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The immense burden of HIV disease in sub-Saharan Africa has focused international interest on HIV care, especially on the lack of access to antiretroviral therapy (ART).
Difficulties in implementing ART in Africa include drug costs, adequate long-term funding sources, assurance of drug quality, and rapid development of the human resources and healthcare infrastructure needed to deliver ART.
Important questions requiring study are the minimum level of laboratory monitoring and clinical support consistent with good treatment outcomes, the impact of antiretroviral drug resistance on treated individuals and communities, and the effect of ART on transmission at a community level.
There are some concerns and risks. First, a focus on treatment could compromise the commitment of individuals to risk-reduction, and of governments to prevention. Second, health equity could be reduced, by diverting scarce public funds from basic care for the poorest, to costly disease-suppressive care for a small and probably elite group.
In conclusion, while prevention must be the first priority, care is also essential. The vast prevailing economic inequity between the world's rich and poor is the fundamental determinant of inequities in health and healthcare, including care for HIV. The global community of healthcare workers must focus its substantial influence on changing political and economic policies that foster injustice and AIDS.
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The immense burden of HIV infection in Africa demands better care for those already infected, as well as better prevention for those who are not infected. Having witnessed the benefits of antiretroviral therapy (ART) in industrialized countries, many individuals and organizations have begun to question why this treatment is not available to the millions of HIV-infected patients in Africa. Recent large reductions in the price of proprietary, and emerging generic antiretroviral drugs have raised hopes that wider use in Africa might be feasible.
The disparity in access to HIV treatment between the world's rich and poor is self-evidently unjust. This injustice provides a powerful argument for expanded provision of ART in Africa. However, this injustice is neither new, nor specific to HIV care. It has long characterized access to basic healthcare (the difference in annual per capita health spending between the world's richest and poorest countries now approaches 1000-fold), and to basic human needs such as food, clean water, shelter, and education in Africa. Moreover, this inequality is steadily worsening.1
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Costs of antiretroviral therapy have dropped over a very short period, from US$10-12,000 per year, to as low as US$320 per year for the lowest-cost combination antiretroviral regimen from a generic manufacturer.2 These figures may now be approaching the cost of production. While these price reductions are remarkable and encouraging, the cost of ART remains far beyond the reach of the majority of Africans. Even at the lowest foreseeable prices, per patient cost of the drugs is many times greater than the per capita health spending of any poor country, and greater than per capita income in the poorest countries. In populations where more than one in four are HIV-infected, total national drug costs would be immense in relation to locally available resources.
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Support from aid agencies, nongovernmental organizations, or industry donors may play a useful role in pilot projects or in supporting specific aspects of an ART program. However, neither the carefully calculated generosity of the pharmaceutical industry, nor the usually short attention span of Western donors is likely to prove a reliable foundation for a program of the necessary scale and duration. The United Nations has recently announced a program of increased support against the major disease killers in resource-poor countries, including HIV. Even if their funding target were to be reached and sustained, the proposed amount is not sufficient to meet both treatment, and other HIV-related needs such as basic health infrastructure and HIV vaccine development.3 There are also serious reservations about the proportion of aid funding for the poorest countries that would effectively be paid directly to the international pharmaceutical industry.4
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Due to the high cost of ART and the limited resources available for health in Africa, paying for ART from the public healthcare budget would necessitate major cuts elsewhere in HIV prevention, primary care, or some other area of government services. By way of analogy, development advocate, David Morley, used to rail against developing countries spending a large proportion of their resources on national hospitals that effectively served only a small minority of the population. He pointed out that such hospitals were ultimately responsible for the deaths of large numbers of children whose lives could have been saved by the wiser and more equitable use of resources.5 In the case of ART, the poor majority would lose most from cutbacks in basic services, while members of a small, better off and well-connected urban elite would be most likely to benefit from an ART program. In many African countries today, diversion of large sums of public money to ART could very easily result in a net negative impact on population health, and an undesirable decrease in health equity.
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Given the obstacles confronting the provision of ART to millions, it is sometimes suggested that treating even a small number of people would help a little. But since one of the ethical imperatives to treatment is the large scale of illness and death caused by HIV, a realistic expectation of reaching some substantial proportion of HIV-infected individuals in the community is necessary in order to justify the introduction of ART. From a public health perspective, the scale of the intervention should be sufficient to result in a measurable population impact. If, as seems likely in the immediate future, treatment were available for only a minority, the processes of determining criteria for treatment and selecting treatment candidates would challenge the most cohesive and organized society.
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It has been argued that ART would be supported from entirely new funding sources. "New money," like free lunch, has to be viewed with skepticism. Until there is a dramatic and sustained change in the level of commitment of donor countries, external funding for ART can only come at the expense of other programs such as vaccination initiatives. Over the past decade, the proportion of gross domestic product, directed by wealthy countries to foreign aid, has been declining steadily, rather than increasing.6
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African countries, in which HIV is now endemic, continue to face the daunting challenge of distributing limited resources among the many competing needs within their health sectors. They must ask how many lives could be saved by investing US$320, multiplied by some thousands of patients treated with ART, in immunization, malaria control, the tuberculosis (TB) program, HIV prevention, or primary education.
Consider a hypothetical, but all-too-typical, African family in a setting where ART was widely introduced in the absence of broader economic and social changes. A father with symptomatic HIV infection receives treatment that costs at least US$320 annually. His wife has TB for which adequate diagnosis and treatment are not available in their community. His two youngest children are malnourished and suffer from recurrent malaria. One child has died of pneumonia, for which basic care was unavailable, and the family cannot afford primary school fees. Even when he is well, the father's annual income is less than US$320. The annual cost of disease suppressive treatment for one person could have met most or all of the whole family's basic nutritional and educational needs, and paid for life-saving TB and pneumonia treatment. The father might even consider trading his medication to feed his family. What are the health spending priorities in this family, this community, this country?
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Prevention of mother-to-child transmission (MTCT) would be a more efficient, and immediately feasible use of antiretroviral drugs than therapy. The amount of drug required is orders of magnitude smaller, and the benefit of preventing infection is qualitatively different from that of suppressing it.
Even so, there are a number of reasons MCTC prevention in resource-poor countries remains almost entirely limited to small pilot projects. The ultimate preventive benefit of the low-cost regimens after follow-up through the period of breast-feeding, has been modest. There was 15 percent transmission at follow-up to18 months after delivery in the Ugandan nevirapine study.7 Prerequisites for implementation of MTCT prevention, which are currently lacking in many African settings, are a greatly strengthened obstetrical care system; acceptance of testing by women, their partners, and communities; widely available, accurate serologic testing; adequate qualified staff for counseling and testing; and assured procurement and distribution of antiretroviral drugs. The children whose lives are saved by this intervention are almost all at markedly increased risk of the nutritional, educational, and survival hazards of being orphaned in Africa, so that MTCT prevention programs need to be accompanied by enhanced supports for them. Finally, the difficulties of stopping the mother's therapy as soon as the child is born, and of treating only one member of the family, may also prove a challenge for MTCT programs in some communities.
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Aside from the purchase cost of antiretroviral drugs, there are also daunting problems posed by procurement, distribution, and management. A relevant parallel for many African countries is the national tuberculosis program. Tuberculosis treatment is completed in six months, the drugs cost less than US$10 per course, and the annual number of patients in Zimbabwe is 50,000. In contrast, ART requires indefinite treatment, the drugs cost at least US$320 per year, and a conservative estimate of ART candidates is 250,000 among 1.5 million HIV-infected people. Yet many countries in Africa, including Zimbabwe, are struggling to meet the human and material resource needs and organizational requirements of their TB programs. In other areas of many African healthcare systems, basic and inexpensive drugs are often "out of stock" due to shortage of management capacity, limited funds, and occasionally, theft or fraud. The risk of theft or fraud would be multiplied many times by the introduction of antiretroviral agents with their very high monetary value, into the drug distribution systems of very poor countries.
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The striking benefits observed with ART in Western countries were obtained in treatment programs incorporating frequent viral load and CD4 cell count monitoring which has been considered an essential element of therapy.8 The cost and logistic requirements of these investigations comprise a major obstacle to the implementation of ART in sub-Saharan Africa. It has been proposed that most of the benefits of ART might be realized without them. This is an exciting, but unproven hypothesis. Studies to evaluate the efficacy of this strategy, and to determine the practical details of implementation will be necessary before large-scale programs can be based on it.
In TB treatment programs, practical and operational details, and program quality make the difference between success of greater than 95 percent in the best programs, versus cure rates as low as 11 percent.9 Similarly, in treatment of HIV infection, how treatment is delivered makes all the difference. Specially qualified doctors and nurses with multidisciplinary teams support adherence, manage adverse effects, address complex drug interactions, and provide other types of medical and psychosocial support in many "Western" HIV clinics. How much of this can we do without? At present, there is very little evidence to indicate how ART might be provided on a large scale in Africa, or to predict the likely magnitude or sustainability of benefits achievable under "field conditions" there.
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Another lesson from the TB experience is the need for routine assessment of drug quality and bioavailability, especially when new suppliers are used.10-12 The quality of drugs available in many low-income countries has been found to be highly inconsistent, particularly in the case of more complex products such as fixed-dose combination tablets for TB.13
The manufacture of some antiretroviral drugs is complex, and for some agents, the formulation is critical to adequate absorption. With current ART, there is very little "margin for error," so that relatively small reductions in bioavailability could lead to treatment failure and drug resistance. Bioequivalence studies on the generic products, proposed for use in ART programs, are not yet widely available.
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We are still at an early stage in our understanding of antiretroviral resistance in terms of how to measure it, its transmission, and particularly, its long-term population impact. In the United Kingdom, where most treatment has been delivered with frequent laboratory monitoring and expert supervision, 27 percent of newly diagnosed cases of HIV have laboratory evidence of key mutations associated with drug resistance, after about five years of population exposure to combination ART.14 Clinics in industrialized countries encounter increasing numbers of patients who are difficult to treat because of drug resistance. In low-income countries, resistance could lead to individual treatment failure, compromise a patient's future treatment options, limit the efficacy of community treatment programs, and even compromise the most cost-effective use of antiretroviral drugs such as prevention of mother-to-child transmission. The disastrous impact of multiple drug resistance in TB should prompt serious concerns about the potential for development of resistance in any ART program.
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It has been argued that the promise or hope of ART is needed to "Break the Silence" that stifles community response to HIV in southern Africa. While this is an attractive hypothesis, it is supported by few precedents. The major successes in HIV prevention, in Western gay men,15 Thai commercial sex workers and their clients,16,17 young women in Uganda,18 and others were achieved in the absence of access to ART. On the other hand, there are reports from Western countries,19,20 and anecdotal indications from Africa, suggesting that the perceived availability of effective treatment can reduce uptake of the prevention messages so vital to any effective response to the HIV epidemic. There is widespread concern that a focus on treatment may distract governments from the necessary commitment to HIV prevention—the natural tendency for clinical care to trump public health when spending decisions are made, is all the more likely to manifest in the context of an issue as emotive as ART.
Ultimately, acceptance of the premise that prevention is dependent on access to ART, implies an alarmingly defeatist attitude in respect to the prevention measures which are both essential and possible. Experience in many populations, including some in Africa, firmly contradicts the assertion that "we still have no good evidence that primary prevention works."21
Prevention is still the first priority. While there are 1.5 million Zimbabweans living with HIV infection, there are 6 million under the age of 15, of whom UNAIDS predicts that fewer than 30 percent will survive free of HIV infection, unless we dramatically improve our commitment to effective prevention measures.
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It has been hypothesized, extrapolating from observational studies,22 that ART might reduce HIV transmission by lowering viral loads.23 However, the proposed use of ART in Africa would involve initiation of treatment at a relatively late, symptomatic stage of infection so that treatment would be likely to affect only a small part of an individual's total lifetime transmission potential. A further concern is that modest negative changes in risk behaviour would overwhelm any positive effects from viral load reduction.24
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We must provide care for people with HIV infection for basic humanitarian reasons, and because fundamental principles of healthcare ethics demand no less. Moreover, while much is made of a conflict between care and prevention, the two are inextricably intertwined. Refusal of care would reinforce the stigma of HIV, adding greatly to the obstacles facing prevention.
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These cautions in regard to ART do not constitute a reason for inaction, but a call to action on a broader front. With the increased profile currently given to HIV by the press, the United Nations, and others, we have an opportunity that we cannot afford to miss, to reassess and reinvigorate global, national, and community responses to the HIV epidemic. Such a comprehensive response must include strong political leadership, open public discussion, commitment on a large scale to prevention of sexual transmission, systematic strengthening of prevention and treatment of sexually transmitted disease, and development of comprehensive programs for prevention of mother-to-child transmission. Other immediate priorities are enhanced basic medical and symptomatic care of people with advanced disease, and management of opportunistic infections, especially TB. A number of critical questions require rigorous scientific investigation that must involve creative collaboration between communities, healthcare workers, and scientists of North and South.
HIV and its treatment confront us with the human impact of the intolerable current levels of global disparity. We need to ensure that efforts to obtain drugs for one disease, however important it may be, do not detract from awareness of the enormous inequality that underlies Africa's health crisis. No drugs, however good or cheap, will cure the virus of inequity infecting the industrialized world's relations with Africa. Progress in remedying the structural causes of disparity, such as the insupportable debt burden and discriminatory trade rules, is essential to real, sustainable advances in health, including access to treatment for HIV.
This is a new field of advocacy and action for health workers, but it is where we belong. In addressing the twin problems of disease and inequality, members of the global community of healthcare workers are natural leaders, with the knowledge, credibility, and resources to influence public opinion and political decisions at an international level.
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I owe a debt of gratitude to Walter Kipp, MD, MPH, PhD, and Adam Houston who provided valuable insight, suggestions and criticism, and to Janet McDonald who carefully prepared the manuscript.
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1. Benatar S. Respiratory Health in a Globalizing World. Am Rev Resp Crit Care Med 2001; 167:1064-7.
2. McGreal C. Nigeria to import HIV drugs on the cheap. The Guardian Weekly 13-19/12/2001; 165(25):1.
3. Anon. A global health fund: heeding Koch's caution. Lancet 2001 Jul 7;358(9275):1.
4. Ford N, ‘t Hoen E. The Global Health Fund: moral imperative or industry subsidy? Lancet 2001 Aug 18;358(9281):578.
5. Morley D. Paediatric priorities in evolving community programmes for developing countries. Lancet 1976 Nov 6;2(7993):1012-4.
6. The World Bank Group. Making international aid and debt relief more effective. Global Development Finance Vol. 1 Chapter 4. Online at http://www.worldbank.org/prospects/gdf2001/CH4--84-107.pdf. Accessed December 30, 2001.
7. Eshleman SH, Mracna M, Guay LA, Deseyve M, Cunningham S et al. Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET 012). AIDS 2001 Oct 19;15(15):1951-7.
8. Haubrich RH, Currier JS, Forthal DN et al. A randomised study of the utility of Human Immunodeficiency Virus RNA measurement for the management of antiretroviral therapy. Clin Infect Dis 2001 Oct 1;33(7):1060-8.
9. Brudney K, Dobkin J. Resurgent tuberculosis in New York City: HIV, homelessness and the decline of TB control program. Am Rev Respir Dis 1991 Oct;144(4):745-9.
10. International Union Against Tuberculosis and Lung Disease, World Health Organization. Assuring bioavailability of fixed-dose combinations of anti-tuberculosis medications. Int J Tuberc Lung Dis 1999 Nov;3(11 Suppl 3):S282-3.
11. Laserson KF, Kenyon AS, Kenyon TA, Layloff T, Binkin NJ. Substandard tuberculosis drugs on the global market and their simple detection. Int J Tuberc Lung Dis 2001 May;5(5):448-54.
12. Pillai G, Fourie PB, Padayatchi N, et al. Recent bioequivalence studies on fixed-dose combination anti-tuberculosis drug formulations available on the global market. Int J Tuberc Lung Dis 1999 Nov;3(11 Suppl 3):S309-16; discussion S317-21.
13. Taylor RB, Shakoor O, Behrens RH, et al. Pharmacopoeial quality of drugs supplied by Nigerian pharmacies. Lancet 2001 Jun 16;357(9272):1933-6.
14. UK Collaborative Group on Monitoring the Transmission of HIV Drug Resistance. Analysis of prevalence of HIV-1 drug resistance in primary infections in the United Kingdom. BMJ 2001 May 5;322(7294):1087-8.
15. Ekstrand M. Safer sex maintenance among gay men: are we making any progress? AIDS 1992 Aug;6(8):875-7.
16. Nelson K, Celentano D, Eiumtrakol S, et al. Changes in sexual behavior and a decline in HIV infection among young men in Thailand. N Engl J Med 1996 Aug 1;335(5):297-303.
17. Celentano D, Nelson K, Lyles C, et al. Decreasing incidence of HIV and sexually transmitted diseases in young Thai men: evidence for success of the HIV/AIDS control and prevention program. AIDS 1998 Mar 26;12(5):F29-36.
18. Kilian A, Gregson S, Ndyanabangi B, et al. Reductions in risk behavior provide the most consistent explanation for declining HIV-1 prevalence in Uganda. AIDS 1999 Feb 25;13(3):391-8.
19. Scheer S, Chu PL, Klausner JD, Katz MH, Schwarcz SK. Effect of highly active antiretroviral therapy on diagnoses of sexually transmitted diseases in people with AIDS. Lancet 2001 Feb 10;357(9254):432-5.
20. Dukers NH, Goudsmit J, de Wit JB, Prins M, Weverling G-J, Coutinho RA. Sexual risk behaviour relates to the virological and immunological improvements during highly active antiretroviral therapy in HIV-1 infection. AIDS 2001 Feb 16;15(3):369-78.
21. Farmer P, Léandre F, Mukherjee JS, et al. Community-based approaches to HIV treatment in resource-poor settings. Lancet 2001 Aug 4;358(9279):404-9.
22. Gray RH, Wawer MJ, Brookmeyer R, et al. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet 2001 Apr 14;357(9263):1149-53.
23. Berkman A. Confronting global AIDS: prevention and treatment. Am J Public Health 2001 Sep;91(9):1348-9>.
24. Law MG, Prestage G, Grulich A, Van de Ven P, Kippax S. Modelling the effect of combination antiretroviral treatments on HIV incidence. AIDS 2001 Jul 6;15(10):1287-94.
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A consensus statement by organizations delivering AIDS projects for the Canadian International Development Agency (CIDA). The opportunities and challenges of introducing anti-retroviral therapy (ART) in resource-poor settings. Online at http://www.cpha.ca/english/policy/pstatem/ART/artintro.htm. ART_consensus.pdf.
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