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!
Want to get in touch with Dr. Bob? You can reach him through his "Ask the Experts" forum, by sending a message to the Robert James Frascino AIDS Foundation, or by leaving a comment for him below. (If it's a private message, or if it includes personal info such as your e-mail address or phone number, we won't post the comment, but we will send it along to him.)
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Comment by: leon
Thu., Mar. 24, 2011 at 4:12 am EDT
hey Dr. Bob, i would be very intersted in hearing more about the early senescence. as a recently diagnosed medical student and former scientist, i find the nitty gritty a great way for me to cope with my status.
also, your blogs are fantastic.
Comment by: Douglas A.
(San Francisco, CA)
Fri., Oct. 29, 2010 at 9:45 pm EDT
Dr. Bob-- Being in my early 60's and "new" to HIV life (diagnosed 2 yrs. ago, that's another story..), I greatly appreciate the kind and manner of information you've shared. Intuitively, I wanted to start medicine treatment asap and my wonderful team of HIV practitioners at the time went along with me. I'm delighted to hear it was a good choice. I also had a quadruple bypass two years ago (and the stars were in what?) leading to questions then and currently about inflammation. I suffer from noticeable but not debilitating memory issues and general fatigue issues. Thoughts about 1. reducing inflammation and 2 HIV medication side-effects..not the ones on the 5 or 6 pages with the packaging, but actual real life side effects that people talk about.
Comment by: Trevor
(San Diego, CA)
Sun., Jul. 11, 2010 at 2:11 am EDT
Dr Bob, what a downer article you wrote--all this time i am thinking i am doing well and the right thing by getting down to undetectable and looking and feeling good and you make light and jokes of our condition. What possible use is this information to us but to cause more anxiety and worry? Re-read the hippocratic oath and be Positive (in the strictest sense of the word).
Comment by: Brian V
(Tampa Bay. FL )
Tue., Jun. 22, 2010 at 6:00 am EDT
I have had lifelong allergies and asthma and have been HIV+ since 1997. I beleive that I have been suffering from the inflammatory effects that you talk about. Is there any evidence that a person with allergies and asthma may be more prone to experiencing these inflammatory problems? And what tests or treatment is there for people who have these problems?
Comment by: jo ann
(ann arbor, mi)
Sun., Jun. 20, 2010 at 4:20 pm EDT
Count me as a vote for more "geeky" immunology info, which in your hands is not at all like a book by "W" on elocution but quite interesting and even fun.
Comment by: hot dude
(central south jusey)
Fri., May. 28, 2010 at 9:43 pm EDT
dude dr you rock theres always problemos but theres always hope never lose hope never give up thanks dr B!!!
Comment by: Dan
( Melbourne, AU)
Fri., May. 28, 2010 at 9:19 am EDT
Lucky I was a Goth as a teen and hence had my mid-life crisis at age 17. Makes getting older faster not quite so hard to deal with LOL. Anyway, thanks to Einstein time is all relative. As long as I'm still healthy & functioning with HIV I'm happy. Deal with that mountain when I come to it.
Comment by: John
Sat., May. 22, 2010 at 6:39 pm EDT
Here all the time I thought I was getting old cause I turned fifty!!! All I can say, "It's better than the alternative.. :)
Comment by: Rece
Tue., May. 18, 2010 at 8:45 pm EDT
I love your blog and advice for you give people. It is stright foward and so so so flipin funny (top fun, ding-dong, taly-wacker). Please keep up the great work !
Comment by: teresa
Mon., May. 17, 2010 at 1:43 pm EDT
Thanks Dr. Bob. Your wit is never wasted and your insight is always appreciated. Many blessing to you and your mom.
Comment by: Scott Berliner
(New York, N.Y.)
Thu., May. 13, 2010 at 3:03 pm EDT
I am a pharmacist that has specialized in HIV since the 80's. I have seen the effects of inflammation on the aging process in HIVer's and have called it an "aging disorder" for many years. It reinforces the need for healthy diet and healthy exercise with a healthy lifestyle. In my experience those addressing these factors have the best patient outcome. Thanks for bringing the science to the public-Scott Berliner R.Ph. Clinical Integrative Pharmacist at Friends in Deed, N.Y.C.
Comment by: Dr. Bob's Ask the Experts forum
Mon., May. 10, 2010 at 5:42 pm EDT
Hey everyone, it seems Dr. Bob has answered some recent questions on his forum related to the contents of his blog. Check out the Q&A's on the pages listed below:
http://www.thebody.com/Forums/AIDS/Fatigue/Current/Q208481.html ("aspirin for inflammation?")
http://www.thebody.com/Forums/AIDS/Fatigue/Current/Q208398.html ("Vocal chord inflammation the result of HIV?")
http://www.thebody.com/Forums/AIDS/Fatigue/Current/Q208393.html ("Inflammaging: Which tests are necessary?")
Comment by: Dave D
Sun., May. 9, 2010 at 11:14 am EDT
Hey Dr. Bob,
Please pontificate on the nitty gritty immunologic details, I'm a bit of a nerd and would really be interested.
Comment by: 55yo-diag2006-atripla2009-adherent-undetectable
Sun., May. 9, 2010 at 12:56 am EDT
thank you Dr Bob for yr interesting and timely article and for all the good work you do at theBody.com
since my diagnosis was in 2006 i did not benefit from the more agressive early treatment approaches and so the issues you address are perhaps of extra relevance.
as an informed amateur immunologist ( ?! ) i'd be happy to learn more of the technicalities, especially if we may find insights towards combatting the inflammaging process, and to the extent that you may help us understand some of the more esoteric numbers we see on our charts( including markers you mention here
not sure which forum to post to. .perhaps this area warrants its own as it cuts across meds/labs/living with hiv/complications . .
Viva your Mum.
Best regards n thanks again to all at the body
P.S. i linked to the cardio-vascular fact sheet below from the article about the DAD study. other readers in a similar situation to mine may find it useful.
Comment by: jeedah B.
Fri., May. 7, 2010 at 6:49 am EDT
It has been so many years that people waiting for vaccine but god forbid it will never happen due to inflamation and changing of the virus shapes and styles which affects the vaccine development scientist may they devlop a drug that will not siut one tpye of virus
Comment by: FMJ
Fri., May. 7, 2010 at 12:21 am EDT
My wife has had HIV since 1990 and each year, new and undiagnosed issues crop up for her. Articles like this help me think and pray for even more miracles than we've been given already. Thank you.
Thu., May. 6, 2010 at 9:23 pm EDT
My best wishes for your Mom's continued health and many thanks for concisely addressing this inflammatory/aging issue. I have been concerned about prematurely aging for several years now and it was satisfying to realize I had a pretty decent understanding of the subject matter after reading this blog. (While living in Boston, I was in the Smart Trial and had two treatment interruptions).
Please do take the time to detail more of the aging process at the celluar level. (I have more books on aging prevention than I did for my degree in engineering. And as you well know - there is a lot of snake oil out there.) Of course plenty of exercise, fruit, vegtables and sleep go a long way in slowing down the aging process, I have often wondered if the studies now going on regarding extending telemere length might help us virally-enhanced by 'reviving' prematurely aged CD8 cells that have been working overtime to keep the illness at bay while we suspended HARRT? And although somewhat unrelated, I would love to hear your thoughts on the concept of one pursuing a bone-marrow transplant and replacing one's blood with a virally resistant strain (as the German Hiver did) in an attempt to be fucntionally 'cured' of HIV. I of course realize this patient was suffering from invasive cancer and that surviving a bone marrow transplant comes with low percentages of success. But, if the HIV doesn't kill us, then the inflamation might. If cost were no concern and this in fact served as a cure, then it seems to me at least worthy of discussion.
I'll finish by saying that you have made me laugh again and again when reading your wit and for that I offer my sincere thanks and appreciation! Blog-on!
Comment by: DaphneeL.
Thu., May. 6, 2010 at 1:57 pm EDT
I am 20 yr. PWA and for at least TWELVE years I have KNOWN that I am aging way faster than my age group should. My doctor NEVER discusses this, OR runs the appropriate tests for baselines or age appropriate tests, complained many times. I AM SEEN AT DUKE UNIVERSITY, can u believe that Dr. Bob?
Finally AGING is being ACKNOWLEDGED as a REAL side effect, which none of my providers EVER would discuss or even consider a priority. Wish I lived on the WEST COAST. I am 51 and losing my mind's abilities but whatever, soon I guess it won't matter anymore. Take care there and enjoy everything.
Comment by: SotCharles
(Los Angeles, CA)
Thu., May. 6, 2010 at 1:24 pm EDT
I admire your turn about on AIDS. Far too many people beleive that HIV no longer causes chronic illness because of the potent anti-retrovirals available. I have early onset dementia caused by my 26 years of infection with HIV. I can no longer handle either physical or emotional stress without profound loss of muscle control, muscle weakness, and tremors. My reaction times to physical or intellectual stimuli are very slow. As I type this response, my hands are shaking and my head is trembling.
I worked for twenty years in a fast paced, demanding job that I genuinely loved. Through my work, I made a diffference in the lives of many people; and, I look back upon my career with satisfaction. My condition forced me to retire on disability two years ago. The decision to retire was the most wrenching decision of my life.
People have to know that HIV infection remains a very serious diagnosis. They shouldn't take the risk of infection lightly. The rising incidence of bareacking in the gay community concerns me very much. Perhaps if the effects of long term HIV infection were more widely known, fewer people would expose themselves to infection via barebacking.
Those of us who lived through the gay holocaust of the eighties and nineties have a responsibilty to the dead to see that new HIV infection among our gay brothers is halted. I wonder sometimes what my life without HIV would have been; but, I have had HIV for half my life and can't imagine what my life would have been without the virus.
In a way, HIV is a gift that has changed my life. I am more aware of every day and take pleasure in small things like a beautiful spring day or the smell of freshly turned earth. HIV has also been a curse that has left me with guilt that I survived when none of my friends did. I should have died a long time ago. The universe seems to have other plans for me. As I write about the gay holocaust, I hope that people see what a dread disease AIDS is.
Comment by: Ále
Thu., May. 6, 2010 at 1:10 pm EDT
I totally disagree with the relation between the rise of the Tea Party Movement with inflammation.
The rise of the Tea Party Movement is related to the lack of affordable or generic Viagra in this country.
Comment by: Jerry
(San Bernardino, CA)
Thu., May. 6, 2010 at 1:03 pm EDT
I love reading your articles, Dr. Bob, but why must you keep bashing us Tea Baggers? I am conservative and don't like the government wasting my $ and all up in my business. (TEA PARTY = Less government control & wasteful spending, less taxes, MORE POWER TO THE PEOPLE!!!)
Thanks, Dr. Bob, Love ya! ;)
Comment by: Marco A.
(Recife, PE, Brazil)
Thu., May. 6, 2010 at 12:56 pm EDT
What we can do? IÂ´ve 62 years, HIV+ since 1991.
Can I take some help from natural medicine?
Please, give us an hope.
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Life, Love, Sex, HIV and Other Unscheduled Events
Bob Frascino, M.D., was President and Founder of The Robert James Frascino AIDS Foundation. He had been an outspoken, popular expert in TheBody.com's "Ask the Experts" forums on safe sex and fatigue/anemia since 2000. Once a Fellow of the American Academy of Allergy, Asthma, and Immunology, and the American Academy of Pediatrics, Dr. Frascino served as Associate Clinical Professor of Medicine, Division of Immunology, Rheumatology, and Allergy, at Stanford University Medical Center from 1983 until 2001. He was a member of the American Academy of HIV Medicine and had also been a distinguished member of the executive boards of numerous state and regional associations.
We're inexpressibly saddened to share the news that Dr. Frascino passed away unexpectedly on Saturday, Sept. 17, 2011. Click here to read more and to share your thoughts.
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October 19, 2011 - The Ultimate Unscheduled Event: A Blog Entry by Steven M. Natterstad, M.D.
September 23, 2011 - HIV Guidelines: Some Evolve; Some Don't. What's Up with That? Part Two -- A Blog Entry by Bob Frascino, M.D.
August 25, 2011 - HIV Guidelines: Some Evolve; Some Don't. What's Up With That? Part One: A Blog Entry by Bob Frascino, M.D.
July 27, 2011 - Three Decades of HIV/AIDS, Part Three: A Blog Entry by Bob Frascino, M.D.
June 30, 2011 - Three Decades of HIV/AIDS, Part Two: A Blog Entry by Bob Frascino, M.D.
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