When to Start Treatment
New findings presented at this year's Conference on Human Retroviruses and Opportunistic Infections were overshadowed by public discussion of a change in the U.S. Guidelines on the Use of Antiretroviral Therapies. The changes represented something of a correction, or some say, a repudiation of the "hit hard, hit early" approach promoted at the International AIDS Conference in Vancouver in 1996. Researchers whose views were considered "state of the art" in 1996 were now all but hiding from the press. As usual, the truth wasn't quite that simple nor are the changes as dramatic as some think. They do, however, offer an important clarification on the use of treatment.
The issue of when to start anti-HIV therapy has been debated since 1986. While there are good theoretical reasons to support early treatment of HIV, doing so means coping with a complex interplay of drugs, HIV evolutionary processes (resistance), short- and long-term side effects and issues of personal choice. If there is any clear message from the last fifteen years of research, it is that there is no single treatment strategy that is "best" for everyone, no matter how much people might wish to have one. The decision to start treatment is a personal choice that can be informed -- but not dictated -- by the available scientific and medical evidence.
Although there were various opinions on when to start therapy prior to the use of Highly Active AntiRetroviral Therapy (HAART) in 1996, the availability and success of protease inhibitors led to a wide swing in favor of early treatment. Talk of the potential of "eradicating" HIV led many physicians to believe that everyone should be placed on treatment without regard for clinical symptoms or how long a person was infected. A careful examination of what researchers were saying, however, showed that they were only raising the hope of eradication in people who started treatment literally within a few weeks or months of first being infected. Nonetheless, the media translated the call to "hit hard, hit early" into a mantra that was interpreted to mean "treat everyone."
During this period, the Federal government called together a panel of experts to draw up "official" recommendations for the use of anti-HIV therapy in adults. They recommended then that people with CD4+ cell counts below 500, and/or with a viral load of 5,000 to 10,000 copies, should be "offered" treatment, and that treatment should be strongly encouraged for people with CD4+ counts below 200. The Guidelines never said that people "should take treatment" -- only that it should be discussed and offered. For people with CD4+ cell counts above 500, the Guidelines concluded that treatment was a matter of personal choice and opinion since there were no data either supporting or firmly discouraging its use. Still, many physicians interpreted the Guidelines as recommending that everyone should be on treatment, regardless of lab values or stage of disease.
The Outcome -- Four Years Later
There are several possible long-term consequences of the "hit hard, hit early" era of therapy, many of which were not initially recognized.
With factors complicating the use of early therapy becoming more apparent over time, the U.S. Federal Guidelines Panel revisited their recommendations, as had their European counterparts and the International AIDS Society. Though there really aren't any new data regarding the potential benefits of early treatment, there are now a lot of data about the potential risks. After a year-long review, the new Federal Guidelines now recommend that physicians discuss and "offer treatment" to people with CD4+ cell counts below 350 or viral loads over 30,000 to 50,000 copies. Some newly available data continue to suggest that most people will fare well even if they wait until the CD4+ cell count falls to around 200, though this provides little safety margin to accommodate individual differences or the differences seen between men and women on some lab tests.
Therefore . . . ?
For HIV-positive people and their doctors who wish only to read the charts of the new Federal Guidelines but not the accompanying text, things sound very simple: just put everyone on treatment when their CD4+ cell counts fall below 350 or when their viral load exceeds 30,000 to 50,000. Following such a rule, however, might still result in a good deal of inappropriate use of drugs because the health of a person's immune system cannot be described solely by the CD4+ cell count or viral load, nor can their response to treatment be predicted.
Studies cannot predict how any individual will respond to treatment, or how they would fare without it. All a study can do is report the average response seen in the groups studied. Some of the people in those studies will indeed have the "average" response described by the study analysis, but many others will do much better or worse. While it is true, for example, that there is a serious risk of getting pneumocystis carinii pneumonia (PCP) when a person's CD4+ cell count falls below 200, some people get the infection with a CD4+ cell count of 300 or even 400, while others coast along with counts below 50 CD4+ cells without any infections. Monitoring not just lab values, but also overall measures of general health including weight, minor symptoms, and your overall sense of well-being can provide important clues as to your individual risk of disease progression and help you decide if intervening with therapies is right for you.
People with the same CD4+ cell counts and same viral load do not all have the same risk of disease progression. By itself, the CD4+ cell count doesn't tell us enough. It's a good starting point, nothing more, nothing less. It's perhaps most useful when looked at over time, in the context of general trends. Other factors that should be considered in making a decision to start treatment include:
HIV-positive people and their doctors must understand that the U.S. Federal Guidelines or the International AIDS Society Guidelines -- anyone's guidelines -- are not meant to be rigid formulas that dictate the practice of medicine. They are just a generalized starting point for making decisions about treatment. There is no one "right" time for starting treatment that will work for everyone, and no planned or possible study will ever result in a precise universal recommendation. Over time, studies may add to our knowledge about how the various factors affect the decision to start treatment. They will help clarify matters, but they too will never lead to a "cookbook" solution that fits everyone and every circumstance.
In deciding when to start, many factors should be considered, including a mix of all we have learned from studies, and all that is known about the individual and his or her life situation. Once this is understood, it is generally easier to find the "right" time for an individual to start therapy.
While there may be no one "right" time to start anti-HIV therapy, there is certainly a "right" time to start managing HIV disease. Learning about and lining up benefits and support systems; improving diet, exercise and general health habits; choosing and developing a relationship with a doctor; setting up routines of regular health check ups, including Pap smears for women, (quarterly and twice yearly, respectively); learning about HIV disease and treatment options; and cultivating a philosophy of well-being are ways to intervene in HIV disease and take charge of one's health that can start today. There is no question that starting these activities earlier rather than later is beneficial. Project Inform has resources to help people consider these approaches to health and well-being.
This article was provided by Project Inform. It is a part of the publication Project Inform Perspective. Visit Project Inform's website to find out more about their activities, publications and services.