HIV Actually Appears to Have Strengthened, at Least in Europe

HIV Actually Appears to Have Strengthened,

 at Least in Europe

HIV’s virulence seems to have gathered steam over time, according to a large study of the epidemic in Europe, aids map reports. This finding is in direct contrast to a small study conducted in sub-Saharan Africa that made headlines on World AIDS Day. Publishing their findings in The Lancet, researchers in the pan-European CASCADE study of 15,875 people with HIV examined key viral and immune system markers between 1979 and 2008 to analyze how the virus has adapted and changed throughout the population.

The researchers found that the average time individuals took to see their CD4 levels fall below 350 after contracting HIV has fallen from 7 years for those who seroconverted in 1980 to 3.4 years for those who did so in 2002. The estimated CD4 count following seroconversion was 770 in 1979 and 570 in 2002, indicating that HIV’s acute phase appears to have become more destructive to the immune system. The average viral load set point—the level at which the virus replicates following the acute phase spike—rose from 11,200 in 1980 to 31,000 in 2002. It appears there was a decline to 25,500 in 2008, however.

These findings suggest there is greater urgency to “test and treat” people for HIV, as the slogan goes, since people who contract the virus have a smaller amount of time before HIV disease progresses significantly. Treating the virus as early as possible would also yield significant benefits for prevention of the virus, since the higher viral set point means that untreated HIV is 44 percent more infectious on average.

While the African trial may be flawed because the study was so small and compared only two time points, it is also possible that both studies’ findings are valid. Because antiretroviral (ARV) treatment was introduced in sub-Saharan Africa more recently, African HIV may have evolved to favor less virulent strains that did not kill “hosts” before they could pass on the virus. In Europe, ARVs may have shaped the evolution of the virus such that strains that replicate more rapidly in the absence of treatment are more likely to get passed on, since once people go on treatment the chance of transmission plummets.

To read the aidsmap story, click here.

To read The Lancet abstract, click here.

Search: HIV, virulence, Europe, CASCADE, The Lancet.

Story can be found here: http://www.poz.com/articles/epidemic_virulence_761_26590.shtml?utm_source=newsletter12_18&utm_medium=TJI1&utm_campaign=treatment

Don’t believe the hype – we are a long way from an HIV cure

AUTHOR

1. 

   Timothy P Lahey

   Associate professor of medicine at Dartmouth College

DISCLOSURE STATEMENT

Timothy P Lahey does not work for, consult to, own shares in or receive funding from any company or organisation that would benefit from this article, and has no relevant affiliations.

The Conversation is funded by Howard Hughes Medical Institute, Robert Wood Johnson Foundation, Alfred P Sloan Foundation and William and Flora Hewlett Foundation. Our global publishing platform is funded by Commonwealth Bank of Australia.

Effective treatment, but no cure yet. Chaiwat Subprasom/Reuters

HIV has infected over seventy million people but only one of them has been cured: Timothy Ray Brown.

An HIV-positive resident of Berlin, Germany, Brown developed relapsed leukemia in 2006. To treat the leukemia, he underwent special bone marrow transplants that also rendered him genetically resistant to HIV. Brown’s HIV medications were stopped in 2007 and several years later he remains free of HIV.

Brown is historically unique but in recent years scientific journals and the popular press alike have published multiple claims of HIV cures.

In 2012, French scientists announced a “functional cure” of HIV when 14 patients who were treated within months of initial HIV infection remained clinically stable after treatment stopped. Similarly mild cases of HIV disease had been reported even in untreated patients, and unlike Brown the French patients still have detectable HIV in their bodies. Thus the French researchers likened a fairly common piece of good clinical fortune to a historically important cure, and added little more than confusion in the process.

Timothy Ray Brown, the ‘Berlin patient.’ Kevin Lamarque/Reuters

Click to enlarge

The same year Boston researchers announced that two HIV patients with cancer had undergone standard bone marrow transplants on HIV therapy, and afterward had unusually low levels of HIV in their blood. Preeminent scientists said it was “conceivable and maybe even likely” the Boston patients' HIV was gone, HIV medications were stopped, the virus rebounded, and several months after it started the Boston celebration came to an end.

In March 2013, doctors announced that an HIV-exposed baby from Mississippi who was treated within hours of exposure was considered cured as once-detectable HIV could no longer be found off of therapy. Scientists speculated HIV never gained a foothold in vulnerable immune cells. In July 2014 it was reported that the Mississippi baby relapsed, most likely because the virus had been lurking all along in those self-same cells.

Echoing the Boston experience, this year two Australian patients were called “HIV-free” and “cleared” of HIV after very low levels of the virus were detected in the blood after stem cell treatments. Both men remain on HIV therapy “as a precaution” so there is no definitive proof of anything more than highly effective therapy and an intense hunger to claim something approximating a cure.

None of these patients, with the exception of Brown, was cured of HIV. Yet in each case a cure has been claimed or the words used to describe the story were so similar to “cure” as to be indistinguishable to the untrained reader.

Why?

Desperation, for starters. HIV has killed over 39 million people so far and every year more than a million more are infected. There is no more urgent public health priority than the discovery of an HIV cure. As a result, when new and exciting HIV findings emerge scientists and journalists can abandon their usual caution and succumb to the temptation to use words like “cure” loosely.

We can’t afford to be complacent about HIV. Konstantin Grishin/Reuters

Even cool headed researchers are keenly aware that generating buzz can be the difference between generous funding or the closure of their labs. Salesmanship can devolve into exaggeration as the press conference begins. Journalists and editors, too, are tempted to generate more clicks and sell more papers by freeing the results they report from the scientists’ humdrum caveats.

Desperation and salesmanship aside, even the brightest and most cautious scientists and journalists can get fooled. Many honestly believed, for instance, that the Mississippi baby was free of HIV.

Whatever their motivations, premature intimations of a cure can be dangerous.

The credibility of the HIV research effort is undermined when retractions follow each exciting new announcement of a cure (or whichever phrase like “cleared" is that day’s facsimile). The confusion and skepticism created by repeated retractions can dampen research subjects’ enthusiasm to enroll in studies and even weaken research funding.

The intimations of a cure can also lead to complacency about HIV. Reducing HIV risk behaviors is always challenging, and it is harder when the potency of HIV treatments or the near-availability of an HIV cure make HIV infection seem like, as one newly-diagnosed man told me, “no big deal.” Modern treatments for HIV do keep millions alive for decades and we are closer to a cure than ever before but nonetheless HIV is most definitely a very big deal.

To preserve our scientific credibility, and support our prevention efforts, we should put the word “cure” on a shelf and let it gather a little dust. Someday, when we finally find a cure, a real-life, honest to goodness, checked and double-checked cure, then we can dust off the “C” word and let Timothy Ray Brown know at long last he can have some company in the world’s most elite club.

Until then, we should remember Margaret Heckler. As the Secretary of Health and Human Services, she helped announce Robert Gallo’s discovery of the HIV virus in 1984. Famously she concluded by predicting that we would develop an HIV vaccine within two years. Thirty years later our patients still don’t have an HIV vaccine, or a cure. The next time the lights go up and the microphones click on, let us remember that the way we celebrate progress today cannot forget the unfinished work we take up first thing tomorrow. 

1. 
   

The Sooner, the Better for HIV Treatment

A new study shows that starting antiretroviral drugs within a year of detecting the virus decreases patients’ chances of developing AIDS. But many people who are infected don’t know it yet.

 

Nick/Flickr

“Two critically important issues in human immunodeficiency virus (HIV) therapeutics are when to start antiretroviral therapy and how well these medications restore immunity,” writes Dr. Timothy Schacker of the University of Minnesota in a recent issue of JAMA Internal Medicine. He is commenting on a study done by the National Institutes of Health, also published in that issue, that looked at when HIV patients started taking antiretroviral meds, and how that correlated with their immune health later.

The researchers studied the data of more than 1,000 patients enrolled in the U.S. Military HIV Natural History Study between 1986 and 2010. They noted how soon patients started taking antiretrovirals after seroconversion—the point after HIV infection at which antibodies to the virus can be detected in a person’s blood. To measure immune health, the researchers looked at patients’ levels of CD4 T-cells—a kind of white blood cell. When people taking antiretroviral medication see their CD4 counts increase to 500 cells per microliter of blood, that is “typically regarded as optimal immune recovery,” the study says.

But it’s not perfect. According to the study, in healthy, HIV-negative people, that count is more like 900 cells per microliter. So HIV-positive people whose CD4 counts are higher than 500 but lower than 900 cells per microliter could still have a less-than-ideal immune system and be at increased risk for developing AIDS, even if they’re taking the drugs. So for the purposes of this study, 900 cells per microliter was seen as the ideal target that doctors should shoot for when treating patients using antiretrovirals.

Starting antiretroviral treatment within a year or less of seroconversion was associated with better outcomes for the patients, especially if their CD4 levels were at least 500 cells per microliter when they started treatment. These people had a higher chance of getting to the 900 cells per microliter “normal” level and were subsequently at lower risk of developing AIDS. This wasn’t a guarantee—only about a third of patients who started the medication within a year of seroconversion reached normal CD4 levels.

Early intervention might also be easier said than done. According to the Centers for Disease Control and Prevention, one in five people with HIV in the U.S. don’t know they have it. When the infection is still new, they might not be symptomatic, or they may mistake their symptoms for something else. What’s more, only one in three adults, and one in four children, have access to antiretroviral medications.

“The importance of a public health strategy that includes frequent HIV testing in persons at risk and prompt initiation of [antiretrovirals] after diagnosis is underscored by [these] two findings,” the study reads.

In his commentary, Schacker notes that while this research shows a step that can be taken to increase some HIV patients’ health, it’s far from a perfect treatment protocol.

“Even if we were to accept a score of only one-third of persons as a success, it is unrealistic to think that we will routinely identify patients within 12 months of infection, especially in the parts of the world where this disease is most prevalent,” Schacker writes. “This sobering observation underscores the need to better understand the pathogenesis of HIV infection and use that information to inform drug discovery and rational policies for treatment.”

This article is from my friend PositivelyJeffrey's Blog: http://positivelyjeffrey.com/2014/12/04/sooner-better-hiv-treatment/

World AIDS Day December 1, 2014

World AIDS Day December 1, 2014

As I sit here thinking about another year coming close to an end with World AIDS DAY knocking on our door, I can help but think how blessed I have been the past 6 years of my life.

I know my journey has not been as long and tiresome as the many who have endured the AIDS epidemic now for 30 plus years. I have so much respect for those who have endured PROMISE after PROMISE, HOPE after HOPE of a CURE for this HORRIFIC DIESEASE. I know that for so many of the wonderful people I have met online through social media (Dab Garner, Shelby Welchel, Maria Mejia, Jeremy Scott Hobbs, Timothy Ray Brown, Bob Bowers, Kevin Maloney) and the list goes on, the journey living with HIV/AIDS has not been a pleasant experience. These wonderful people along with so many others have fought for years not only to live, but they have fought for our rights to have the medical care that we receive here in AMERICA. Without people like these individuals fighting government, making statements and teaching others about the medical needs of those affected by HIV/AIDS we could not continue to enjoy getting the medical care needed to fight.

I have learned in the past 6 years being Positive that you can NOT make it on YOUR own. WE all need each other. We all need someone who “HAS BEEN THERE”, to help us understand the why’s and how’s when it comes to dealing with a DISEASE like HIV/AIDS. I have been so blessed and honored to get to know the people who “HAVE BEEN THERE”… Those people are LOVING and CARING and WANT to SHARE!! Those people want others to LISTEN and take NOTE so they DO NOT HAVE TO GO THROUGH THE SAME THINGS.

If I would have LISTENED and HEEDED the WORDS of the GREAT PEOPLE I have met in the last 6 years ~ BEFORE I BECAME HIV+ ~ I WOULD NOT BE HIV+!!!!!!

The message

 ~ AS SIMPLE AS IT CAN BE ~

~~

IF YOU RESPECT YOURSELF

PROTECT YOURSELF

PRACTICE SAFER SEX!!!

~~

It can be told in many languages but it all boils down to those simple words. If you care enough about yourself, you will protect yourself from the spread of HIV/AIDS.

~YES~

 ~ SEX is NATURAL~

 ~ SEX is FUN~

~ Unprotected SEX CAN = HIV/AIDS ~

HARSH BUT TRUE!!!

HIV/AIDS is NOT FUN!!!

Popping pills everyday that make you sick, that are highly toxic, and can have adverse side effects on your body is NO WAY to spend the rest of your life. ASK ME ~ I KNOW!! ASK ANYONE who is HIV+ and they will tell you the same. The PILL LOAD only increases the LONGER you live with HIV/AIDS. They do NOT tell you that in the “CUTE” little T.V. Commercials!! ASK A SURVIVOR ~ THEY WILL TELL YOU THE TRUTH!!

HIV/AIDS SUCKS!!!!

~ SO my point this “WORLD AIDS DAY” ~

RESPECT YOURSELF

~~

PROTECT YOURSELF

~~

PRACTICE SAFER SEX

We can put an END to HIV/AIDS – IT will take everyone doing their part to PRACTICE SAFER SEX until this DISEASE is wiped out!!!

God Bless you all,

David A. Moorman

Dab Garner

Posted on November 20, 2013 by A&U in Features

Share on facebookShare on twitterShare on emailShare on pinterest_shareMore Sharing SerReal-Life Teddy Bear

Real-Life Teddy Bear

Diagnosed with AIDS at a time when it was still called GRID, cuddly advocate and long-time survivor Dab Garner is still going strong in the fight against HIV/AIDS
Text & Photos by Sean Black

Dab Garner, founder and CEO of Dab the AIDS Bear Project, and an aggressive ally for the rights and health of others, points to the right cheek of his ruggedly handsome face; a face that bares no apparent signs of his many years living with HIV and the struggles and losses he has endured.

“Her little mouth was on the side of her face, her ear was over here,” he begins, describing Candace, a crack-addicted infant born with HIV along with a number of heartbreaking physical deformities and challenges as a result of fetal alcohol syndrome.

“She couldn’t hear out of it. She was constantly sick and small for her size.” His voice breaks and tears begin to trickle from the corners of his piercing eyes. Remembering the baby girl who helped bring him into his lifelong fight against AIDS, back in 1985, he notes that Candace was one of the earliest known cases of mother-to-child transmission. The daughter of a troubled woman who died shortly after her birth, Candace entered as her mother exited a world that had already been forever changed.

Navigating mountains of red tape and unable to legally adopt, Dab and his second partner, Brad, both living with HIV and unsure of there own precarious health conditions, were finally able to bring Candace home from the hospital. With a life expectancy of only several months and round-the-clock needs, life wasn’t easy for the ailing child nor was it for her new “godparents.” But, the loving and non-conventional family endured. Dab, a full-time college student and professional model, whose work opportunities were waning after he was publicly named in the press as being infected with HIV (more than a decade before the HIPAA Privacy Rule), and Brad, a San Francisco police officer, received an enormous amount of help from friends; mostly those belonging to a community he still holds sacred to this day.

“My leather group was the only group that really didn’t treat me any differently.” Recognizing the individuals who stepped up to help him and his lover through this difficult time, Dab recalls many by name. “There was Vicky, Vivian, Marilyn, Liz, Terri, Allison, Carol, Ben, Alex, Randy, Marshall, Andy, Bill, James, Jack, Sandra, and Tina. Oh, and Olivia and Sheila who were lesbian leather lovers,” Dab smiles as we acknowledge the playful sounds and alliteration of his words.

Looking back to the cold month before his twentieth birthday, in the winter of 1982, when he had just been diagnosed with PCP and GRID, a familiar nightmare began to repeat itself. “I don’t think I had ever been so scared in my entire life. I just watched two people, who I loved, die alone in those rooms.” Losing loved ones at such an early age was new for Dab and many others at this troubling time. His losses were that of his best-friend Michael, and his first boyfriend Derek, a successful fashion photographer and the reason for his move to San Francisco, just days after graduating from high school. The “Motherland” he sought after leaving his rigid Pensacola roots was slowly sinking around him. After three weeks of his terrifying ordeal, Dab started getting better and was eventually released with the intervention and aid of legal action. “Friends had to get a lawyer to get me out of that room.”

Having to watch Derek and Michael suffer and die alone in isolation upset and angered Dab. “It broke my heart that I could not go into the room to show them love and to comfort them.” Dab took action. “I pondered what I could do to make them feel love since the doctors and nurses wore protective garments restricting any form of human touch. So being a hairy, gay man [i.e., a bear], I decided to give them a teddy bear with a note saying how much I wished I could be in there with them, to hold them, and to let them know they were very much loved.”

While he was in quarantine, Dab made friends with a nurse named Vicky. Taking a large risk by disclosing patient information, she would let him know when someone with AIDS came into the hospital and was placed in similar scary confines. “Even though I might not personally know them, I would go get them a bear so that I could at least let that person know that someone cared about them.”

Dab started helping others and talking about HIV on a broader spectrum at that time, beginning with one of the first international conferences on HIV/AIDS, held in Paris, and attended by over 2,800 people. Dab remembers that French virologist Dr. Luc Montagnier, who won the 2008 Nobel Prize for his co-discovery of HIV was presenting. Dab also attended the first AIDS candlelight vigil held in San Francisco while a similar one was being conducted in tandem in New York City. Extending his voice as more opportunities availed themselves through early fundraising venues such as the AIDS Walks, bicycle rides, LGBT Pride festivals, health fairs, men’s and women’s events, high schools, conferences, he continued speaking openly about his disease.

Dab also got involved in organizations like the AIDS Coalition to Unleash Power (ACT UP) and began making trips to our nation’s capital, which he still does, on a regular basis. Further continuing his legacy of love today, Dab estimates that he presents at more than 150 events each year. “Pretty much anywhere they will put a microphone in my hand,” he attests proudly. In addition, Dab has amassed an army of caring soldiers, 509 to be exact, over the last thirty-two years. Called Ambassadors of Hope, these individuals, who reside in twenty-three countries, spread messages of hope, compassion, and love for people living with HIV while taking pictures with their bears. “Dab the AIDS Bear isn’t just one individual, it’s a collective team of people—activists, community leaders, members of organizations, students, celebrities and every day citizens,” he humbly shares.

Pausing to take a reflective breath, he concludes with how he got his nickname. “Candace had a really bad lisp when she would talk. So when she tried to say the word ‘Dad,’ it came out ‘Dab.’ When my friends heard this, they all thought it was so adorable, so from then on I became ‘Dab.’” After a way too short life, Candace lost her battle to AIDS on August 14, 1989, at the age of four. As this little angel was dying, her “Dab” made a certain promise to her, to which he has held true, to this day—making other children like her feel special and loved.

◊

For more information about how to help the Dab the AIDS Bear Project this holiday season and all year long, link to Dab’s entry in our Holiday Gift Guide or log on to www.dabtheaidsbearproject.com.

Sean Black is an Editor at Large for A&U.

You can find this story here: http://aumag.org/wordpress/2013/11/20/dab-garner/

Matters of the HEART {Part 2}

Prevention and Management of HIV-Associated Cardiovascular Disease

By Theo Smart

From TheBodyPRO.com

November 17, 2014

 

"Our understanding of mechanisms of HIV-associated cardiovascular disease (CVD) has not yet translated into tailored clinical interventions," says Virginia Triant, M.D., M.P.H., of Massachusetts General Hospital. Triant provided a state-of-the-art presentation on cardiovascular complications in people living with HIV at IDWeek 2014.

The first article in this series covered the context and causes of HIV-related CVD. This second article focuses on how healthcare providers can integrate the prevention and management of CVD into HIV chronic care -- addressing both the traditional risk factors of CVD, and other risk factors that are HIV-specific.

Estimating Risk

Part of the challenge for clinicians is that it is unclear to what extent general population guidelines can be applied in the management of CVD in people living with HIV.

It isn't clear that any of the available tools to predict CVD risk in the general population underestimate risk in HIV. For instance, the Framingham risk score (FRS) was found to underestimate risk of AMI (acute mydocardial infarction) and stroke in people living with HIV on antiretroviral therapy in the D.A.D study and stroke in the Multicenter AIDS Cohort study.

However, new cardiovascular risk guidelines from the 2013 American College of Cardiology/American Heart Association (ACC/AHA) have added some complexity to HIV-specific risk prediction. These guidelines employ new CVD risk prediction equations -- the pooled cohorts equations (PCE). There have been reports that they may overestimate risk in the general population but they also appear to underestimate risk in people living with HIV.

Furthermore, the Framingham risk score and ACC/AHA guidelines do not seem to be in complete agreement about which people living with HIV are at low or high risk of CVD -- with discordant results in about 17% of cases.

Triant suggested that clinicians should consider calculating both the Framingham risk score and the ACC/AHA risk score.

Patients who are in a high-risk category by at least one score (greater than 10% for FRS and greater than 7.5% for ACC/AHA) merit:

• Suppressive antiretroviral therapy, if not already treated
• Strong consideration of statins
• Aggressive CVD risk-factor reduction

Management of Dyslipidemia in HIV

Some questions about the ACC/AHA guidelines remain. Rates of dyslipidemia are much higher in people living with HIV than in control patients, with a distinctive pattern of low high-density lipoprotein (HDL) and high triglycerides. Although statins are the main treatment, dyslipidemia may be more difficult to treat in people living with HIV, and the effects as well as drug interactions with antiretroviral drugs need to be considered.

In patients living with HIV, the use of statins has been shown to effectively lower low-density lipoprotein (LDL). Data presented at CROI 2014 also suggested that statin use may also decrease immune activation, and contribute to immune reconstitution independently of antiretroviral therapy. In addition, in at least one observational cohort, statin use was associated with significantly decreased mortality in people living with HIV who were on suppressive antiretroviral therapy.

There are controversies, however, regarding the approach to treating cholesterol recommended by the 2013 ACC/AHA cholesterol treatment guidelines. These recommend statin initiation in four major benefit groups:

• Those with clinical atherosclerotic cardiovascular disease (ASCVD)
• LDL ≥ 190 mg/dL
• Diabetes age 40-75
• Estimated 10-year ASCVD risk ≥ 7.5%

In contrast to the past, the guidelines set no LDL treatment targets and recommend no non-statin therapies. Using the new risk calculator (the PCEs) to estimate 10-year ASCVD risk, the guidelines recommend substantially increased statin treatment in general population -- with 12.8 million additional adults eligible for statin therapy (mostly among older patients without cardiovascular disease).

They also recommend significantly increased statin use in people living with HIV without traditional risk factors for CVD -- despite the fact that people living with HIV have a different typical cholesterol profile and for whom the mechanism of CVD is different. At present, there is not much evidence of efficacy and safety from randomized clinical trials for treating people living with HIV at risk as determined by the new ACC/AHA risk calculator and the guidelines statin intensity definition is not directly applicable in this population.

Nevertheless, Triant believes it is likely that that statins will be effective in the risk groups outlined by guidelines. The question might rather be, "Do they go far enough?" Even using both Framingham and PCE risk calculation, the risk of CVD appears to be underestimated in HIV, and there is a chance that a larger segment of the population living with HIV may benefit from statins. Future research will address some of these gaps.

In the meantime, on the basis of the available guidelines and published data on the use of statins in people living with HIV to date, Triant recommended the following clinical strategy for the management of dyslipidemia in HIV:

• Check fasting lipids
  • At HIV diagnosis
  • Prior to and within 1-3 months after starting or changing antiretroviral therapy
  • Every 6-12 months
• Consider starting statins based on ACC/AHA cholesterol guidelines
• Consider therapy with:
  • Statins, if LDL is above ATP-III (adult treatment panel) goal, or TG (triglyceride) is between 200-500 with elevated non-HDL
  • Fibrates, if TG > 500
• 2013 HIV primary care guidelines include detailed statin-antiretroviral interaction chart

Management of HIV-specific CVD Risk Factors

In addition, CVD risk in HIV disease may be reduced by targeting HIV-associated inflammation and immune activation using established anti-inflammatory therapies (such as aspirin), antiretroviral therapy or novel immunomodulatory agents, according to Triant.

Aspirin, which is commonly used to reduce CVD from traditional risk, may also have potential reducing CVD in HIV disease, but studies suggest that aspirin is dramatically underused by people living with HIV who meet the traditional CVD-risk criteria. One paper reported that 31% of people living with HIV met the criteria for using aspirin to reduce CVD risk, but only 1.6% were receiving it. A reasonable clinical strategy, however, is that anyone with low bleeding risk who has known CVD or a high predicted CVD risk, should be taking aspirin.

There are also data to show that aspirin can decrease immune activation and platelet activation in people with HIV but whether it should be used more widely to prevent AMI or stroke in people living with HIV who don't meet the usual criteria for CVD is unclear.

"Interventions targeted at HIV-specific inflammation and immune activation may better reflect pathogenesis and reduce CVD," said Triant.Antiretroviral therapy, may help since the most direct intervention would be treating the virus itself. Although the START trial will be the first randomized clinical trial to look at the rates of comorbidities including CVD in patients started on early versus deferred antiretroviral therapy, there has already been a paradigm shift in the role of treatment in relation to CVD risk in HIV.

"The CVD-related benefit from virologic suppression and immune reconstitution achieved by treating HIV are thought to outweigh possible proatherogenic effects of individual medications," said Triant.

This change has been reflected in current HIV treatment guidelines. For instance, in 2010, the IAS-USA HIV treatment guidelines, recommended the initiation of antiretroviral therapy specifically for patients with high cardiovascular risk regardless of CD4 count; and the current DHHS HIV treatment guidelines, recommend antiretroviral therapy for all people living with HIV based upon the "growing awareness that untreated HIV infection or uncontrolled viremia may be associated with the development of many non-AIDS defining diseases, including cardiovascular disease (CVD), kidney disease, liver disease, neurologic complications, and malignancy."

So the clinical strategy is now to treat HIV to reduce inflammation, immune activation, and associated cardiovascular risk, but to consider underlying CVD risk when selecting specific antiretroviral medications that may have varying risk.

However, there appears to be a limit to this strategy as treatment intensification seems to have little or no effect in patients who already have suppressed viral loads. For instance, recent studies have found that when raltegravir (Isentress) was added to suppressive treatment, there was no effect on either flow mediated dilatation (FMD) or markers of viral replication.

Novel interventions, immune-modulators, such as using maraviroc (Selzentry, Celsentri) may be an exception to this rule, by virtue of its activity as a CCR5 antagonist, rather than as an antiretroviral. Recent papers in the literature explore its theoretical role in preventing/delaying atherosclerosis, andone study in mice found that maraviroc reduced the atherosclerotic progression by interfering with inflammatory cell recruitment into plaques suggesting that it could have a potential cardioprotective effect in HIV.

Similarly, Triant believes a number of older immune-modulators may have potential for reducing CVD risk in people living with HIV. These include methotrexate, which has been reported to decrease CVD risk in the general population. A randomized controlled trial is currently underway to assess the effect of low-dose methotrexate on inflammatory markers and endothelial function in HIV-positive patients on suppressive antiretroviral therapy. Meanwhile, current data on other immune modulators has been mixed.

Managing Traditional Risk Factors

The other key strategy for fighting CVD in people living with HIV is to manage traditional CVD risk factors (e.g. smoking, diabetes and hypertension) aggressively.

People living with HIV on suppressive ART may lose more years of life due to smoking than HIV.

Triant's recommended clinical strategy for smoking cessation:

• Apply guidelines for general population to all HIV smokers:
  • Routine screening integrated into HIV primary care
  • Strong, brief, intensive repeated counseling
  • Pharmacologic interventions (varenicline is safe and effective in HIV)
• Consider systematic approaches to identify HIV smokers and ensure smoking cessation interventions are applied

Diabetes and Hypertension Management

Additionally, Triant suggests using the follow strategy to monitor and manage diabetes and hypertension:

• Check fasting glucose or HbA1C (glycated hemoglobin) at HIV diagnosis, 1-3 months after starting or changing treatment regimen, and every 6-12 months thereafter
• Check HbA1C every 6 months in patients with diabetes
• Diet and exercise intervention recommended:
  • Shown to decrease HbA1C for HIV patients
• Check blood pressure annually
• Follow existing 2014 Hypertension Guidelines for general population
  • No HIV-specific guidelines

Consider drug-drug interactions

• Use of some calcium-channel blockers contraindicated with protease inhibitors

Discussion

Many questions remain regarding the optimal management of CVD risk in people living with HIV, such as whether to use statins more broadly, whether immune-modulators will work and whether CVD prevention strategies should be the same in HIV-infected women and patients in resource-limited settings?

However, it is clear that clinicians should build CVD risk assessment into their clinical practice, start statins in those who qualify, have a low threshold for diagnostic work-ups in their patients living with HIV, treat HIV and manage traditional CVD risk factors.

"The intensity and consistency of HIV care provide opportunities to prevent and manage chronic disease complications," Triant concluded.

Read Part 1 to review the context and pathophysiology of cardiovascular disease in people living with HIV.

Theo Smart is an HIV activist and medical writer with more than 20 years of experience. You can follow him on Twitter @theosmart.

Copyright © 2014 Remedy Health Media, LLC. All rights reserved.

This article is from thebodypro.com - http://www.thebodypro.com/content/75245/prevention-and-management-of-hiv-associated-cardio.html?getPage=1

Matters of the HEART {Part One}

Cardiovascular Complications in Patients Living With HIV

By Theo Smart

From TheBodyPRO.com

November 17, 2014

With the rise of heart disease as one of the leading causes of death globally, clinicians should anticipate a significant impact of cardiovascular disease (CVD) in people living with HIV. However, in the case of HIV disease, "the pathophysiology of CVD is driven in large part by HIV-related immunologic and inflammatory changes, and current CVD prevention paradigms do not reflect this pathophysiology," according to Virginia Triant, M.D., M.P.H., of Massachusetts General Hospital.

Triant gave a state-of-the-art presentation on cardiovascular complications in people living with HIV at IDWeek 2014 in Philadelphia. This article focuses on what is now known about the context and pathophysiology of cardiovascular disease in people living with HIV -- as the understanding of these complications has evolved considerably in recent years.

The second article in the series will focus on how healthcare providers can integrate the prevention and management of CVD into HIV chronic care -- addressing both the traditional risk factors of CVD, and other risk factors that might be HIV-specific.

Context of HIV and CVD

Aging-associated non-communicable comorbidities such as hypertension, myocardial infarction, peripheral arterial disease and impaired renal function are significantly more prevalent among people living with HIV than HIV-negative people.

Several large cohort studies have found an increased risk of acute myocardial infarctions (MI) and coronary heart disease (CHD) in people living with HIV. A study that Triant presented at CROI 2014 found an elevated relative risk of major adverse cardiac events (MACE), which included myocardial infarction, stroke, angina and coronary revascularization, in people living with HIV than in HIV-negative people, across gender and age groups. The risk was increased even among those who traditionally would have been considered to be at low risk for heart disease -- which may reflect "the different distribution of CVD risk factors in HIV, with important contributions from non-traditional risk factors reflecting HIV-related immune dysregulation."

Since the advent of antiretroviral therapy, CVD has become a major cause of mortality in HIV disease --although management practices in recent years may have lowered CVD-related mortality in the D.A.D cohort. Still, it remains the third most frequent non-AIDS-related cause of death amonth HIV-positive women.

Pathophysiology of HIV and CVD

Ever since the heightened risk of CVD began to be recognized in people living with HIV, the understanding of its causes has been evolving. A number of the traditional risk factors, such as smoking, which is far more common in people living with HIV than in HIV-negative individuals, played a role. However, these were found to only account for around 10%-25% of the heightened risk in large cohort studies.

Then much of the blame was placed on antiretroviral therapy, in particular, certain drugs, includingselect protease inhibitors and possibly abacavir (Ziagen). For instance, in the D.A.D. study, which was a prospective cohort study with 33,347 subjects, the relative risk of acute MI was 1.16 per year -- but the increased risk was seen on protease inhibitor-based regimens and not non-nucleoside reverse transcriptase inhibitor-containing regimens.

But, again, there is a 40%-80% increased risk of acute MI that persists despite accounting for both established CVD risk factors and antiretroviral therapy use.

Today, "the persistently increased risk is thought to be driven by HIV-specific inflammation and immune activation," said Triant, "and this is supported by extensive data."

For instance, in the SMART study (comparing continuous antiretroviral therapy versus episodic treatment) there was an increased CVD event rate in the arm given episodic antiretroviral therapy vs. the arm given continuous treatment (P = .05). A subsequent analyses of the SMART study found that, at baseline, markers of inflammation, including high-sensitivity C-reactive protein, IL-6, and d-dimer, all strongly correlated to overall mortality; and that after one month of treatment interruption, and viral replication continued, both IL-6 and d-dimer levels increased.

In addition, the increased immune activation in people living with HIV appears to be linked with a number of markers of CVD. In the Women's Interagency HIV Study, there was increased immune activation in women living with HIV vs. controls without HIV. Among those living with HIV, having a higher frequency of activated T cells was associated with an increased prevalence of carotid artery lesions -- regardless of age, antiretroviral medications, or viral load.

One possible mechanism for the chronic immune activation (despite suppressed viral loads) is believed to be the mass bacterial translocation from the gut that occurs over the course of HIV infection. Lipopolysaccharides (LPS) released by these bacteria activate monocytes and macrophages, which, in turn, are associated with increased levels of soluble CD14 -- a biomarker of monocyte activation.

Recently, an analysis of ACTG 5078, documented that both LPS and sCD14 were elevated in people living with HIV and were associated with the development of subclinical atherosclerosis. This effect was independent of traditional CVD risk factors.

Another study has found that another monocyte/macrophage activation marker, sCD163, was elevated in men living with chronic HIV infection and low or undetectable viremia when compared to HIV-negative controls -- and was associated with non-calcified coronary plaques and arterial inflammation.

A subsequent study found that relatively young people living with HIV had an increased prevalence of plaque features that are highly vulnerable to acute rupture compared to HIV-negative individuals, which could be the reason for the heightened rates of MI's and sudden cardiac death.

People living with more advanced HIV disease -- as evidenced by low CD4 cell counts and high viral loads appear to be at higher risk. For instance, an analysis of the HIV Outpatient Study found that people living with HIV with CD4 counts below 500 were at an increased risk of CVD events independently of whether they had other known CVD risk factors or were on antiretroviral therapy. Similarly, another analysis of the Partners HealthCare System cohort, found that having a CD4 count below 200 was independently associated with AMI (acute myocardial infarction). In fact, having a low CD4 count was a more important factor than any individual antiretroviral medication with respect to increased risk of AMI or viral load.

But even though viral load was not an independent risk factor in the Partner's HealthCare System Cohort, an increased viral load was a predictor of AMI risk. Other studies have found that an increased viral load was linked to ischemic stroke events, and that a detectable viral load (viral load above 50 copies/ml) was associated with increased risk of myocardial infarction.

Similarly, an analysis of the 82,459 people living with HIV in the Veterans Aging Cohort Study Virtual Cohort from April 1, 2003, through December 31, 2009 found an increased AMI risk in participants with both detectable viral loads and CD4 counts below 200. But even in patients achieving virologic suppression, there was an increased risk of AMI in contrast to people who did not have HIV.

There seems to be some elevated risk of CVD in people living with HIV regardless of treatment, viral load or immunodeficiency. This has been shown in a study of cardiovascular risk in elite controllers -- people living with HIV who have low viral loads and are immunologically stable without treatment. Despite their status as non-progressors, they have increased carotid intima-media thickness -- a surrogate marker of atherosclerosis -- compared to HIV-negative individuals.

Therefore, HIV infection, regardless of treatment, CD4 count or viral load, is associated with some degree of immune activation and an increased risk of cardiovascular disease.

In conclusion, for people living with HIV, the increased risk of cardiovascular disease is multifactorial due to traditional risk factors, HIV-related immune activation and immunodeficiency, and antiretroviral therapy may increase the risk in some ways and decrease it in others. But this complexity is not yet accounted for in how the disease is being prevented or managed.

Read Part 2 to see how providers can integrate the prevention and management of cardiovascular disease into HIV care.

Theo Smart is an HIV activist and medical writer with more than 20 years of experience. You can follow him on Twitter @theosmart.

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This article is from thebodypro.com - http://www.thebodypro.com/content/75244/cardiovascular-complications-in-patients-living-wi.html?ic=700100