use in treatment programs.
- Research is needed to help identify optimal drug combinations to minimize drug resistance.
- Partnerships
- ARV treatment programs should actively involve patients, their families, and their communities.
- Key donors - including the Bank, the U.S. government, and the Global Fund to Fight AIDS, Tuberculosis and Malaria - should coordinate efforts to maximize treatment coverage.
- Policy Issues
- The Bank should continue its active role in the development and implementation of global AIDS strategies.
- Donors should ensure that funded projects have access to an uninterrupted supply of high-quality ARVs.
- The prices of ARVs in developing countries should be further lowered.
- Key stakeholders should facilitate the development of regional capacity to manufacture ARVs.
- Accelerated research and development efforts are needed on HIV-related issues in developing countries.
For more information, please contact:
Global HIV/AIDS Program
1818 H Street, NW MSN # G8-802
Washington DC 20433 USA
Tel: (202) 202 473-9414
Fax: (202) 522-3235
Email: wbglobalhivaids@worldbank.org |
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