E-DRUG: BMJ on ARV rollout, Malawi experience
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[Editorial and interesting article on ARV rollout and TB DOTS; copied as fair use; WB]
http://bmj.bmjjournals.com/cgi/content/full/329/7475/1118
BMJ Editorial 13 Nov 2004
Highly active antiretroviral therapy
We need to scale up its use and reach with existing facilities in poor countries
The barriers to providing highly active antiretroviral therapy (HAART) in poor countries have until recently seemed insurmountable. The cited problems have ranged from weak health systems and poor infrastructure to inadequate numbers of health professionals. In reality, the main barrier has been the very high cost of antiretroviral drugs. Current increase in access to HAART has resulted from cuts in the price of antiretroviral drugs and increased funding by international bodies, notably the Global AIDS Fund, the World Bank, and the President Bush Emergency Program for AIDS Relief.
Africa's grim AIDS data include 25 million people living with HIV and 2.2 million dead in 2003 alone.1 The challenge now is to move quickly from small town or community specific projects to provide nationwide high quality, equitable, and sustainable programmes. Valuable lessons have been learned from pilot programmes in poor countries, including the Malawi experience described in this issue, but individually these do not provide a blueprint for universally applicable scale-up models (p 1163).2 However, if the cumulative knowledge from these programmes is applied with tactical adjustment tailored to the local conditions it should be sufficient for programmes to proceed, without the need for new pilot studies, which would be unethical if they deny or delay the provision of life saving treatment to patients.
The dreaded risk associated with scaling up HAART is the development of widespread drug resistance secondary to drug misuse,3 which in the long term may render the cheap first line antiretroviral drugs ineffective. Although initial data indicate good adherence4 and treatment outcomes in Africa, it is critical to enforce and maintain strong adherence strategies, as it is the key to success in controlling the carnage caused by HIV/AIDS.
Tuberculosis control practices
Recommendations to accelerate quality HAART programmes include the application of best tuberculosis control practices, especially direct observation of treatment strategy. Additionally, the dangerous HIV-tuberculosis coinfection, described as "a collaboration to kill," supports calls for collaborative interventions. Since up to 75% of patients with tuberculosis are coinfected with HIV, joint interventions, including voluntary counselling and testing, and tuberculosis diagnostics are vital for effective management of the two diseases.5
Unlike tuberculosis, however, HIV is a lifetime illness with different modes of transmission and a much higher stigma. Furthermore, because such huge numbers are infected, strategies used against tuberculosis are not always appropriate or sufficient for HIV and may need tactical modification. Paul Farmer's team in rural Haiti has successfully shown that people who accompany peasants can be partners for effective antiretroviral therapy. The accompanying persons are recruited from within the community, to supervise and provide HAART directly observed therapy, short course.6 Other variants of DOTS have used patients' confidantsmainly friends, relatives, or neighboursto fill the staffing gap in counselling and follow up of patients.
Brazil's successful universal AIDS treatment programme initially started by using mainly clinical monitoring based on recommendations from the World Health Organization and the US Centers for Disease Control and Prevention, and simple laboratory tests, then progressively built capacity over time.7 This experience shows that HAART scale up in other poor and medium income countries can proceed expeditiously, using whatever facilities are available, while systematically building capacity, including training healthcare providers, establishing laboratories, drugs supply logistics, and monitoring and evaluation tools. Mobile clinics may be used successfully to take services to hard to reach populations.
Stepwise strategy
We need to plan and draw together a stepwise strategy that incorporates other AIDS interventions, including prevention of transmission from mother to child, voluntary counselling, and testing as well as other preventive strategies, such as distribution of condoms, into a comprehensive programme that will ultimately integrate into an improved robust national healthcare system.
In developing countries, most public healthcare facilities are crammed with AIDS patients over and above other rampant endemic diseases, including opportunistic infections and malaria. Healthcare providers are overworked and poorly paid; some are themselves sick or have seen colleagues die.8 They need to be supported and motivated to carry out their tasks by incentives such as improved remuneration, better working conditions, and access to treatment.9 To expect to set up a successful AIDS treatment programme is unrealistic if other vital health needs are ignored. New antiretroviral therapy facilities, including laboratories, need to benefit other health services, which serve patients and staff with other needs.
Staff shortages
The shortage of healthcare providers may be partly compensated for by training and involving community based organisations such as People Living With HIV/AIDS, which can provide the human resources to help with ongoing support and follow up of patients. As in all emergencies, imaginative problem solving should be encouraged. For example, the Joint Clinical Research Centre's AIDS clinic in Uganda once ran short of space because of a sudden surge of patients as a result of the lowering of the price of HAART. Pitching tents alleviated the problem. The practice has been applied successfully to other deficient facilities while funds are being sought for more permanent arrangements.
In the absence of a fully replicable universal scale up model to deliver HAART, a hybrid approach that takes into account the diversity within and between countries is the most practical way forward. And for them to be sustained programmes must be planned, led, implemented, managed, and owned by host countries or carried with their full participation.
Continued advocacy for affordable drugs and monitoring laboratory tests and better patent laws to allow access to lower cost quality generics are needed along with focused international support. But in the long term, the only the way for poor countries to ensure that they become self sustainable in dealing with HIV/AIDS and other future disasters is for them to establish good governance and policies that promote social economic development to lift them out of the poverty trap.
Peter Mugyenyi, director
Joint Clinical Research Centre, 1 Ring Road, Mengo, PO Box 10005, Kampala, Uganda (pmugyenyi@yahoo.co.uk)
Competing interests: None declared.
References
1. World HIV and AIDS Statistics Including Deaths: UNAIDS 2004 report on global AIDS epidemic. www.avert.org/worldstats.htm (accessed 22 Oct 04).
2.Harries AD, Libamba E, Schouten EJ, Mwansambo A, Salaniponi FM, Mpazanje R. Expanding antiretroviral therapy in Malawi: drawing on the country's experience with tuberculosis. BMJ 2004;329: 1163-6.[Free Full Text]
3.Adje C, Cheingsong R, Roels TH, Maurice C, Djomand G, Verbiest W, et al. High prevalence of genotypic and phenotypic hiv-1 drug-resistant strains among patients receiving antiretroviral treatment in Abidjan, Cote d'Ivoire. J Acquir Immune Defic Syndr 2001;26: 501-6.[ISI][Medline]
4. Oyugi JH, Byakika-Tusiime J, Charlebois ED, Kityo C, Mugerwa R, Mugyenyi P, et al. Multiple validated measures of adherence indicate high levels of adherence to generic hiv antiretroviral therapy in a resource-limited setting. J Acquir Immune Defic Syndr 2004;36: 1100-02.[Medline]
5. Joint UNAIDS WHO Press Release. Combining TB treatment with HIV testing and treatment. www.unaids.org/en/media/press+releases.asp (accessed 7 Oct 2004).
6. Farmer P, Leandre F, Mukherjee JS, Claude M, Nevil P, Smith-Fawzi MC, et al. Community based approaches to HIV treatment in resource-poor settings. Lancet 2001;358: 404-9.[CrossRef][ISI][Medline]
7. Schechter M. Expert commentary: Scaling up antiretroviral therapy for developing countrieswe can walk and chew gum at the same time. 2nd International Society Conference on HIV Pathogenesis and Treatment. 13-16 July 2003, Paris, France. www.impactaids.org.uk/med6.htm (accessed 28 Oct 2004).
8. Mpundu M. The burden of HIV/AIDS on the Zambian health system. AIDS Anal Afr 2000;10: 6.
9. Uebel K, Friedland G, Pawinski R, Holst H. HAART for hospital health care workers-an innovative programme. S Afr Med J 2004;94: 423-7.[Medline]
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[2nd article in same BMJ]
http://bmj.bmjjournals.com/cgi/content/full/329/7475/1163
Expanding antiretroviral therapy in Malawi: drawing on the country's experience with tuberculosis
Anthony D Harries, technical assistant in HIV care and support1, Edwin Libamba, head of unit1, Erik J Schouten, technical assistant in HIV/AIDS coordination1, Andrina Mwansambo, medical officer in HIV care and support4, Felix M Salaniponi, director2, Rex Mpazanje, director3
1 HIV/AIDS Unit, Ministry of Health, PO Box 30377, Lilongwe, Malawi, 2 National Tuberculosis Control Programme, Ministry of Health, Malawi, 3 Department of Clinical Services, Ministry of Health, Malawi, 4 National AIDS Commission, Lilongwe, Malawi
Correspondence to: A D Harries adharries@malawi.net
The DOTS ("directly observed treatment, short course") strategy has been successfully used in developing countries to provide effective control of tuberculosis. Field workers in Malawi are promoting the same approach for HIV infection through the expansion of highly active antiretroviral therapy
Highly active antiretroviral therapy (HAART) must be expanded in sub-Saharan Africa, where the HIV/AIDS epidemic is taking an appalling toll. Malawi, a small, poor African country, is expanding HAART nationally. The "directly observed treatment, short course" (DOTS) strategy has been successfully used for years to provide effective national control of tuberculosis, and the same concepts are being applied for delivering HAART. We describe how the principles of standardised case finding, standardised treatment regimens, regular monitoring and evaluation, and uninterrupted supplies of drugs can be used to deliver HAART. If implemented well, these principles should ensure a controlled delivery system, which would reduce the risks of inconsistent prescribing practices and the development of drug resistance.
Response to Malawi's HIV/AIDS epidemic
In 2003 sub-Saharan Africa had an estimated 3.4 million new cases of HIV infection and up to 2.4 million deaths.1 Malawi has one of the highest HIV/AIDS prevalence rates in sub-Saharan Africa, with 14% of those aged 15-49 years infected.2 In 2003 an estimated 900 000 people had HIV/AIDS and about 86 000 died from AIDS related illnesses. AIDS is killing young adults in their most productive years, retarding development, producing a huge orphan population, and creating the foundations for political instability.
HAART has dramatically improved the survival of patients with HIV/AIDS in developed countries,3 4 where AIDS is now regarded as a potentially treatable and chronic condition rather than a fatal disease. In Malawi 170 000 people are estimated to need HAART.2 A countrywide survey by the Ministry of Health, however, found that just over 4000 people had started on HAART in the public and private sectors in 2003 and about 5000 were taking the medications at the start of 2004.5 A fast track approach to expanding treatment is urgently needed.
Fast countrywide expansion of HAART
The World Health Organization in September 2003 declared the lack of access to HAART a global health emergency.6 The organisation called for ambitious and unprecedented action to ensure that by the end of 2005 at least three million people needing HAART in developing countries would have access to itthe so called "3 by 5" initiative. Malawi has developed a two year (2004-5) antiretroviral expansion plan, with the goal of delivering HAART to 80 000 eligible patients in the country by the end of 2005. The plan wants antiretroviral drugs to be supplied free to as many eligible patients as possible. It provides a detailed outline of how antiretrovirals will be made available in a total of 54 central, district, and mission hospitals in the country by December 2004.
Learning from tuberculosis control
The delivery of antiretrovirals, according to standards practised in developed countries, requires high levels of expertise and technology. Malawi is one of the world's poorest countries, with a huge human resources deficit and about $12 (#7; 10) per head of population spent annually on health.7 The country does not have the human or technological resources to offer many different HAART regimens to patients or the means to assess and monitor patients by measuring viral load and CD4 lymphocyte counts.
Through the efforts of organisations such as WHO and the International Union Against Tuberculosis and Lung Disease, DOTS (similarly demanding of expertise and technology in developed countries) has been administered to millions of patients with tuberculosis in poor countries.8 Malawi has run an effective DOTS tuberculosis control programme for 20 years, providing diagnosis by a simple algorithm based on sputum smear microscopy and treatment regimens recommended by WHO. A rigorous system of monitoring and evaluation enables information to be collected nationally on case finding and treatment outcome. Every year up to 27 000 patients access the treatment, with acceptable success rates.9
The Malawi tuberculosis control programme is run by paramedical staff; health assistants working as district tuberculosis officers and clinical officers working as regional tuberculosis officers provide supervisory and monitoring roles (figure). The key to success is standardisation. Every treatment facility operates in the same way, and all regional officers conduct supervision using the same tools and procedures. Tuberculosis treatment and HAART are both taken for a long time (eight months for tuberculosis, for life for HAART). The delivery of HAART has much to learn from the tuberculosis services,10 and we have developed a national plan to expand delivery of antiretrovirals.
[Omitted: picture, titled: District tuberculosis officers in Malawi help to implement the country's tuberculosis control programme]
Framework for delivering antiretrovirals
As for DOTS, we have developed a framework for delivering antiretrovirals that consists of a goal, specific objectives, a strategy, a policy package, key operations, and indicators (box 1) to measure progress with antiretroviral therapy. National guidelines for such treatment are available, and progress has already been made. At the moment there are 23 antiretroviral clinics in the public health sector delivering HAART, with the number scheduled to increase to 54 by the end of the year. So far, 375 healthcare workers in the public sector have been trained to use HAART, with the number expected to increase by an additional 100 by the end of 2004.
Eligibility criteria for treatments when resources are limited
The commonest type of tuberculosis in Malawi is pulmonary disease. The diagnostic algorithm stipulates that all people suspected of having pulmonary disease (defined as having a cough for three or more weeks) have sputum smears examined for the presence of acid-fast bacilli. Patients with acid-fast bacilli in their sputum are registered as smear positive for pulmonary disease, whereas those without are registered as smear negative pulmonary disease if they fulfil certain other criteria.11
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Box 1: Indicators to measure progress with delivery of antiretroviral drugs
Input indicators
A guidelines manual for delivering antiretroviral therapy
Number of HIV clinics administering such therapy
Number of staff trained and accredited in use of antiretroviral drugs
Antiretroviral drugs and HIV test kits always available in hospital pharmacies, and uninterrupted supplies of the drugs to patients
Output indicators
Number of patients who start on standardised antiretroviral therapy
Number of patients who are still aliveand still taking the therapyat a given time
Percentage of patients who show 95% adherence to the therapy
Percentage of patients having antiretroviral therapy who have returned to work
Number of new orphans registered each year in a district in which antiretroviral therapy is available
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This simple approach recognises the fact that mycobacterial culture is not feasible in peripheral units but that light microscopes and trained microscopy staff are available. In a similar vein, simple criteria have been developed for assessing eligibility for HAART. An essential criterion is a documented positive HIV serology test, ascertained by whole blood rapid tests for HIV-1 and HIV-2. Adult patients known to be HIV seropositive and who have understood the implications of antiretroviral therapy are eligible for HAART if they are assessed as being in clinical stages III or IV as classified by WHO,12 in clinical stage II with total lymphocyte count < 1200x106/l or have a CD4 count < 200x106/l. Most antiretroviral clinics will have no access to CD4 counts and will therefore start patients on therapy on the basis of clinical criteria. In staff training, the diagnosis of opportunistic infections and correct staging of disease are strongly emphasised.
Standardised antiretroviral therapy
Malawi has stipulated its first line, alternative first line, and second line HAART regimens (box 2). For rapid countrywide expansion, the country has adopted the first line regimen only, except in the few centres where expertise already exists in using HAART regimens.
This new approach simplifies the management of patients, the whole system of recording and reporting, and drug procurement and drug security. It is based on observational experience in three sites that 85-90% of patients do well on this regimen. Patients who develop side effects will either stop treatment or be referred to the centres with more experienced staff who can use alternative first line therapy. Once antiretroviral clinics have shown they are competent to deliver the first line regimen, they will be assessed for their readiness to deliver alternative first line and second line regimens according to the national treatment guidelines.
The approach is borrowed from the tuberculosis treatment model, where five essential first line tuberculosis drugs are used in slightly different combinations to treat different forms of the disease. No investment has been made in expensive, toxic, and difficult to manage second line drugs for treating multidrug resistant tuberculosis, which is rare in Malawi owing mainly to good management with first line therapy.13
Good drug adherence and compliance with the treatment regimen are two essential components for successful treatment with either DOTS or HAART. In Malawi, guardians (spouses, members of the extended family, or sometimes children) have been used for several years to help patients with adherence and compliance with DOTS.14 15 The same principles are being applied to HAART. While evidence is growing that this may be a useful approach,16 not everyone is enthusiastic about its applicability.17
Registration, recording, and reporting
One of the important elements in preventing multidrug resistant tuberculosis is an uninterrupted supply of drugs. The number of cases registered nationally for treatment in the previous two quarters allows for realistic, six monthly procurement orders. (The number of cases is obtained from tuberculosis registers into which district tuberculosis officers enter the details of every patient registered for treatment.) The data in these registers are collated into quarterly reports on case finding, which in turn are put together into national reports. Standardised treatment outcomes of patients in these quarterly cohorts are also regularly evaluated using patient treatment cards, with reports on cure, death, default, and transfer-out being provided at treatment facilities and also nationally. The system is well tried, with no drug interruptions for years in Malawi and with regular reports on treatment outcome.
Malawi has adopted a similar system for monitoring antiretroviral therapy. Antiretroviral registers, patient master cards and forms for quarterly cohort analysis have already been used successfully in certain districts. The routinely collected data should allow regular, up to date information to be collected nationally on variables such as the number of patients ever started on HAART, the number alive, and the percentage of patients back in employment.
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Box 2: Antiretroviral therapy regimens in Malawi
First line regimen
Stavudine plus lamivudine plus nevirapine
Alternative first line regimens in cases of adverse side effects
With severe peripheral neuropathy due to stavudineuse zidovudine plus lamivudine plus nevirapine
With hepatitis due to nevirapineuse stavudine plus lamivudine plus efavirenz
Severe skin reactions due to nevirapineuse stavudine plus lamivudine plus efavirenz
Second line regimen in the event of failure of first line regimen
Zidovudine plus didanosine plus nelfinavir
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Summary points
The DOTS ("directly observed treatment, short course") strategy for tuberculosis control is of proved effectiveness in resource poor countries
Expanding highly active antiretroviral therapy (HAART) in countries such as Malawi may be achieved using the same principles as for tuberculosis control programmes
These include the adoption of standard criteria for starting treatment and a reliable system for registering and monitoring cases and evaluating treatment outcomes
Conclusion
Expanding HAART in resource poor countries will be a major challenge. Even if the technical difficulties of delivering treatment can be solved, there is the additional problem of scarcity of skilled human resources, particularly in sub-Saharan Africa. In May 2004 Malawi launched a national in-service antiretroviral training programme, and five months later it had trained 375 medical officers, clinical officers, and nurses in antiretroviral management at a total cost of $85 000. With funds from WHO and the Global Fund against AIDS, Tuberculosis and Malaria, it plans to continue regular in-service training on HAART as well as integrating this topic into the undergraduate curriculum at the schools of medicine, health sciences, and nursing. Parallel to these attempts to increase the number of health workers able to manage HAART is an urgent need to tackle the national crisis in human resources, by producing more clinicians and nurses from training institutions and to retain those entering the service. The number of patients on HAART will after a few years far exceed those receiving tuberculosis treatment, and the human resource equation will be vital in determining success or failure of this intervention.
Some argue that rapid expansion in such an environment is fraught with danger and that HAART should rather be introduced in controlled settings through research programmes and improved infrastructure.18 This view ignores, however, the scale of the problem and the urgent need to provide lifesaving drugs to thousands of people. DOTS has a good track record for tuberculosis control in poor areas of the world, and if the same model for the delivery of antiretroviral drugs can be made to work at a national level, many lives can be saved and the risk of drug resistance kept low.
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A box of the five components of the DOTS strategy and a patient record chart for monitoring antiretroviral therapy are on bmj.com
Contributors and sources: All the authors have worked with several other partners on producing the national antiretroviral treatment guidelines and the national antiretroviral expansion plan, which they are now implementing. This article is based on the authors' collective country based experience and is supplemented by published, peer reviewed research on tuberculosis and antiretroviral therapy. Simon Makombe is an antiretroviral therapy officer in Malawi who has contributed considerably to the implemenation of the expansion programme.
Funding: ADH is supported by Family Health International, and EJS is supported by Management Sciences for Health. The national expansion of HAART will be funded mainly through the Global Fund to fight AIDS, Tuberculosis and Malaria.
Competing interests: None declared.
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