In the wake of the XIII International AIDS Conference, the concept of "best practices" in HIV management has become a touchstone. The "best practices" concept implies drawing on local capacity and experience to create a practical high-quality standard of care. For HIV, the most widely suggested strategies for resource-poor regions include STD management and treatment of opportunistic infections-but no antiretrovirals. To some stakeholders, including the pharmaceutical industry, an embrace of the "best practices" concept offers the hope of ending the all-or-nothing debate over antiretrovirals in the developing world. But while some doctors (see accompanying article on Rakai) embrace this approach, others, like Peter Mugyenyi, head of the Joint Clinical Research Center (JCRC) in Uganda, fear that the new catch-phrase will allow some people to dodge responsibility for meaningful improvements, including the drug combinations that constitute HAART (highly active antiretroviral therapy (HAART).

"'Best practices' is emerging as international jargon," says Mugyenyi, "People don't really know what it means."

In more than a decade of AIDS work in Uganda, Mugyenyi has rarely taken his eyes off the prize, in this case, an uncompromising standard of care for his patients. In 1992 he spearheaded the first vaccine trial on the African continent. JCRC treats the majority of the small population of Ugandans currently on antiretrovirals. It in addition sees patients from neighboring countries, like Tanzania, Kenya and Rwanda, who are wealthy enough to fly to Uganda for monitoring and medication. The barrier to treating more patients is financial, not technological. Even with its international clientele and a transport system for "up-country" samples, Mugyenyi laments that JCRC is using only a twentieth of its capacity for viral load and CD4 cell monitoring. Rather than assuming that antiretrovirals cannot be used in Africa, he argues that treatment should rise to the level made possible by his and other centers of excellence scattered around the continent. As these centers reach their capacity, further infrastructure could be developed to accommodate increasing drug use. amfAR sat down with Mugyenyi at the JCRC to hear his views.

How do you define best practices?

My definition of good practices is that it is the most effective method and means of doing something in a specified location. The crucial aspects of good practices are:

• Is it the most effective?
• Is it proven?
• Where is the relevance of local factors in areas where it is being applied?

When you say the most effective method available, what are the parameters you are thinking about using, particularly in the context of HIV?

The most important thing in a developing country is the reduction of new cases. Voluntary counseling and testing is the single most important practice on which many other issues hinge in HIV. Expansion of testing is essential-you cannot tackle the problem unless you know its magnitude. In Uganda, we are now going into the second generation of strategies for HIV reduction. We had the first generation, which was aimed at bringing about behavioral change through information to the public. The second generation means availing ourselves of scientific tools [for diagnosing and tracking the disease]. We need to evaluate and implement new practices that strengthen HIV risk reduction strategies.

Mother-to-child-transmission programs have provided a compelling argument that willingness to learn one's status is linked to availability of some kind of medical management, either for oneself or, in the case of pregnant women, for their infants. In order to ask people to be tested, then, there has to be some kind of functioning standard of care.

That is an important point. Take the situations in Uganda and Kenya. In Kenya, we have places where the new cases of HIV are increasing annually. In Uganda, new cases are decreasing annually. But it is crucial to know that it has reached a stage where it is beginning to plateau. And it is plateauing at unacceptably high rates of HIV incidence-approximately 10 percent of the population. It is from this already-infected group of people that the infections are coming to the community, so unless measures are implemented to provide hope and care and treatment to them, all the progress that has been made in stemming the epidemic will not advance much further.

What are the important pieces of a treatment-oriented standard of care?

The program should be in three categories:

• The first is support and counseling.
  
  
• Secondly, they need treatment for opportunistic infections. This can easily be introduced into existing programs [like those set up for tuberculosis treatment],
  
  
• and then, of course, we need increased accessibility of antiretrovirals.
  

Common sense dictates that in the near future-and it might be nearer than we think-that antiretrovirals will come to be [widely available] in developing countries. Already, there is a huge pool of infected people which is continuing to broaden. Inevitably, antiretrovirals will come to be used more widely in these areas. Therefore, we need to make worldwide preparations and invest funds to address this inevitable method of managing the epidemic. Furthermore, we should abandon the fatalistic view that antiretrovirals cannot be used in developing countries.

For most HIV-infected people in Africa today, though, accessing antiretrovirals still feels like a remote goal. A lot of them are eager to know more about the second piece of what you are talking about-other forms of treatment they could be looking for and asking for that might be put into some kind of best practices guidelines.

Given the opportunity, many people are going to talk about treatment of opportunistic infections as the best practice for developing countries. They are only partially correct, and in most cases, they are using that method to mislead the populace of a developing country to believe that there is a strong option [for managing HIV] in treatment of opportunistic infections.

Let me explain. When they talk about treatment of opportunistic infections, it boils down to treatment using cotrimoxazole, or Bactrim. I want to state here that this is chosen not entirely because of its medical effect, but because it is an easy option. It is being flaunted by international organizations to save face because this is a drug which is available [through generic production], and it makes them appear as if they are doing something about the epidemic, and not just abandoning it.

So we have yet to see a feasible, OI-oriented approach emerge from the international community?

They are avoiding the most life-threatening opportunistic infections. These are the "big five":

• tuberculosis,
• cryptococcal meningitis,
• toxoplasmosis,
• cytomegalovirus
• and cancers associated with HIV.

Nobody is including these in a program of treatment of opportunistic infections, with the possible exception of TB. So when we talk about other strategies [besides antiretrovirals], we need to put it in perspective. People are going for the soft option and are not entirely addressing the issue. Yes, there should be proper treatment of opportunistic infections, but this needs to be understood for what it is. The ultimate goal is to give patients the most effective drugs, which are antiretrovirals, and all efforts should be made to ensure that these drugs are made available at cheaper - much cheaper - prices.

It sounds like you feel that best practices can be used to justify a kind of medical relativism?

There's no question. I started by talking about the importance of appropriateness [to location and culture] in developing best practices. This also works, to some extent, to our detriment. We have demonstrated here at JCRC that the drugs can be administered the same way as they are in Western countries; we have further demonstrated that when we use antiretrovirals here, we achieve the same effects related to health and quality of life. The biggest lie-that's how I put it-being told is that antiretrovirals cannot be used in Africa at the moment.

Is there particular research that you would like to see done in African countries to substantiate "best practices," including the use of antiretrovirals?

Absolutely. Regarding antiretrovirals, we need to continue researching antiretrovirals which can be used to treat a population whose level of education may not be very high. We need to do research into how these drugs can be used to maximize their effectiveness in this environment. An example of this may be shorter-term antiretrovirals, like structured, supervised stopping of treatment. We can also look at combinations of antiretrovirals with therapeutic vaccines. People who are not going to get antiretrovirals are inevitably going to develop horrific complications and opportunistic infections. We also need to do research on the ways that we can deal with them.

In terms of managing HIV infection, how do you think goals related to monitoring and viral suppression could or should be shifted away from a Western standard of care?

The importance of viral load has been overstated. If somebody has advanced HIV disease and is showing signs of esophageal thrush and you give him antiretrovirals, that person will improve. If you do viral load on that patient, all you are going to have is a more academic and flamboyant way of treating him. Treatment is very effective, even if you haven't had a viral load, so there is a lot of intellectual dishonesty.

Do you think that the international research community has reached a point where it is ready to accept studies that generate "best practices" which depart from the Western standard of care, without raising an ethical hue-and-cry?

Nobody has ever wanted to do high-profile antiretroviral research in Africa. What researchers have been prepared to do up to now in developing countries is what I call lackluster research. And they have avoided, like the plague, any research that involves big investments in Africa, like antiretrovirals. As far as ethical determinations, those should be left up to the local researchers and government. We do not want ethical double standards, but the peculiarities which come about because of social, economic and geographical differences should not stop research in developing countries. Instead, these issues should be addressed by ethical committees that include local representation so that all parties can move forward.

Small studies of antiretroviral therapy in developing countries show that there is already resistance circulating among patients who are starting their first "official" course of therapy. Do you feel that we're in a window period before resistance becomes a much larger problem in African countries; and what steps would you like to see to counter this trend?

I see this as a warning to pharmaceutical companies and international aid organizations. In developing countries, black-market antiretrovirals are becoming the biggest source of antiretrovirals, and these drugs are going to be increasingly used by the community outside of medical institutions. In Kampala, the Joint Clinical Research Center is the biggest formal user of antiretrovirals-and sees not even a half of the users of antiretrovirals in Kampala. Therefore the best way forward is not to try to prevent people from using these drugs. The best way forward is to make the drugs affordable, widely available and demystified, so that they can be dispensed to patients under medical supervision.

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