Antiretroviral Therapy Provision in the Developing World

Michelle Osborn

 

“Lack of access to antiretroviral treatment is a global health emergency… To deliver antiretroviral treatment to the millions who need it, we must change the way we think and change the way we act.”

-Lee Jong-wook, Director-General of the World Health Organization[1]

 

 

            In 1981 the world was confronted with a new disease, the acquired immunodeficiency syndrome (AIDS), which resulted from the human immunodeficiency virus (HIV).[2],[3] Considering initial AIDS diagnoses were among homosexual men in the United States, the threat of a global epidemic did not appear imminent. Two decades later, however, HIV/AIDS has emerged as one of the world’s most devastating diseases. Moreover, HIV/AIDS has quickly become a disease associated with poverty. 95% of the 40 million people suffering from HIV/AIDS live in the developing world.[4] AIDS has claimed over thirty million lives, including the three million deaths that occurred in 2003. UNAIDS estimates that 14,000 people are infected daily and over half of these new infections occur in youth, ages 15-24.[5] As of 2004, neither a cure nor a vaccine has been developed. However, within the last eight years medical technology has produced antiretroviral drugs (ARVs), which have improved the quality of life and prolonged survival for HIV infected persons. Treatment has reversed the outcome of HIV/AIDS from that of a death sentence to a chronic illness.

At the end of 2003 approximately 6 million people in the world were in need of antiretroviral drugs; 4.1 million of these persons live in Africa and only 50,000 of them currently receive these life saving drugs.[6] In 2002, UNAIDS estimated that only 5% of the total number of patients living with HIV/AIDS in the developing world received antiretroviral drugs. In the past four to six years there has been increasing demand for affordable and accessible antiretroviral drug provision to the millions of individuals suffering from HIV[7]/AIDS. This demand has resulted in the development of generic drugs, drastic price reductions by pharmaceutical companies, and even policy changes related to the provision of essential medications.[8]  Despite this demand and the recent reductions in drug costs, there are those who argue that antiretroviral drug provision is not cost-effective nor is it a feasible task for developing nations to undertake. Moreover, there are concerns related to drug resistance, adherence, and long-term sustainability of antiretroviral therapy. Heated debates have thus taken place arguing for and against increased provision of antiretroviral drugs. Moreover, international trade laws, patents, and policy further complicate the issues raised within this debate and the ability to provide treatment to the developing world.

This chapter will outline the various issues and concerns related to the provision of antiretroviral drugs in the developing world and examine successful accounts of antiretroviral drug programs in Brazil and Haiti. Moreover, considering that developments related to antiretrovirals and their provision are constantly changing, this chapter also aims to provide the reader with a comprehensive list of resources for future reference.

 

Anti-Retroviral Therapy: The Basics

Before outlining the variant issues surrounding antiretroviral drug access, provision, and distribution it may be helpful to initially define and describe basic attributes related to antiretroviral therapy. Antiretroviral therapy (ART) refers to the use of a combination of antiretroviral drugs (ARVs). Antiretroviral drug combinations, known as “drug cocktails” or “triple therapy” have been available to the public since 1996.[9] Another acronym for ART is HAART, meaning highly active antiretroviral therapy, which refers specifically to “triple therapy” or three drug combinations.[10] HAART is widely used in within the literature and therefore is the choice term for this chapter. The goal of HAART is to suppress the HIV replication process, which further debilitates the immune system. HAART slows down this process by suppressing the virus (or viral load) to the point that it is undetectable. More than 50 clinical trials have shown that the use of multiple drug combinations delay patients’ corporal debilitation by suppressing viral replication and improving immunity. While antiretroviral therapy does not cure HIV/AIDS, HAART does increase patients’ chances for maintaining long-term control of their HIV infection through improving immune function. [11] Moreover, HAART can improve patient quality of life and also prolong chances for survival.

While HAART has the ability to drastically improve the life of HIV/AIDS patients, it is important to point out the potential negative aspects associated with antiretroviral therapy as well. Clinical studies have shown that such ARV combinations usually achieve viral suppression in 90 to 95% of patients, however, approximately only half of all patients achieve undetectable viral load levels with HAART.[12] Moreover, after stopping HAART, viral loads have been shown to rebound to levels higher than those prior to treatment. In addition to not always being effective, treatment can be quite complex, it requires strict adherence, and patients can suffer multiple adverse side effects. HAART consists of taking multiple drugs- typically a combination of three ARV drugs, which must be taken multiple times at the same time each day. In order for HAART to be effective, patients must adhere to a strict daily drug regimen otherwise treatment failure is likely to occur. Even with strict adherence rates, drug resistance may occur. The emergence of drug resistant HIV is one of the primary challenges to HAART and is also one of the major concerns in implementing nation wide HAART provision in the developing world.

            Beyond drug resistance, patients may develop a variety of toxicities to ARV medications and multiple side effects, including but not limited to gastrointestinal problems, insulin resistance, fat redistribution, rashes, and central nervous system complications. Most of these side effects can be mitigated through the use of additional medications. However, attaining additional medications could be particularly challenging for many resource-limited countries.[13]

In attempts to standardize and simplify antiretroviral therapy, drug companies Cipla and Ranbaxy developed “fixed-dose combination” (FDCs) drugs—pills that contain two or three AIDS drugs in one tablet.[14] Thus, patients with access to FDCs only have to take one pill twice a day. [15] On December 1, 2003, AIDS Day, the World Health Organization (WHO) approved the first “fixed-dose combination” (FDC) drug. WHO argues that single-pill combinations will greatly improve adherence, increase ease in use and the ability to distribute drugs for patients urgently needing HAART in developing nations.[16]

 

International Trade Laws, Patents, and the Generic ARV Drugs

Intellectual property, international trade laws, and patents have had a direct impact on the provision of HAART in the developing world, primarily due to the high costs of pharmaceutical drugs. It has been argued that patents held by pharmaceutical companies create a monopoly on antiretroviral drugs, which result in decreased accessibility and high prices. Moreover, such patents limit the abilities of developing countries, especially those tied to the World Trade Organization, to produce or attain affordable medications. Pharmaceutical companies have in the past argued that high costs of ARVs is essential to recouping costs related to drug research and development. However, campaigns, such as the Treatment Action Campaign[17] and Doctors Without Borders Access to Essential Treatment campaign,[18] international critiques of patent laws, and even White House executive orders have challenged the actions of pharmaceutical companies.

The World Trade Organization (WTO) in 2001 in Doha, Qatar developed the Ministerial Declaration on the Trade-Related Aspects of Intellectual Property Rights (TRIPS) Agreement and Public Health. This became known as the Doha Declaration, ultimately placing protection of public health over the protection of private commercial interests. Thus, essentially giving developing countries the right to develop and provide access to life-saving drugs despite patent laws.[19]

The Doha Declaration allowed for a wider distribution of generic ARVs, resulting in a decrease of treatment cost from US$10,000 to US$200 per year, per patient in less than three years time.[20] Countries are now able to produce their own generic medications, however, few developing countries have been able to do so. However, this may soon change. Brazil has successfully managed to produce ARV’s and is now offering to transfer their drug production know how to countries who wish to produce generic drugs.[21]

However, concerns over increasing pressures to restrict generic competition continue to exist. Gunaratnam of Doctors Without Borders fears that the WTO and the power of the pharmaceutical industry’s lobby will continue to place pressure on legislators to restrict generic supplies and developing nation’s ability to export and import generic drugs. Latin America is already experiencing pressure from the Free Trade Area of the Americas (FTAA), who have proposed a regional trade agreement, which would limit Latin American countries’ rights to foster competition in the private sector with medicines that are currently patented as well as limit their ability to reduce high prices on medicines needed during emergency situations. Thus, essentially reducing the protections set aside by the Doha Declaration.

Even in the midst of pressures by free trade associations, WTO, and pharmaceutical companies, demand for affordable and accessible HIV/AIDS treatment continues to exist and maintains political pull. In the fall of 2003, former President Bill Clinton brokered a deal with the following four drug companies, which produce first-line triple treatment regimens: Cipla, Ranbaxy, and Matrix of India and Aspen of South Africa.[22] These companies have agreed to cut costs for HAART by 1/3 to 1/2 the original price. Thus, placing current HAART treatment at $140 per patient/per year.[23] This is an immense accomplishment and reduces the barriers for extensive and effective provision of HAART to the developing world.

Trade practices and patents are essential to the accessibility and affordability of antiretroviral therapies and to the optimization of public health promotion in the developing world. Such political and economic issues directly impact public health and as seen here can either promote or restrict access to life saving medications for millions of persons.

 

HAART Provision in Developing Countries:

            The provision of antiretroviral drugs in developing countries, especially considerations regarding national coverage, is a controversial topic in that it raises a number of issues ranging from politics to economics to human rights. In order to fully understand the various points of contention surrounding HAART, it is essential to discuss the very issues debated by scholars, health professionals, policy makers, economists, and activists. The following section outlines the arguments made in favor for and against greater access to, provision and distribution of antiretroviral therapy in the developing world.

 

Considering the Cons: Negative Attributes Associated with HAART

            Scholars ranging from economics to medicine to social sciences are engaged in the debate on the provision of antiretroviral treatment in resource-limited countries. Those who tend to be skeptical or opposed to such provisions often focus on issues related to feasibility, cost, prevention, and drug resistance. One of the primary concerns related to HAART provision in the developing world is associated with the emergence of HIV drug resistant strains.[24] It is argued that low adherence rates result in the development of resistant strains of HIV.[25] Low adherence is thought to be related to the complexity of HAART (i.e. pill burden), adverse side effects, financial costs, and the inability of weak health systems to monitor and sustain availability of treatment.[26],[27]

Management of antiretroviral therapy, which is related to adherence, can be analyzed at the level of both the individual and the system. The administrator of the US Agency for International Development (USAID), Andrew Natsios, argued that the majority of Africans would be unable to adhere to HIV treatment because they “have never seen a clock or watch in their entire lives.”[28] Moreover, he stated that Africans, “don’t know what Western time is,” therefore they would be unable to take drugs at specific time intervals.[29]  As illustrated by Natsios’ comment, fears surrounding patients’ inability to adhere to treatment and personally manage treatment is central to the argument in favor of opposition of HAART. Beyond a patient’s ability to take medications at specific times lies the issue of nutritional requirements that play an important role in mitigating adverse side effects associated with treatment. HIV/AIDS patients in the developing world suffer from inadequate nutrition and are often unable to acquire the necessary sources of nutrition to accommodate HAART.[30] Thus, it is argued that HAART may not be as effective without nutritional supplementation, which would add to the costs of therapy.[31]

Doubts regarding the ability for developing nations to manage HAART therapy compounds concerns related to personal management of HAART. In resource-limited countries the health care infrastructure in both urban and rural areas are often overextended, strained, and under funded. This is a concern primarily because HAART requires careful monitoring of drug toxicity, blood counts, liver function, lipid profiles, therapeutic response, and viral loads—all of which require established and stable medical centers along with medical professionals to conduct and interpret testing and monitor treatment.[32] Furthermore, skepticism surrounds the ability of developing nations to sustain funding for an adequate supply of drugs, treatment of opportunistic infections, monitoring costs, diagnostic tests, and prevention. Such concerns are valid, considering most developing nations are unable to provide long-term, cost-effective treatment for more common and less complicated infectious diseases.

Many of those who oppose national coverage of HAART in the developing world argue that despite declining drug prices, treatment is not cost-effective. Stefan Hanson of the National AIDS Control Programme in Tanzania states that, “The establishment of a nationwide HAART programme…would run counter to the stress on evidence-based interventions, such as cost-effectiveness”.[33] It has been calculated that for every US$1 spent on HAART, an additional US$3 must be spent towards the development of the nation’s health infrastructure.[34] Prevention and treatment aimed at opportunistic infections and palliative care is not only thought to be more cost-effective, but some scholars argue that this approach will ultimately save more lives.[35] Elliot Marseille and colleagues compare disability adjusted life years (DALYs) of prevention and HAART. Their analysis, “suggests that for every 1 life-year gained with HAART, 28 life-years could have been gained with prevention.”[36] This is a reduction of the ratio of cost-effectiveness between HAART and prevention, which is US$350:US$12.50. Moreover, Marseille et al. comment that despite deaths among the working adult population and the increasing number of orphans, prevention remains more cost-effective. Furthermore, the seeming shift in focus away from prevention efforts towards treatment remains raises concerns.

             In addition to concerns over the potential decline in prevention-focused programs, lies the fear that a focus on HAART may fail to address the need for long-term political reform, poverty alleviation, and reform of health systems. Louisiana Lush of the London School of Hygiene and Tropical Medicine argues that the development of ARV regimens for developing countries is highly technical and managerial, thus underplaying the primary problems of “poverty, power, and equity”.[37] She challenges readers to consider “…the fundamental inequities, both global and local, that prevent health systems from providing decent health care”.[38]

In addition to issues related to drug resistance, adherence, management, and cost-effectiveness remain concerns surrounding stigma and decreasing perceptions of risk. It has been suggested that HAART, especially directly-observed therapy of antiretroviral treatment r may compromise a patient’s confidentiality and lead to stigmatization.[39] Also it has been suggested that antiretroviral therapy may lead to a decrease in perceptions of risk, thus directly increasing sexual risk behaviors.[40] Brazil reported a 3.7% increase in HIV incidence, which the Ministry of Health attributed to a decline in condom use occurring shortly after the onset of HAART.[41]

            As Marseille et al. note, these issues concerned with the provision of HAART are central to the debated and should not be dismissed simply even though they are “difficult and painful” choices to consider.[42] Instead they argue that, “This debate, if joined in good faith, could save millions of lives.”[43]

 

Pro Positions on Antiretroviral Treatment in the Developing World

            Those who oppose or are simply reluctant to support national coverage of antiretroviral drugs often argue that HAART is not entirely feasible, nor is it cost-effective, and has the potential to produce negative consequences—either through drug resistance or decline in prevention efforts. However, there are those scholars, professionals, activists, and experts who disagree, claiming that not only is HAART feasible and cost-effective, but it is an essential part of prevention. The following section addresses the various viewpoints in support of HAART in the developing world.

            Regarding management of antiretroviral therapy, pilot studies conducted in developing countries have shown that HAART projects can be carried out successfully and over long periods of time, even in resource-limited contexts.[44] Pilot studies carried out in Senegal and Uganda assessed the feasibility of HAART and both concluded that antiretroviral therapy is not only feasible, but also very effective. Researchers in Dakar, Senegal conducted a prospective observational cohort study with 58 HIV positive patients, whom they followed over 18 months. Within the first month of HAART provision, patient viral load was undetectable in 79.6% of participants. Eighteen months later, viral load suppression had been maintained among approximately 60% of patients. Moreover, CD4 cell counts increased significantly, chance for mortality decreased, and of the 51% who experienced side effects practically half of all cases were mild. 87.9% of participants reported adherence rates greater than or equal to 80% and only 2 cases of drug resistance emerged.[45] The Senegal study, “yielded clinical and biological results comparable to those seen in Western cohorts”.[46] Similar findings are observed in the Uganda study, which assessed HAART care of 476 HIV/AIDS patients. 88% of patients reported to adhere to treatment “about as prescribed.”[47] Such successes are also found in two South African studies, which reported 88 to 95% adherence among patients taking HAART and approximately 92% of participants maintained undetectable viral loads.[48] Furthermore, an HAART community-based initiative conducted in Haiti had similar findings, which is discussed in additional detail, later in the chapter.

            Adherence rates are particularly high throughout studies conducted in resource-limited countries and are continually observed within the developing world. Donald McNeil of the New York Times reported in September of 2003 that Africans are actually better at managing HAART than their US counterparts.[49] Adherence to antiretroviral drugs in the US and Europe is approximately 70%, 10 to 25% lower than reported adherence rates in Africa.[50] Thus, the data provides convincing evidence that patients in resource-limited settings can successfully manage HAART and further suggests that HAART adherence is just as good, if not better in resource-poor countries as compared to resource-rich ones.

            Beyond addressing adherence concerns, studies revealed that issues related to resistance and side effects were not nearly as problematic as perhaps initially anticipated. As mentioned above, studies revealed that adverse side effects were for the most part manageable and the development of drug-resistant strains was minimal. Predictions related to the proliferation of drug-resistant strains due to non-adherence of HIV therapy were in fact based upon a small study that focused on monotherapy and not HAART, which consists of triple-drug combinations. Current cross-sectional studies of adherence and resistance reveal that resistance is more likely to occur in patients who have high adherence and yet never experience complete viral suppression.[51] Farmer et al. (2001) also point out that drug resistant strains have been a problem in the US and Europe and are primary related to monotherapy, not the triple-therapy currently being provided and advocated for in the developing world.[52] Farmer et al. also suggests that the potential for drug resistant strains exists in wealthy nations, however, potential resistance does not mean that governments or health facilities refuse treatment.

Regarding concerns related to weak health infrastructures and inability to support complex care, many scholars have argued that such fears are tenuous. UNAIDS conducted pilot studies in Senegal, Uganda (mentioned above), and the Ivory Coast and “found that with a little help to set up medical infrastructure, drugs can be delivered, even to remote areas, without increasing drug resistance.”[53] Paul Farmer and colleagues reported that, “minor modifications [can] improve local capacity to care for those sick with advanced HIV disease.”[54] Furthermore, concerns regarding distribution and monitoring can be mitigated with the introduction of “fixed drug combinations” (FDCs), community-based directly observed therapy approaches to HAART (this will be discussed further later) and basic modifications to ensure monitoring supplies and education. Such successes have already been demonstrated and will be discussed later in this chapter.

In response to claims regarding prevention, advocates for increasing the provision and distribution of HAART in the developing world, claim that treatment is a necessary part of prevention. They also acknowledge that treatment and prevention must go hand-in-hand. However, they also claim that to solely focus on prevention would mean ignoring the millions of individuals already suffering from HIV/AIDS.[55] Moreover, biologically speaking, viral loads that have been suppressed at undetectable levels have been shown to reduce the risk of HIV transmission. Thus, Farmer et al. and Liechty et al. argue that HAART could become an essential part of prevention.[56] From a social stance, treatment is believed to reduce stigma and decrease the fear of receiving a positive HIV status. The HIV Equity Initiative in Cange, Haiti has found that even though AIDS is still stigmatized, access to therapy has helped to alleviate stigma.[57] Stigma alleviation is also related to prevention through helping to encourage people to break the silence surrounding the disease and to encourage people to seek testing.

One of the most debated points for and against the provision of treatment is related to the cost of care. As mentioned previously, several scholars argue that HAART is not cost-effective in the developing world, especially when compared to prevention. It should be noted that prevention is almost always cheaper than treatment, regardless of a nations development status. In addition, scholars claim that in order to have cost-effective HIV care, treatment must be involved.[58] The cost of not treating a person with HIV/AIDS includes the following: 1.) Loss of income of adult patients who make-up the work force, 2.) Loss of income of caregivers (parents, children of the elderly), 3.) Loss of patient output, 4.) Funerary expenses, 5.) Orphan care and support, 6.) Death and survivor benefits, 7.) Costs resulting from the breakdown in social cohesion networks, and 8.) Loss of social investments- i.e. education. [59] These expenses, according to Hans Binswanger of the World Bank, far exceed the cost of treatment. Especially considering that the price of treatment has dropped by more than 95% in the last 4 years.

Furthermore, economists are now encouraging nations with a high prevalence of HIV/AIDS to increase spending for HAART. Initially economists estimated that nations who have high HIV infection rates among adults would lose approximately 1% of their Gross National Product (GNP). However, it is now believed that this figure was “grossly underestimated.”[60] Hospitalization costs, the loss of markets, the loss of a trained and educated work force, the costs for orphan care, etc. have had a negative financial impact beyond initial expectations. For example, if South Africa continues to suffer from extremely high HIV prevalence rates, then the World Bank estimates that within four generations their economy will be halved. Advocates argue that treatment will have a positive effect on national development as well.[61] Thus, economists argue that it is crucial for countries with high HIV prevalence rates to scale-up provision and distribution of generic drugs.

This debate will continue to be waged and issues regarding treatment, prevention, cost, resistance, and adherence will remain important considerations central to HAART provision in resource-limited settings.

 

Success Stories:

            The following examples are brief case studies where resource-limited nations have been successful in their provision and distribution of HAART. They also represent models of care, which are currently being expanded and utilized in other parts of the world.

 

Brazil

Brazil’s response to the AIDS pandemic, especially their provision of free ARV treatment, developed out of governmental efforts, community initiative, and advocacy. Nearly 105,000 of Brazil’s estimated 600,000 HIV/AIDS patients receive free ARV treatment. Brazil has been able to avert 90,000 deaths, prevent 60,000 new cases, and 358,000 AIDS-related hospitalizations between 1996 and 2002.[62] Brazil has also managed to reduce mother-to-child HIV transmission rates from 30% to 0.02%. As of 2003, Brazil had saved more than $2 billion dollars as a result of its HIV/AIDS program. The annual STD/AIDS program is approximately US$500 million, with 60% spent on medication. Overall, Brazil’s achievement is a direct result of the holistic and national response directly tied to public health efforts and their development of locally made generic low-priced drugs.[63]

 

Haiti

Haiti is one of the poorest countries in the western hemisphere and is ranked among the poorest nations in the world. The country’s GNP is approximately US$400 and unemployment rates exceed 70%.[64] Considering HIV/AIDS is now seen as disease associated with poverty, it is not surprising that Haiti has one of the highest HIV prevalence rates in the western hemisphere. According to UNAIDS, Haiti’s national HIV prevalence rate is between five and six percent.[65] Complicating the relationship between poverty and HIV/AIDS is a weak national public infrastructure and a meager health budget of less than US$2 per person, per year.[66] Despite high HIV prevalence, impoverished living conditions, and insufficient health care, successful implementation and monitoring of highly active antiretroviral therapy (HAART) has been achieved in the rural area of Haiti, known as Cange. A community-based approach designed to provide directly-observed therapy with highly-active antiretroviral therapy (DOT-HAART) to patients with advanced HIV was developed and implemented in Cange in 1998.[67] This model was based upon the success of directly-observed therapy for tuberculosis. HIV patients were assigned to work with a community health worker who, “observes ingestion of pills; responds to patient and family concerns; and offers moral support”[68]. Social support was also offered in conjunction with personal observation and aid of medication by hosting monthly meetings for patients, offering economic assistance, and other social services. This approach was extremely successful and achieved nearly full coverage within the area of Cange. Furthermore, this community-based initiative, which currently treats approximately 100 patients, has high rates of patient compliance and managed to reduce opportunistic infections, hospital admissions as well as patient mortality.[69] In addition to these successes, patients rarely experienced side effects and very few patients have had to change treatment regimens.[70] Based on the success of the community-based initiative in Cange, DOT-HAART treatment has been scaled-up and should cover central Haiti and Port au Prince by the year 2008.[71]

 

Conclusion: Antiretroviral Therapy- Considerations for the future

            This chapter has examined various issues regarding antiretroviral treatment in the developing world, including international trade and patent laws, use of generic drugs, and arguments regarding drug resistance, patient adherence, cost-effectiveness, and prevention. Ultimately these concerns and the root of the issue surrounding HIV/AIDS treatment must consider the best quality of care for the millions of people currently living with HIV/AIDS and how best to prevent future infections. The future must continue to advocate for antiretroviral therapy in resource-limited settings and aim to find cost-effective, innovative ways to make HAART treatment a major part of international and national AIDS efforts. We must also look at effective preventive medical interventions (including vaccines and microbicides) and continue aggressively pushing prevention programs. Also the global community must address issues of growing poverty, political instability, and equity. Responses to these issues should be considered within a human rights framework.

            Finally, it is important to mention that issues regarding antiretroviral therapy in the developing world are consistently changing—changes in policies surrounding ARVs, trade and patent laws, developments in cost-effective care, etc. are emerging almost daily. Moreover, much of the information a year ago is now out-dated due to vast and swift changes within the field. Thus, the following websites are interesting resources to gain up-to-date information about new developments surrounding antiretroviral treatment in the developing world.

 

 

AIDS Related Information Sources:

 

Accelerating Access Initiative

www.unaids.org/acc_access/

 

Debt, AIDS, Trade, Africa

www.data.org

 

Doctors Without Borders: Access to Essential Medicines

www.accessmed-msf.org

 

 

The Global Fund

www.theglobalfund.org

 

UNAIDS

www.unaids.org

 

World Health Organization Three by Five Initiative

www.who.int/3by5/en

 

News Sources

The New York Times Online

www.nyt.com

 

BBC News AIDS Page

http://news.bbc.co.uk/2/hi/talking_point/special/aids/default.stm

 

The Lancet

www.thelancet.com

 

 

 

 



[1] WHO and UNAIDS (2003). Treating 3 Million by 2005: Making it happen, WHO

UNAIDS. 2003.

[2] Essex, M. and S. Mboup (2002). Introduction: The Etiology of AIDS. AIDS in Africa Second Edition. M. Essex, S. Mboup, P. J. Kanki, R. G. Marlink and S. D. Tlou. New York, Kluwer Academic/ Plenum Publishers: 1-10.

[3] HIV is a retrovirus characterized by a latency period prior to attacking an individual’s immune cells and antibodies. See footnote 1.

[4] UNAIDS (2003). AIDS epidemic update. Geneva, UNAIDS, WHO: 1-39, UNFPA (2003). State of World Population 2003 Making 1 billion count: Investing in adolescents' health and rights. Geneva, United Nations Population Fund: 92.

[5] UNICEF, UNAIDS, et al. (2002). Young People and HIV/AIDS Opportunity in Crisis. Geneva, UNICEF, UNAIDS, WHO: 1-48, OXFAM and IYP (2003). Highly Affected, Rarely Considered: The International Youth Parliament Commission's Report on the Impacts of Globalization on Young People. Sydney, International Youth Parliament and OXFAM: 169.

-UNAIDS (2003). See footnote 2.

[6] DATA (2004). Facts About... Debt, AIDS, Trade, Africa. 2004. http://www.data.org

-UNAIDS (2003). See footnote 2.

[7] UNAIDS (2002). Epidemiological Fact Sheets on HIV/AIDS and Sexually Transmitted Infections: Kenya, UNAIDS: 1-14.

[8] Weidle, P. J., T. D. Mastro, et al. (2002). "HIV/AIDS treatment and HIV vaccines for Africa." The Lancet 359: 2261-2267.

[9] MSF (2004). HIV/AIDS, Medecins Sans Frontieres. 2004.

[10] Even though ART and HAART are defined by triple therapy recent publications primarily specify triple-drug combinations as HAART. Based on current usage this chapter will also refer to HAART.

[11] Amoroso, A., C. E. Davis, et al. (2002). Antiretroviral Therapy in Resource-Limited Settings. AIDS in Africa Second Edition. M. Essex, S. Mboup, P. J. Kanki, R. G. Marlink and S. D. Tlou. New York, Kluwer Academic/ Plenum Publishers: 322-344.

[12] Amoroso et al. (2002). See footnote 2.

[13] Amoroso et al. (2002). See footnote 2.

[14] IRIN (2003). Global: WHO announces approval of generic antiretrovirals, UN Office for the Coordination of Humanitarian Affairs. 2004. http://www.irinnews.org/report.asp?ReportID=38166&SelectRegion=Global

[15] MSF (2004). 2 Pills a day saving lives, Medecins Sans Frontieres. 2004.

[16] IRIN (2003). See footnote 5

[17] Treatment Action Campaign is a South African grassroots organization, whose objectives are to “1. Ensure access to affordable and quality treatment for people with HIV/AIDS. 2. Prevent and eliminate new HIV infections. 3. Improve the affordability and quality of health-care access for all.” More information about this organization can be found at: http://www.tac.org.za/

[18] Doctors Without Borders launched a campaign advocating for access to essential treatments worldwide. More on this campaign and related information regarding AIDS drug treatments, as well as images of interesting educational posters, can be found at: http://www.accessmed-msf.org/index.asp

[19] Doctors Without Borders (2003). Trading Away Health. New York, Doctors Without Borders: 1-12.

[20] Gunaratnam, P. (2003). HIV/AIDS Prevention, Treatment and Care For Yougn People. In Highly Affected, Rarely Considered: The International Youth Parliament Commission's Report on the Impacts of Globalization on Young People. Sydney, OXFAM

International Youth Parliament: 45-57.

[21] Vaz, M. (2003). "Brazil offers expertise and support to Africa." The Lancet 362: 215.

[22] It is important to note that Cipla has been one of the driving forces behind the decline of ARV prices.

[23] Sharma, D. C. (2003). "ARV prices nosedive after Clinton brokering." The Lancet 362: 1467.

[24] Amoroso et al. (2002). See footnote 2.

-Marseille, E., P. B. Hoffmann, et al. (2002). "HIV Prevention before HAART in sub-Saharan Africa." Ibid. 359: 1851-1856.

-Weidle, P. J., T. D. Mastro, et al. (2002). "HIV/AIDS treatment and HIV vaccines for Africa." The Lancet 359: 2261-2267.

[25] Taegtmeyer, M. and K. Chebet (2002). "Overcoming challenges to the implementation of antiretroviral therapy in Kenya." The Lancet Infectious Diseases 2: 51-53, Liechty, C. A. and D. R. Bangsberg (2003). "Doubts about DOT: antiretroviral therapy for resource-poor countries." AIDS 17(9): 1383-1387.

[26] Hanson, S. (2002). "AIDS control in sub-Saharan Africa-- are more drugs and money the solution?" The Lancet Infectious Diseases 2: 71-72.

-Marseille, E. et al. (2002). See footnote 8.

[27] Pill burden refers to the number of pills patients are required to take. Considering ART or triple therapy requires taking three pills multiple times a day it is reported that patients may not stick to the treatment due to the burden of taking multiple medications, multiple times a day.

[28] Binswanger, H. P. (2003). "Willingness to pay for AIDS treatment: myths and realities." The Lancet 362: 1152-1153. pg. 1153

[29] Liechty, C. et al. (2002). See footnote 9. pg. 1384.

[30] Taegtmeyer and Chebet (2002). See footnote 9.

-Amoroso et al. (2002). See footnote 2.

[31] Weidle, P.J. et al. (2002), See footnote 8.

[32] Amoroso et al. (2002) See footnote 2.

[33] Hanson, S. (2002). See footnote 10. pg. 71.

[34] Kallings, L. O. and S. Vella (2001). "Access to HIV/AIDS Care and Treatment in the South of the World." AIDS 15(7): IAS1-IAS3.

[35] Creese, A., K. Floyd, et al. (2002). "Cost-effectiveness of HIV/AIDS interventions in Africa: a systematic review of the evidence." The Lancet 359: 1635-1642.

-Marseille, E. et al. (2002). See footnote 8.

-Lush, L. (2002). The International Effort for Anti-Retrovirals: Politics or Public Health? The Economics of Essential Medicines. B. Granville. London, Royal Institute of International Affairs: 232-241.

[36] Marseille, E. et al. (2002) pg. 1853.

[37] Lush, L. (2002). See footnote 19. pg. 238

[38] Lush, L. (2002). Pg. 240

[39] Liechty, C. et al. (2002). See footnote 9.

[40] Marseille, E. et al. (2002). See footnote 8.

-Weidle, P.J. et al. (2002). See footnote 8.

[41] Marseille, E. et al. (2002)

[42] Marseille, E. et al. (2002). Pg. 1855

[43] Marseille, E. et. al. (2002). Pg. 1855

[44] Farmer, P., F. Leandre, et al. (2001). "Community-base approaches to HIV treatment in resource-poor settings." The Lancet 358: 404-409, Laurent, C., N. Diakhate, et al. (2002). "The Senegalese government's highly active antiretroviral therapy initiative: an 18 month follow-up study." AIDS 16(10): 1363-1370, Weidle, P. J., S. Malamba, et al. (2002). "Assessment of a pilot antiretroviral drug therapy programme in Uganda: patients' responses, survival, and drug resistance." The Lancet 360: July 6.

[45] Laurent, C. et al. (2002). See footnote 26.

[46] Laurent, C. et al. (2002). Pg. 1369.

[47] Weidle, P. J. et al. (2002b). See footnote 26.

[48] Liechty, C. et al. (2002). See footnote 9.

[49] McNeil, D. G. (2003). Africans Outdo U.S. Patients in Following AIDS Therapy. The New York Times. New York.

[50] Liechty, C. et al. (2002). See footnote 9.

[51] Liechty, C. et al. (2002)

[52] Farmer et al. (2001).

[53] Ashraf, H. (2003). "Economists tell scientists AIDS drug projects can be scaled up." The Lancet 362: 215. pg. 215

[54] Farmer, P., F. Leandre, et al. (2001). "Community-base approaches to HIV treatment in resource-poor settings." Ibid. 358: 404-409. See footnote 26. pg. 407.

[55] Piot, P., D. Zewdie, et al. (2002). "Correspondence: HIV/AIDS prevention and treatment." Ibid. 360: 86.

[56] Liechty, C. et al. (2002). See footnote 9.

-Farmer, P. et al. (2001). See footnote 36.

[57] Farmer et al. (2001).

[58] Piot, P. et al. (2002).

[59] Binswanger, H. P. (2003). "Willingness to pay for AIDS treatment: myths and realities." The Lancet 362: 1152-1153.

[60] Ashraf, H. (2003). Pg. 215

[61] Ashraf, H. (2003).

[62] Doctors Without Borders. (2003).

[63] Galvao, Jane. 2004. Access to antiretrovirals: where South Africa, China, and Brazil meet. The Lancet. 363: 493

[64] Farmer et al. (2001)

[65] UNAIDS (2003).

[66] Mukherjee, J. S. (2003). "HIV-1 care in resource-poor settings: a view from Haiti." The Lancet 362(9388): 994-995.

[67] Farmer et al. (2001)

[68] Farmer et al. (2001) pg. 405

[69] At the time the article by Nierengarten was published in 2003, patient mortality had been reduced to 0%. You can learn more about this community-based initiative by visiting the Partners in Health website at http://www.pih.org.

[70] Farmer et al. (2001)

-Nierengarten, M.-B. (2003). "Haiti's HIV equity initiative." The Lancet Infectious Diseases.

[71] Mukherjee, J. S. (2003). "HIV-1 care in resource-poor settings: a view from Haiti." The Lancet 362(9388): 994-995.