This issue of ACRIA Update focuses on the immune system and immune-based therapies. AIDS research has provided us with better understandings of both HIV itself and the immune system. Previous issues of our newsletter have often focused on the virus - discussions of antivirals, side effects and drug resistance. But for HIV treatment to advance further, the immune system side of the equation requires equal attention. This issue offers overviews of how the immune system works and the concept of immune restoration. We've also asked some of our colleagues to look at specific therapies and strategies that might give the immune system the kick in the butt it needs to help slow down HIV disease progression and improve immune function. HAART has dramatically improved the lives of many PLWAs, but the limitations of antiviral therapy highlight the need to engage the immune system in the fight against HIV.
On January 1, 2002, the Community Research Initiative on AIDS (CRIA) officially became the AIDS Community Research Initiative of America (ACRIA). We made this move to reflect the agency's current activities as a national HIV/AIDS clinical research and treatment education organization.
The discovery of HIV in the mid-eighties led to an intensive search for therapies that might inhibit the virus's life cycle, a search that eventually produced the sixteen antiretroviral drugs that are on the market today.
Interleukin-2 (IL-2) is the immune-based therapy that has been most extensively studied in HIV. Many people continue to be intrigued by its potential, yet questions about IL-2 remain unanswered, including the most basic one - is it an effective HIV therapy?
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 page 10), and still others hope to create LTNPs by using therapeutic vaccines.
As the smoke of hope dissipates for eradication of HIV from the human body and the limitations of antiretroviral medications become all too apparent, efforts are being renewed to examine a role for immune-based interventions to help control HIV infection and potentially reduce ongoing exposure to antiretroviral medications.
After becoming HIV-positive, most people usually remain physically well for years. During this time, despite outward appearances, HIV is constantly attacking the immune system. As the damage from HIV builds up, levels of important immune cells called CD4 cells gradually decline. Eventually the body is unable to repair the damaged immune system, leading to an AIDS diagnosis.
The human immune system is a dazzlingly complicated mix of many different cells, tissues and chemical factors that work together to try to maintain health. The immune system has evolved over billions of years to accomplish a multitude of tasks, including responding to infections but also tolerating substances - like pollen and food ingredients - that pose no danger to the body.
The ability of Highly Active AntiRetroviral Therapy (HAART) to suppress HIV replication, increase CD4 cell counts in the blood, and prevent or delay opportunistic infections is now well documented.
It seems like only yesterday that newsletters and web sites were filled to the brim with research reports about structured treatment interruptions (STIs). These reports on "drug holidays," once full of hope and zeal, now appear scattered and rather lackluster - a possible indication that STIs are a trend of the past, a high-minded theory that failed to pan out in clinical trials.
Just when everyone starts getting used to viral load tests, with all their confusing "logs" and "copies" and "undetectable levels," another family of lab tests with its own bewildering lingo arrives on the scene.
Resistance testing is fast becoming part of standard of care for treating people living with HIV. It is yet another tool, along with viral load and CD4+ cell counts, to optimize the selection of anti-HIV therapies.
The introduction of resistance testing technology into the clinical practice of HIV medicine has offered me and my providers at the North Bronx Health Care Network of Jacobi and North Central Bronx Hospitals an opportunity to revolutionize our approach to HIV treatment.
Like stepping onto the bathroom scale the day after Thanksgiving, viral load assays and drug-resistance tests have an annoying habit of telling the truth when we least want to hear it.
The Winter 2000/2001 issue of CRIA Update included several articles that explored the topic of quality of life. In preparing that issue, we saw an opportunity to share with CRIA readers the inner workings of this important area of clinical research. What better way to illustrate the advantages and limitations of different approaches to quality of life measurement than to conduct a survey of our readership?
CRIA is pleased to introduce Eugen Vartolomie, MD as our newest researcher. Dr. Vartolomie comes to us from Bronx-Lebanon Hospital Center where he conducted HIV and AIDS related research within its Infectious Diseases Clinic.
CRIA is a co-sponsor of NATAF 2001 (North American AIDS Treatment Action Forum), which takes place December 2-5 in Vancouver. This conference, sponsored by the National Minority AIDS Council (NMAC), provides treatment advocates, activists, educators and people living with HIV the opportunity to broaden their knowledge of HIV treatment issues, build advocacy skills, and develop strategies to advocate for people living with HIV/AIDS within their communities, nationally and internationally. A limited number of scholarships to NATAF 2001 are available.
CRIA has begun enrollment on this multicenter study that follows-up on a national level a previous pilot study that CRIA sponsored and conducted. This current 26-week, double-blind, randomized, placebo-controlled study looks at the effectiveness and safety of Serostim® (human growth hormone) when used to treat the abnormal fat distribution that occurs in patients treated with antiviral drugs for HIV infection.
I use this phrase almost daily as I discuss treatment strategies with people considering their options. We have to understand that there is not one medication or one combination which will work for everyone. Many factors go into determining a first, second, or subsequent regimen. Side effects, food restrictions, and convenience factors all add to the complexity of the decision. And that is just the beginning of the growing complexities of treatment.
The historical record of progress in AIDS research lies not only in the medical literature, but also in the community-produced clinical trial directories that have tracked experimental protocols as they opened and closed over the years. Studies of failed treatments generally don't get published, and many of yesterday's therapeutic hopefuls have faded from the collective memory.
The Summer 2001 issue of ACRIA Update takes a look at the direction of AIDS research - where we've been, where we are and where we're going. We've invited a diverse group of researchers, clinicians and community members from varying disciplines, experience and backgrounds to offer their perspectives on the current state of AIDS research.
People with HIV have a bit more clarity about when to start anti-HIV treatment, thanks to the recently revised federal treatment guidelines. But the question regarding which regimen to start with remains unanswered. One type of regimen in particular-a combination of three nucleoside analogues without either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI)-is one of today's options.
Scanning the list of all the drugs currently in development, it's hard not to notice some very familiar names: AZT (Retrovir)® d4T (Zerit)® efavirenz (Sustiva)® nelfinavir (Viracept). While these four drugs are approved and being used by a large number of people, their manufacturers have taken them back to the lab for pharmaceutical facelifts.
Kaletra (lopinavir), Abbott Laboratories' recently approved protease inhibitor (PI), has caused a great deal of confusion among researchers and healthcare providers. The reason for this is that nobody fully understands this drug's resistance profile. In one study presented at the 8th CROI, a team of researchers from Abbott examined 96 HIV samples collected from people on treatment for the first time who saw a rebound in their viral load while taking either Viracept (nelfinavir) or Kaletra with Zerit (d4T) and Epivir (3TC).
Enormous strides in HIV treatment have been made over the last several years. Fifteen approved anti-HIV drugs have saved thousands of lives and have helped many people return to mostly healthy, productive lives. Unfortunately, these drugs are not perfect. This is especially true for people who have used these drugs in the past and no longer respond to them.
It's hard to believe, but it has been more than five years since the protease inhibitors (PIs) made their therapeutic debut and forever changed our approach to managing HIV. Perhaps the most impressive aspect of this milestone is that researchers and healthcare providers are continuously finding new and improved ways to use this powerful class of anti-HIV drugs. For evidence of this, one doesn't need to look much further than the current trend of dual-protease inhibitor therapy-the combination of two PIs with two nucleoside analogues.
Triple combination therapy has been around for over five years now - we should all be getting the hang of it, right? Well, we certainly know a lot about treating HIV disease. But with more medications to choose from, more knowledge of the long-term side effects of therapy, and more sophisticated laboratory tests such as drug resistance profiling, things are getting trickier.
"Have you ever heard of AIDS?" Since it was March of 1982, I hadn't. But I was glad to have someone put a name to my chronic illness. I asked the intern in the emergency room what treatment he suggested, and he replied there was none. "Okay," I said "I'll find something on my own."
The question of when it's best to begin antiretroviral therapy may be as controversial and frustrating as any of the many HIV treatment questions to which we have no clear answers. The US Department of Health and Human Services (DHHS) HIV treatment guidelines were revised in February, and the biggest change in the guidelines addresses this question.
Thanks to ongoing research and people's real life experiences, our understanding of HIV and its treatment continually expands. More treatment options are now available to people living with HIV than ever before. Having more options can be overwhelming and confusing. So many drugs with so many names. So many things to keep track of - viral load, CD4 count, and results of resistance tests.
This information is designed to support, not replace, the relationship that exists between you and your doctor.