Chapter 2
Delivering treatment: a practical new approach
Despite resource constraints and technical obstacles, health care planners and treatment providers are working in many settings to scale up treatment as rapidly as possible, expanding from small pilot projects to national programmes. To enable this to succeed, the 3 by 5 initiative incorporates a practical "engineering" or "system design" approach. The plan is to develop innovative system designs and treatment protocols that can be scaled up even when the usual medical resources are in very short supply. This depends on streamlining and simplification of programme logistics, delivery of treatment and monitoring. The simplified strategies should allow nurses or clinical officers to treat patients within a physician-supervised treatment team, with community health workers providing follow-up support and adherence monitoring. Pilot projects have shown that, with proper supervision and streamlined treatment models, community health workers can shoulder much of the daily burden of delivering and supporting treatment (see Chapter 3).
Reducing complexity is necessary in order to accelerate the roll-out of treatment in areas with weak health care systems and a severe shortage of trained health professionals. Simplification applies to drug regimens and biological monitoring procedures recommended in WHO guidelines. It also covers protocols for treatment delivery, patient monitoring and support, and drug procurement and supply management. Such simplification does not imply poorer outcomes for patients than would be the case in wealthier countries. Many aspects of delivery, programme logistics and monitoring can be streamlined while still providing patients with excellent care.
In its new streamlined treatment guidelines, WHO has cut the number of recommended first-line treatment regimens from 35 to four. All four regimens are widely used in high-income countries and are highly effective (11). They use two different classes of antiretrovirals, reserving the protease inhibitor class for second-line therapy, and can be given to children, an important advantage for family therapy.
These four regimens do not require a cold chain, are widely available and cost less than regimens based on protease inhibitors. They use few pills, and the four combinations cover a variety of circumstances including tuberculosis coinfection and potential pregnancy. Other important advantages concern laboratory requirements and toxicity profile. Fixed-dose combinations are single pills containing all three antiretroviral drugs belonging to a triple therapy. Availability in a fixed-dose combination is an important criterion for preferred simplified first-line regimens. Weighing all these factors, the use of nevirapine-based regimens, particularly the d4T/3TC/NVP combination, is most suitable for initial therapy in resource-poor settings.
In addition to their logistic advantages, simplified treatment regimens, fixed-dose combinations and reduced pill count are much preferred by patients. They help ensure that patients adhere to treatment and that regimens work longer. Thus they can be expected to reduce the risks of drug resistance (11).
Laboratory testing and diagnostic tools for monitoring the health of people living with HIV/AIDS must also be simplified and made more readily available to the poorest populations. Evidence shows that tests such as total lymphocyte count and haemoglobin colour-scale blood tests can be used where more sophisticated tests for viral load and CD4 cell count are not yet available. The simpler tests, combined with clinical evaluations by adequately trained health workers, can be effective in monitoring the progress of AIDS, the effectiveness of treatment and side-effects, even in settings with weak health infrastructure (11-14).
Building on the simplified drug regimens, WHO has developed streamlined protocols for treatment delivery which aim to facilitate treatment scale-up, above all in the many areas where physician shortages are a major constraining factor. With simplified treatment models, it should become possible to decentralize antiretroviral delivery progressively to the health centre level; this is vital to reach the people most in need. Treatment can be initiated in facilities at all levels of the formal health care system, wherever the following are in place: HIV counselling and testing; personnel who are trained and certified to prescribe treatment and follow up patients clinically; an uninterrupted antiretroviral supply; and a secure, confidential patient record system. Rolling out treatment under this model will pose many complex challenges. It will require high standards of operational research to help identify what works and what does not, and why, and to provide rapid feedback and dissemination of that knowledge.
Drug supply management is a significant challenge in many regions hit hard by HIV/AIDS, but focusing on a small number of simplified drug regimens and using fixed-dose combinations should make it easier. Drugs are also a major part of the overall cost of 3 by 5 (see below), and minimizing these expenses is important to programme sustainability. WHO will work with countries and implementers to obtain the lowest possible prices on antiretrovirals of assured quality.
Antiretroviral drug resistance: acting now to prevent a major problem
Although the benefits of antiretroviral drugs are universally recognized, there is concern that their widespread and inappropriate use could cause the virus to develop resistance to them, thus creating a major new public health problem. The question arises as to whether such resistance might be accelerated by treatment expansion.
Virus strains with reduced sensitivity to zidovudine, the first drug used to treat HIV infection, were first observed in 1989, three years after it was introduced. Subsequently, resistance to every currently licensed antiretroviral drug has been observed (15).
WHO regards a surveillance system that enables monitoring of HIV drug resistance as an essential component of treatment scale-up. In this work, WHO and its partners are seeking the full support of the global HIV/AIDS scienti?c and public health community. WHO has established a coalition of 50 of the world's experts in policy, clinical management, and the science of HIV drug resistance (HIVResNet) to develop guidelines on how to conduct resistance surveillance in different settings and population groups.
Gathering reliable global data on the level of HIV drug resistance and its transmission has so far been extremely difficult. The prevalence of resistance in countries where antiretrovirals have been available for some years ranges from 5% to 27%. Recent data from 17 European countries showed that 10% of untreated patients carry drug-resistant virus. Very little data are available from the developing countries that will implement antiretroviral programmes, and much more information is required (16).
The threat of increased levels of resistance cannot be an excuse for not delivering life-prolonging therapy: it has not been a reason to delay universal access in developed countries. Instead, monitoring HIV drug resistance and developing approaches to reduce its emergence and spread are required.
WHO and its partners have established the following objectives:
- to track HIV drug resistance and assess its geographical and temporal trend;
- to understand more completely the determinants of resistance, especially adherence to treatment and factors that undermine it;
- to identify ways to minimize its appearance, evolution and spread;
- to provide information to international and country-level policy-makers through a rapid and easily accessible dissemination system.
WHO has identified the need to give strong support to global surveillance of antiretroviral resistance. Since December 2003, WHO's Guidelines for HIV drug resistance surveillance have been available on the WHO web site (17). These cover important aspects of a high-quality surveillance system such as sampling, data collection, laboratory testing, data management and analysis, quality control and ethical issues. The development and implementation of the HIV-resistance surveillance system will be primarily supported in high-burden countries where antiretrovirals are currently not widely available. Gathering data on HIV drug resistance prevalence in those areas will allow a baseline picture that can be compared with data obtained over time.
WHO and its partners are developing and implementing systems to measure HIV drug resistance in treatment-naive people (those who have not taken antiretroviral medicines before) in 20 countries and to monitor HIV drug resistance among treated people in five countries. By 2005, 40 countries will have implemented surveillance systems and 15 countries will have monitoring systems.