Death (HIV/AIDS A CHRONIC, NOT ALWAYS SO MANAGEABLE, CONDITION, 2010) ( HIV AND ACCELERATED AGING, 2010)
I think the p.c. word is morbidity . I recently had an argument with one of the very few friends iv disclosed to who stated , "people don't die from aids anymore". For whatever reason after 4 years despite three meds ( kaletra, truvada, instentra) I cannot achieve undetectable status. My doctor made a startling statement that he has had paitents 'survive' 5 or 10 years in virologic failure. What do you say to people who say Aids isn't fatal anymore?
Morbidity means illness. Mortality refers to pushing up daisies.
Your friend is woefully misinformed. HIV/AIDS is a slowly progressive disease that does not have a cure. That makes it a terminal (fatal) condition. Yes, we have made remarkable strides in treating HIV/AIDS and we are seeing dramatic decreases in both morbidity and early mortality. However, as your case dramatically illustrates, not everyone responds to the currently available antiretrovirals. Some folks develop resistance to the medications; others can't tolerate them due to side effects or toxicities. HIVers, even those who have responded well to treatment and have undetectable viral loads, are still more susceptible to heart attacks, strokes, malignancies and other conditions associated with chronic inflammation and advanced aging. For some HIV may be a "chronic manageable disease"; however, for many others it's anything but. Print out a copy of my blogs addressing these topics (see below) and show them to your clueless friend.
A Chronic, Not Always So Manageable, Condition By Bob Frascino, M.D. February 16, 2010
I'm undoubtedly the most optimistic guy in the galaxy, bar none! Really, I am. For instance, you know how some people are cup-half-full folks and others are cup-half-empty folks? Well, I'm a cup-runneth-over kind of fellow. Yet despite my unabashed and unbridled optimism about essentially everything in existence, I'm beginning to think the term "chronic, manageable condition," when applied to HIV/AIDS, may be overly optimistic or at least misleading, particularly for many of us who are positively charged and struggling to coexist with a virus that wants nothing more than to plant us six feet under!
While I freely admit that many of us who are virally enhanced no longer feel we have one foot in the grave and the other on a banana peel, I wonder: Do we really have a "chronic, manageable condition?" (I'm still new to this whole blogosphere thingy and commencing today's entry with a provocative prologue followed by an open-ended question suddenly makes me feel like Carrie Bradshaw at the start of a Sex and the City episode, typing away on her Mac in an uber-chic strapless fashion-forward empire-bodice camisole leotard and Prada cha-cha heels. But I digress. And besides, I'm dressed in trendy Rock and Republic jeans, Pumas, tank top and hoodie, just in case you were wondering. And before any of you ask, 2xist boxer-brief tighty-whities.) Now where was I? Oh yeah, chronic manageable conditions.
Personally, I tend to think of halitosis, hemorrhoids or even "the heartbreak of psoriasis" as examples of chronic manageable conditions. But HIV/AIDS? I'm not so sure.
One recent day, a number of real-life HIV/AIDS stories crossed my desk and they have fortified my position vis-?-vis HIV/AIDS as a chronic, but not always so manageable, condition. Let me, first, set the stage for this discussion and then give you a firsthand view from several HIVers who contacted me that day.
I received a very kind e-mail from a journalist who wrote a feature article about me several years ago for a local newspaper. She wrote to graciously volunteer some of her time to help The Robert James Frascino AIDS Foundation. (Megan, if you're reading this blog, it's great to hear from you again and I'll give you a call within the next few days!) In preparation for her March 2007 article, I recall we spent considerable time discussing how HIV/AIDS had become a much more treatable ("manageable") illness with the discovery and availability of potent combination antiretroviral therapy in the mid-1990s.
By way of comparison, I remember referencing a cover story written about me for the magazine section of the San Jose Mercury News in 1996, which carried the headline "Robert Frascino, M.D.: Casualty of War." It was a terrific article, but I would have preferred something along the lines of "Wounded in Action" for the title. Nonetheless, in 1996, just prior to the release of the first protease inhibitors, when the San Jose Mercury News article appeared, HIV was indeed a death sentence with a short shelf-life. I, like everyone else at the time, anticipated the virus would snuff out my life on this planet within a few short years. My, how things had changed within the few years that passed between these two feature articles.
There could be no doubt the new drugs had been nothing short of miraculous. After all, I was still alive, right? And not only had I survived, but I had thrived! So the focus of the more recent article reflected the reality of having, for the first time since the onset of the pandemic, effective treatment to combat the virus.
Much has been written over the past several years exclaiming the virtues of these life-sustaining wonder drugs while simultaneously proclaiming that HIV/AIDS has now become a chronic, manageable condition, like hypertension or diabetes. Antiretroviral drug advertising campaigns fueled this notion with glossy photos suggesting that taking pills would transform a frail HIVer into a sturdy, studly mountain-climber or sexy javelin-thrower. Is it any wonder that John Q. Public absolutely believes HIV/AIDS is a chronic, manageable condition? But is it really???
Also that day I received an e-mail from an "out HIV+ gay M.D." in a rural part of the country. He wrote:
"I have a male (straight) patient I have been seeing for 15+ years. Over the years he has had aseptic necrosis of both hips, both shoulders, and now the knees. (now opioid dependent from pain control) But most importantly at the moment, his 35" abdomen of 15 years ago is now 52" at the widest part (several inches about the navel) and he is losing balance because of this odd collection of weight, not to mention GI upset, short of breath etc. Do surgeons ever 'de bulk' all this visceral fat? It needs it because this is much more than 'cosmetic' and is severely compromising his quality of life. Thanks for any thoughts or advice."
Is HIV really a chronic, manageable condition for his patient? The answer to his query is not all that encouraging. HIV-associated central fat accumulation, visceral abdominal fat (VAT), is not amenable to surgical intervention. And there are no FDA-approved drug therapies for this condition. Lifestyle modifications (diet and exercise), as well as switching antiretroviral therapy, have had very limited success in reducing VAT. One drug, metformin, did show some benefit at reducing VAT, but accelerated peripheral fat loss (lipoatrophy). Neither testosterone nor thiazolidinediones has led to significant improvement. Recombinant human growth hormone (rHGH) has demonstrated some improvement in two large clinical trials. However, this treatment is costly and can be associated with significant side effects. The improvement seen was also temporary. There are some promising data using growth hormone releasing hormone (GHRH). My advice was to try to enroll his patient in a clinical trial of GHRH if he qualified.
That same day I received a question in my inbox in The Body's "Ask the Experts" forum from a woman who calls herself "Mommy of Three." This unfortunate woman is struggling and her chronic condition is far from being managed. I encourage you to read her post in full detail. She deals daily with health issues as well as life circumstances and past traumas that make effective HIV care virtually impossible for her. (If someone has ideas to help her, please feel free to comment!)
Later that day, another physician contacted me. He'd recently seroconverted to HIV positive. He wrote: "I find it very difficult to trust who to talk about this with. In fact I think this is the first time that I even put it in writing." He wanted to get in contact with me, for "some guidance from a physician-to-physician point of view," but he wanted us to only talk on the phone because of his "concern about the confidentiality of email communication."
I can think of no other chronic medical condition that would instill such fear. And what about HIV/AIDS's other "unique" facets, such as stigmatization, difficulties finding competent, compassionate health care, problems with employment, alienation from friends and family, disclosure issues and even criminalization? (Note to self: These are all nifty, bloggable topics. Note on note to self: Check to see if "bloggable" is a word.)
At the end of the day I received a question from an HIVer who complained his HIV medications were giving him intractable diarrhea and explosive gas. Further details revealed this was not your run-of-the-mill "Hershey squirts" and "trouser coughs." Rather, his pop-a-vein-in-your-forehead poopies would make Montezuma's Revenge seem like a case of constipation. And his "gas" was setting off sonic blasts so loud, I'm convinced he'll be getting fan mail from the seismographic people here in California for the next month.
Chronic, manageable conditions? Maybe not-so-much for these folks. And they are only the ones who contacted me that particular day! I have much more to say about this topic and how the "chronic manageable condition mantra" may actually be hindering our HIV prevention efforts. I invite you to stay tuned for "A Chronic, Not Always So Manageable, Condition, Part II."
As for what's left on my to-do list for tonight, I need to respond to the folks mentioned above: the chronic-not-so-manageables.
Robert J. Frascino, M.D.
HIV Causes Accelerated Aging: Has AIDS Become Acquired Inflammation Disease Syndrome? By Bob Frascino, M.D.May 3, 2010
I don't plan to grow old gracefully. I plan to have facelifts until my ears meet. -- Rita Rudner
Inflammation is the hottest topic in HIV/AIDS research. We've known for many years that, left untreated, HIV disease produces widespread inflammation. The higher the HIV plasma viral load the more dramatic the inflammatory response. Treatment with potent combination antiretroviral therapy decreases not only HIV replication and consequently HIV viral load, but also HIV-associated inflammation. More recently we've learned that even when we drive the HIV viral load to undetectable levels, we don't completely turn off the inflammatory process.
"So what?" you may wonder. Well, glad you asked.
This ongoing HIV-related inflammation is now being linked to or at least associated with a wide array of HIV comorbidities. (That's doctor-speak for nasty HIV compilations.) These complications are far from trivial. Ongoing HIV-related inflammation is being blamed for the lack of response to vaccinations, the increased incidence of non-AIDS-defining cancers, increased neurocognitive decline, the lack of immune reconstitution (CD4 counts that don't rise as expected with treatment), accelerated bone demineralization, accelerated hardening of the arteries leading to increased incidence of stroke and heart attacks, and the rise of the Tea Party Movement!
OK, I made that last one up, but the others are true. And here's the real kicker: HIV (presumably HIV-related inflammation) causes accelerated aging! Yep! We're talking "HIV Inflammaging!" Now I know what you're all thinking: "Damn! Now that's just not fair! Haven't we got enough to deal with?" And I agree with you! I will add this whole HIV inflammaging concept is still incompletely understood but it is rapidly evolving. In fact the evidence supporting this scary concept is piling up faster than AARP notices in my mailbox. Consequently I felt we should discuss it. Besides, the prescribed mechanism underlying all this malicious geriatric-inducing mayhem is immunological. Since that's my specialité, so to speak, I thought I should try to review what we know so far. (Before the Alzheimer's kicks in.)
There is increasing indirect, as well as direct, evidence that we HIVers are at increased risk of morbidity (illness) and mortality (pushing up daisies) from a wide variety of non-opportunistic, non-AIDS-defining, serious conditions like the ones I listed above. And it has become increasingly clear that inflammation underlies this entire worrisome problem.
One piece of supporting evidence comes from the SMART trial (Strategies for Management of AntiRetroviral Therapy). Clever title, eh? In this well-designed clinical trial, a treatment interruption strategy (intermittent use of antiretrovirals to maintain CD4 count above 250) was compared to ongoing uninterrupted treatment with antiretrovirals. The question that trial was designed to answer was whether reducing overall antiretroviral drug exposure would reduce non-AIDS-related complications. We knew some antiretroviral drugs were most likely increasing the risk of heart disease, stroke and liver failure in some patients. So we hoped that decreasing overall drug exposure would decrease these related problems.
WRONGO! The study was stopped prematurely (studius interruptus!?!?), because it was noted that HIVers in the drug-conservation group actually had a higher risk of these oh-so-annoying conditions (including death!) than those in the continuous treatment group! WOWZA, that was a shocker! The take home message was that the increased risk of these conditions was more closely linked to uncontrolled HIV replication than to drug toxicity. We sure didn't see that one coming!
A detailed analysis of all the biomarkers in this study showed markers of inflammation (C-reactive protein, interleukin-6) and a blood coagulation marker (D-dimer) were significantly higher in the patients who were in the intermittent antiretroviral arm of the study. Stay with me; I know this is a bit complicated! (We immunologists just love the uber-complexities of life and death. Yeah, I know we're weird, but hey, we wind up figuring out really cool and scary stuff like the mechanisms responsible for HIV's grow-old-quick trick!) So what we learned from the SMART trial is that ongoing HIV-induced inflammation and a procoagulant state (increased risk of forming blood clots) underlie the increased risk of non-AIDS-related events observed in us HIVers and that in turn accounts for our increased mortality!
So AIDS: Acquired Immunodeficiency Syndrome may wind up being AIDS: Acquired Inflammatory Disease Syndrome!!!
The San Francisco Department of Health has recently become the first to recommend that all HIV-infected people be treated immediately with combination antiretroviral drug therapy without regard to CD4 count or HIV plasma viral load. This is a dramatic policy shift from previous recommendations and published guidelines that advised delaying antiretroviral therapy until CD4 counts had fallen into a certain range. The impetus for the policy shift is the concept of "inflammaging" supported by clinical trials, such as the SMART trial discussed above.
The concept that antiretroviral medications are toxic and consequently that we should wait for as long as possible to begin treatment has been replaced with a new paradigm: Although antiretroviral drugs are far from benign, they are less toxic than uncontrolled viral replication and its resultant inflammation.
Widespread early treatment may not only be the best treatment option for the virally enhanced individual, but also have a secondary beneficial effect from a public health HIV-prevention perspective. We know that when antiretroviral therapy drives HIV plasma viral load to undetectable levels, the risk of HIV transmission decreases significantly. Consequently, if a greater portion of positively charged folks is on effective treatment, in essence the "community viral load" decreases and the community risk of HIV transmission falls.
The story of "accelerated immune aging" or what we immunologists refer to as "early senescence" in HIV disease is becoming an increasingly complex and, at least for us whacked immunologists, fascinating aspect of HIV/AIDS. It involves dysfunctional thymus glands, microbial translocation, interferon-inducible genes and proteins, immune activation and shortened telomeres. Yeah, I know, most of you find this stuff about as fascinating as reading a book on elocution authored by George "Dubya" Bush. So I won't go into great detail (unless an overwhelming number of you write in requesting the nitty gritty immunologic details, in which case I'll be happy to pontificate). For now let's just say a lot of complex science and immunologic research is all pointing in the same direction: HIV is accelerating our aging process. (Suddenly I have the Beatles classic "When I'm Sixty-Four" running in a feedback loop through my brain: "Will you still need me, will you still feed me, when I'm sixty-four?")
Speaking of aging, as you may recall from my first HIV and aging blog entitled "Time Warp," I discussed "Angelennie," my loveably dear octogenarian parents. I need to provide you with an update. Just as they were settling into their "new normal" life at the snazzy and stunningly lovely assisted living facility at Saratoga Retirement Community, my mother suffered a massive stroke. She occluded her left middle cerebral artery, which resulted in paralysis of the entire right side of her body and face and inability to speak. This type of severe stroke has a 50% mortality rate, and the other 50% generally are left paralyzed and unable to speak. This horrendous event is a consequence of aging.
Despite the grim prognosis, however, miracles do happen. Due to the fact the stroke was witnessed by my dad, who immediately notified the facility's phenomenally attentive emergency response team, my mother was transported within minutes to a nearby stroke center. Very aggressive treatment with the clot-busting drug (TPA) given both intravenously and intra-arterially failed to dislodge the clot. However, fortunately the stroke center was equipped to perform a very risky procedure whereby the clot was dislodged mechanically with a MERCI retractor. (MERCI = Mechanical Embolism Removal in Cerebral Ischemia.)
She survived, and after several touch-and-go days in the intensive care unit she began to move her right side and say a few words. Within a week of the stroke, instead of being dead or paralyzed, she was being discharged from the hospital and had become something of a celebrity in the local medical community.
The reason I'm sharing this remarkable story is to emphasize three points:
Aging can and does cause catastrophic events. Modern medicine can work miracles, which were unimaginable just a few short years ago. There is always hope, and good karma rocks! I'll have more to say about Acquired Inflammation Disease Syndrome sometime soon. But now, it's time for me to visit my Lazarus-Mom!