Wondering Aloud: Theories of One (Quasi) Long-Term Non-Progressor
Speculation abounds as to what makes a long-term non-progressor (LTNP), as do definitions of exactly what a LTNP is. Some have looked at the maintenance of HIV-specific CD4 cells, others at cytokines like IL-10 (see "The Role of IL-10 in Long-Term Non-Progressors"), and still others hope to create LTNPs by using therapeutic vaccines (see "Therapeutic Immunization"). In my own case, I've wondered for years if I may have stumbled on a way to slow disease progression by the use of a simple, cheap and non-intuitive treatment.
I trace my infection back to 1981 or earlier, based on frozen blood from 1984 and a CD4 count below 500 in March of 1982. Though I'm still healthy twenty years later and have never taken antiretrovirals, I don't really fit into the category of LTNPs, who have normal CD4 counts around 1,000. My CD4 count has hovered around 300 for years, and my only clear-cut symptom of HIV disease has been occasional thrush (though I do struggle to maintain my pre-HIV bodyweight).
My personal theory has to do with a fortunate hospitalization in 1985. After months of flu-like symptoms and a drop in weight of thirty pounds, I was hospitalized due to extremely high calcium levels. I was finally diagnosed with sarcoidosis, an autoimmune disorder not associated with AIDS in which the immune system attacks one's own tissues. Prednisone, a corticol steroid, cleared up my symptoms immediately. A year later I stopped the prednisone, but I eventually went back on it when my symptoms returned. The trick was moving to alternate-day dosing, which eliminated all side effects but still controlled the sarcoid.
I thought my body was controlling HIV on its own, but I was surprised to learn years later that there was some evidence the prednisone might actually be the cause of my good health. HIV chronically stimulates the immune system, causing the over-production of a number of immune system components such as immunoglobulins, tumor necrosis factor and alpha-interferon. It also increases activation of T-cells, which leads to greater HIV replication. Using immunesuppressants to dampen some of this over-stimulation has been proposed, and some small studies have shown benefits for prednisone in people with HIV, but the data is far too sketchy to suggest using this approach in clinical practice.
The National Institutes of Health (NIH) began a study in 1999 to specifically look at the benefits of prednisone in people with HIV. Unfortunately, they took the "more is better" approach, using 40 mg a day -- far too high to take on a long-term basis (I'm currently on 15 mg every other day). When pre-clinical indications of bone loss were found, the study was stopped. Since the NIH rarely re-visits failed hypotheses, we'll most likely never find the answer as to whether a drug like prednisone could be beneficial if started early in disease.
Now, my lack of progression could be due to the sarcoid itself -- the theory being that the sarcoidosis is creating excess CD4 cells and HIV is killing them off, leading to a steady state. But since my sarcoid is so well-controlled by the prednisone, I don't think that's the case. One could also say that I'm just a very slow progressor, but whenever I stop the prednisone I feel far less healthy, and HIV-related symptoms like sinusitis and rash start appearing.
It bothers me that I may have chanced on an effective way to slow HIV disease, but that no one else will benefit. If low-dose prednisone actually works to slow progression, it would be the answer for people who don't have advanced HIV disease, particularly for those in developing nations who can't afford combination therapy which costs over $10,000 a year. Prednisone is one of the cheapest drugs in the world, and a regimen of one pill every other day is feasible in even the most resource-poor settings.
Of course, the very fact that prednisone is cheap and offpatent makes it extremely difficult to find funding for the controlled studies needed to prove its benefit. And the necessary trial would be considered unethical by many, since it would need to randomize people to either prednisone or placebo, with no other antiretrovirals to mask disease progression. But with the new U.S. recommendations that treatment can be delayed until CD4 counts drop below 350, and with the British recommending people wait until 200, a trial could be designed for those with higher CD4 counts.
So here I sit, wondering if it is the prednisone that's keeping me healthy, wondering if there will ever be a way to prove it, wondering what would have happened to me if I hadn't started the drug sixteen years ago, and wondering if we aren't missing entirely different ways to control HIV disease, since almost all research focuses on antiretrovirals and not on treatments that support the immune system.
Mark Milano is a treatment educator at ACRIA and a longtime AIDS activist.
This article was provided by AIDS Community Research Initiative of America. It is a part of the publication ACRIA Update. Visit ACRIA's website to find out more about their activities, publications and services.