Offering lessons for treating HIV/AIDS to Pepfar
16 December 2003
INTRODUCTION In the developing world today, over 40 million people are living with HIV/AIDS. Of the more than six million people in urgent clinical need of antiretroviral (ARV) treatment, only 400,000 have access to it, and one-third of them live in one country, Brazil. An estimated 8,000 people die each day of AIDS-related complications. These are premature, avoidable deaths. Currently, Médecins Sans Frontières (MSF) is providing ARV treatment as part of a comprehensive continuum of care for approximately 10,000 people living with HIV/AIDS in 42 projects in 19 countries in Africa, Asia, Latin America, and Eastern Europe. MSF is an international medical humanitarian organization with field operations in nearly 80 countries and the recipient of the 1999 Nobel Peace Prize. We have learned important lessons about both the benefits and challenges of providing ARV treatment in resource-limited settings and are in the process of adapting our approach to AIDS treatment to better fit the real-life conditions faced in developing countries. Our projects are using treatments with fewer pills, relying less on sophisticated laboratory tests, taking better advantage of the skills and resources of existing health care professionals such as clinical officers and nurses, and decentralizing the point of care to district hospitals and health posts. In addition, we have produced several reports, some of which are joint publications with the World Health Organizations (WHO), UNAIDS, and UNICEF, to help other providers of ARV treatment-including governments, non-governmental organizations (NGOs), and community-based organizations-identify sources, prices, and patent status of needed medicines and assist with strategies for efficient procurement of medicines. We have also participated actively in the development of the WHO initiative to scale up treatment to at least three million people by 2005 ("3x5"). While our ARV treatment programs have had a significant impact on the individuals and communities with whom we work and have demonstrated the feasibility of providing ARV treatment in resource-limited settings, they are relatively small-scale, and we have neither the capacity nor the mandate to provide the wide-scale access to treatment that is so urgently needed. That responsibility rests with national governments. We do, however, feel it is our responsibility to share our experience and impart the lessons we have learned in order to inform efforts to scale up access to treatment, including the United States President's Emergency Plan for AIDS Relief (PEPFAR). This is why we would like to highlight the following critical issues, which in our experience must be considered as utmost priorities as the U.S. government begins to implement its PEPFAR:
Simplifying treatment protocols, particularly by minimizing patients' pill burden;
Decentralizing and adapting clinical approaches to treatment and monitoring;
Decreasing the prices of medicines, ensuring efficient procurement of medicines, and making treatment available for free;
Involving communities, including people living with HIV/AIDS, in treatment programs;
Promoting research and development of new tools to respond to specific needs in high-prevalence countries; and
Ensuring coherence, and avoiding duplication, with national policies in developing countries and international initiatives to scale up access to treatment.
MSF'S AIDS TREATMENT EXPERIENCE
MSF has been caring for people living with HIV/AIDS in developing countries since the early 1990s. In 2000, MSF started to provide ARV therapy in addition to other services. Approximately 10,000 people living with HIV/AIDS, including nearly 500 children, are currently on ARVs in 42 MSF projects in 19 countries worldwide. These countries include Burkina Faso, Burundi, Cambodia, Cameroon, China, Democratic Republic of Congo, Guatemala, Honduras, Indonesia, Kenya, Laos, Malawi, Mozambique, Myanmar, Rwanda, South Africa, Thailand, Uganda, and Ukraine.
MSF provides ARV treatment in both urban and rural settings, and in almost every project works within public sector health facilities-including primary care clinics/community health posts, district hospitals, and provincial hospitals-in collaboration with national, provincial, or district departments of health. Clinical eligibility criteria are, for the most part, uniform throughout MSF projects (< 200 CD4 cells or 15% for children), though some projects are increasingly initiating treatment in very advanced patients on clinical grounds. In MSF projects, treatment is provided free of charge.1
MSF does not offer ARV treatment in a vacuum, so we aim to integrate treatment into a continuum of care that includes prevention efforts (e.g. health education, condom distribution, and prevention of mother-to-child transmission programs), voluntary counseling and testing, treatment and prevention of opportunistic infections, nutritional and psychosocial support, and palliative care.
MSF expects the total number of patients treated in its projects to reach 25,000 in 25 countries by the end of 2004.
MSF looked at clinical data for 10 of its larger projects, which began during the period 2001-20032 and found that 87.6% of a total of 6,134 patients who initiated treatment were still on ARVs, while 9.9% died and 2.0% were lost to follow up or stopped treatment. In these 10 projects, MSF has observed that > 90% of patients began treatment with an advanced HIV status (stage 3 or 4 according to WHO criteria).
Where efficacy data were available (from eight of 10 projects), first-line treatment failed in an average 0.7% of cases. Patients showed a median CD4 cell gain of 145 after 12 months (based on data from seven projects). In countries where viral load is available, such as South Africa, MSF observed that 87.7% of 146 patients studied presented with an undetectable viral load after six months.
Also in South Africa, for example, the frequency of opportunistic infections decreased dramatically (e.g. the occurrence of tuberculosis decreased by three times once people started ARVs), people's weight after one year on ARV therapy increased by an average of 22 pounds, and although some patients experience mild side effects at initiation of therapy, these vanish after a few weeks. The most commonly prescribed first-line regimen in MSF projects is a fixed-dose combination (FDC) of stavudine (d4T)/lamivudine (3TC)/nevirapine (NVP).
Adherence rates are high. For example, adherence rates exceeded 90% of patients in MSF projects in Chiradzulu, Malawi; Maputo, Mozambique; and Pnohm Penh, Cambodia. Similarly, in Khayelitsha, South Africa, nine out of 10 people on ARV treatment in the MSF project can be considered highly adherent, meaning that they take at least 95% of their tablets.
LESSONS LEARNED FROM MSF'S ARV EXPERIENCE
By providing ARV treatment in diverse settings, we have learned several clear lessons that could be helpful in designing and implementing the PEPFAR:
Adhering to treatment must be made as easy as possible. For this reason, we are working to have 80% of our patients on triple FDCs by January 2004. Today, 70% of patients and nine out of the 10 largest MSF projects are using triple FDCs as their first-line treatment. That is, patients are taking the three different antiretroviral drugs they need in the form of one pill, twice a day. Taking a smaller number of pills per day facilitates adherence, which encourages better clinical results and also lessens the risk of drug resistance, as it is impossible to take partial doses. The FDCs MSF uses, which have been pre-qualified by WHO, are also the most affordable combinations available worldwide and have significant distribution advantages (procurement and stock management).
Decentralize and adapt
Treatment protocols must be designed in a way that facilitates access even for the poorest and most vulnerable people in remote settings where there are few hospitals, few doctors and even fewer laboratories. In Chiradzulu, Malawi, for example, MSF has set up mobile treatment clinics at each of the 10 local health centers, making treatment more accessible to communities. Basic patient care and follow-up is delegated to nurses and health workers (for medical monitoring) and community counselors (for education, adherence support and treatment literacy).
MSF follows uniform guidelines for treatment minimizing use of laboratory tests; in many cases, treatment begins after a positive HIV test and clinical assessment by trained staff. More difficult cases are referred to the district hospital. This has allowed the number of patients under treatment in the district to rise quickly, to a rate of 250 new patients in October 2003 alone.
Decrease the price of medicines and ensure availability even for the poorest
The lower the price of medicines, the more patients can be treated and the more sustainable treatment is in the long term. Globally, the prices of AIDS drugs have dropped by over 98% in less than three years. In MSF projects, the price of first-line treatment has ranged from $270 to $593 per person per year, and we now have access to WHO pre-qualified FDCs that cost less than $1403 per person per year.
These FDCs are available only from generic manufacturers due to patent barriers. In MSF's experience, crucial factors in bringing about lower prices for ARVs include government commitment to centralized procurement, overcoming patent barriers when necessary, and fostering generic competition. The cost of treatment for the patient should never be a barrier, and that means treatment will have to be free for the majority of patients. The cost of drugs is frequently cited as a reason for treatment interruptions.
Involve the community
The knowledge and meaningful participation of people living with HIV/AIDS is key to the success of treatment. At its HIV clinics in Khayelitsha, South Africa, MSF and grassroots treatment advocates have fostered community-based education programs. Through carefully designed patient-centered adherence programs (not directly observed therapy), people on ARVs in MSF programs have the support of their peers and of trained counselors. Community mobilization, in partnership with medical services, has had a powerful effect on the community, decreasing stigma and discrimination, and supporting prevention efforts. In Khayelitsha, there has been significant increases in the distribution and use of condoms, the number of sites providing voluntary counseling and testing, and the uptake rate of testing.
According to a study conducted by the Center for AIDS Development, Research and Evaluation (CADRE) and the South African Department of Health, the self-reported condom use at last sexual intercourse, willingness to use a female condom, and consent to an HIV test in the Khayelitsha community is the highest in South Africa.
Urgently promote research and development of new tools
It will not be possible to solely base scaling-up efforts on existing tools. New tools will have to be developed to respond to specific needs in high-prevalence countries. For example, at present, ARVs are not well-suited for use by children, so fixed-dose liquid formulations for infants and low-dosage or breakable FDC tablets for children are needed. The pharmaceutical industry is not going to spontaneously fill existing and future gaps such as easy-to-use first-line treatments for children, simplified second-line treatments and simplified diagnostic tools (e.g. semi-quantitative tools to measure CD4 and viral load).
The public sector, with leadership from WHO, should therefore seek to define and lead the work on this research agenda. This needs to be a part of the overall U.S. global AIDS strategy. There is also an urgent need for operational research, for example on pediatric treatment, management of HIV/TB co-infection, ideal second-line regimens, and structured treatment interruptions.
Ensure coherence with national and international efforts
During the past year, there have been several positive developments at the national and international level related to expanding access to AIDS treatment, including the launch of the WHO's "3x5 initiative" (three million people on AIDS treatment by the end of 2005); the announcement by several countries including South Africa of plans to develop national AIDS plans that include ARV treatment; the continued reduction in the prices of ARVs; the disbursement of funding from the Global Fund to Fight AIDS, Tuberculosis and Malaria; and the implementation by some countries of the World Trade Organization (WTO) Doha Declaration on TRIPS and Public Health.
If PEPFAR is to meet its stated objectives, it must be designed to work in collaboration with existing initiatives. Because PEPFAR is just one part of a global U.S. AIDS strategy, efforts must be made to ensure that U.S. policies do not contradict or undermine the ability of countries to expand access to care and treatment. For example, the U.S. must commit its fair share of financial resources to other international AIDS treatment initiatives and support flexibilities in international intellectual property rules, rather than undermine them in regional and bilateral trade agreements.
1 Except in Cameroon, due to government policy requiring entrance fee.
2 The projects observed were Chiradzulu and Thyolo in Malawi; Uganda; Kenya; South Africa; two projects in Maputo in Mozambique; Cameroon; Cambodia; and Thailand.
3 Due to negotiations with generic manufacturers brokered by the Clinton Foundation.
Townhall Meeting on the President's Emergency Plan for AIDS Relief (PEPFAR)
Delivered by Rachel M. Cohen
U.S. Director, MSF Campaign for Access to Essential Mediccines
December 16, 2003