The published results from the HPTN 052 study as well as an increasing amount of talk around treatment as prevention have opened up a new avenue of questioning for HIV positive members of society.  Some think that having an undetectable HIV viral load means that you can’t transmit HIV to others.

Agreeing or disagreeing with this mindset is not easy and takes a lot of information.

Although it is documented that the subjects of 052 with an undetectable viral load did not transmit HIV, lets not forget that all the study participants received prevention counseling that included free condoms.

Where they used? Who knows?

Nothing in life is 100% risk free.  Getting out of bed in the morning comes with some amount risks.

A case study from Germany involving a 39-year-old man in a monogamous relationship, on ART since 2000, with a viral load <50 copies/mL over a period of over 4 years.  The patient was in good health, good treatment adherence and no other STIs.  In May of 2003, he and his partner of 3 years began having unprotected anal sex.  His partner had tested HIV negative in 2002.  In July of 2004, his partner seroconverted.  Testing ruled out that the HIV came from a 3^rd person.

So Undetectable does not necessarily mean non transmissible.

We can all agree that ART and an undetectable viral load significantly reduce the risk of HIV being transmitted; but it does not eliminate the possibility.

Shedding, (which is a spike in virus) in the male genital tract happens even in men with consistently undetectable blood viral loads.  We still don’t know the genital tract viral load needed to transmit HIV.  So risk reduction is necessary.

Recommending safer sex practices for HIV infected is the best bet to prevent HIV transmission.

Gilbert Mallais

Treatment Information Facilitator/ Info-traitement Co-coordinator

Stürmer et al. Case report:  Is transmission of HIV-1 non-viraemic serodiscordant couples possible?  Antivir Ther 2008;13:729.

Over the hill with HIV!

By:Maria Lawrynowicz

Supervised by: Gilbert Mallais (Treatment Information Facilitator)

Thanks to the incredible advances in HAART treatment during the last 30 years, those living with HIV have a much higher life expectancy and improved quality of life. This has created a relatively new area of research interest that was unheard of just 20 years ago: aging with HIV. How does infection with HIV change the progression of the normal biological processes and associated pathologies that come with aging? Research into this domain is complex because it is difficult to track subjects over long periods of time. This study, however, not only looked at 1046 HIV+ patients in France who began treatment with anti-retroviral between 1997-1999, but also followed them for 10 years!! More studies should follow this lead because in the HIV+ community, it is no longer a question of worrying IF you make it “over-the-hill”, but WHAT you will do when you get there.

Ten-year diabetes incidence in 1046 HIV+ patients started on a combination antiretroviral treatment

AIDS volume 16(30) 28 January 2012 p303-314

Capeau, Jacqueline; Bouteloup, Vincent; Katlama, Christine;Bastard, Jean-Philippe; Guiyedi, Vincent; Salmon-Ceron, Dominique;Protopopescu, Camelia; Leport, Catherine; Raffi, Francois; Chêne, Geneviève

The late 90s saw an increase in diagnosis of type II diabetes in the HIV+ community. When tested, the patients lacked certain classic risk factors for diabetes such as, high blood pressure, family history, or hepatitis C infection; however, as testing continued several pattern emerged. Researchers found that the patients who received first generation protease inhibitors such as stavudine, indinavir, or didanosine had a higher chance (12.6% in women; 14.6% in men*) of developing diabetes. Interestingly enough, this trend was restricted to those with short term exposure to the drugs (likely because those who developed diabetes ceased treatment shortly after). Since then the drugs have been taken off the market in the West and are no longer used; however, in most cases, the diabetes persisted even after the treatment was halted.

More importantly, however, the study noted that age and fat content were found to be the best markers for diabetes, even better than the use of the first generation PIs. Due to the changes in fat distribution that occur with HIV, the HIV+ community must be vigilant of risk factors for diabetes and maintain a healthy lifestyle as it ages. HIV+ individuals should also have annual checkups to test fasting glycaemia and fat parameters, such as BMI and waist: hip ratio. Early detection of risk factors may allow patients to make simple lifestyle changes before having to revolutionize their lives with another complicated disease. As the saying goes, the grass is always greener on the other side, so keep your body in the best shape on the way there!

*[Keep in mind that this study was done in Europe. Had this study been done in North America, the results would likely be even more startling.]

INFO-TRAITEMENT CONFERENCES

Berlin Patient De-Mystified

- Maria Lawrynowicz
Supervised by: Gilbert Mallais

The legendary Berlin patient, Timothy Brown, is a constant reminder of the incredible scientific leaps taken in the last 30 years, but how many people actually know what it means to be “cured” of HIV and how this rare medical advance occurred? As always, it started with an idea put forth by Gero Hutter who was not aware how important his discovery would be to those millions of people with HIV and the many researchers and clinicians working on new methods of treatment who until then had not dared to think of the word “cure”. To help demystify this issue and illustrate what actually happened are the following drawings. Enjoy!

berlin patient

If you are interested in more information about the story behind the Berlin patient and his treatment, read the following article on: http://nymag.com/health/features/aids-cure-2011-6/

-Maria Lawrynowicz
Supervised by: Gilbert Mallais

The end of 2011 was abuzz with news of HIV vaccine FDA approval for testing in US/ Canada this year. This new vaccine is the first attempt at using a whole inactivated virus (of subtype B) as a preventative vaccine. Trials are to begin this month in phase I, while vaccine development itself began 10 years ago and preliminary research another ten years before that. Why does drug/ vaccine development take so long? What does phase I mean and assuming phase I is only at the start of the process, what is coming for these trials in the future?

Pre-clinical

This phase of the trial focuses on laboratory development of the active agent and testing if it works on the targets of interest. The SAV001vaccine is the first preventative vaccine that has been developed from an entire HIV virus. Why the first? Researchers were able to genetically alter the virus so it is unable to cause disease and then treated the inactivated virus with radiation and chemicals to further decrease activity. Prevention is difficult as HIV viruses continuously mutate, however, Dr. Chil-Yong Kang, the scientist behind this research, believes that using the whole virus may work based on success with other RNA viruses.

Clinical

The clinical trials begin with safety trials in animals to ensure that there is no toxicity.

Phase I

This vaccine is now in phase I of the drug development process. At this point, they are taking 40 healthy individuals to check its safety in humans specifically.

Phase II

If the vaccine passes phase I, it will then be tested on 600 HIV- patients from the “high risk group” to check the effectiveness of the vaccine in generating an immune response. This is the hardest phase for a drug to pass through, which means that although the active agent may seem to work well in vitro (in the lab), it may not effectively work on the target in vivo (in the human).

Phase III

This phase would take 6,000 HIV- volunteers which will either be vaccinated or not. These people will then be followed for the next 3 years to see how many have been infected with HIV.

Approval

Data collected in trails is then turned over to a governmental health agency, such as the FDA or Health Canada, and closely examined by their researchers. This phase may be accelerated when the therapy targets a disease that has no treatment or cure like HIV in the 1990s.

Post Market Surveillance

Phases IV/V occur once the drug is put on the market. In previous trials, rare adverse reactions to the drug were likely not yet found due to the small sample size. The drugs are constantly monitored while administered to patients and the results are sent back to the drug company.

All in all, drug and vaccine testing is a long tedious process that generally lasts about 12 years from start to finish and costs about 1 billion dollars. However, the hurdles are there for a reason: this process ensures that new treatments are safe, effective and can help a large portion of the HIV+ population. As the old adage says, good things come to those who wait…

Information on the specific HIV trial taken from: http://www.thestar.com/news/canada/article/1104653–canadian-developed-hiv-vaccine-approved-for-human-studies?bn=1

http://www.huffingtonpost.ca/2011/12/20/hiv-vaccine-canada-aids_n_1160527.html

http://www.theglobeandmail.com/life/health/new-health/health-news/canadian-developed-hiv-vaccine-approved-for-human-testing/article2277741/

http://www.ctv.ca/CTVNews/TopStories/20111220/canadian-hiv-vaccine-trials-111220/

-Maria Lawrynowicz
Supervised by: Gilbert Mallais

Everyone knows the feeling… lying in bed for hours, trying to get comfortable, and consistently re-calculating how much sleep you will get if you fall asleep now…or now… or now. Insomnia affects about 30% of the general population(depending on the study); however when combined with another illness, such as HIV, the number jumps to 60-70%. Whether it is caused by depression, anti-retroviral treatments, or cognitive health, insomnia can be debilitating and seriously compromise the quality of life of those HIV+.

Insomnia in HIV Infection: A Systematic Review of Prevalence, Correlates, and Management(2005)

By: Steven Reid and Justin Dwyer in Psychosomatic Medicine 67:260-269.

This article conducted a thorough literature analysis of 29 existing articles on insomnia and attempted to consolidate them into one major report. Despite the numerous papers written on the subject, there have been very little attempts to find consistent and effective treatment. The authors speculate that this is likely due to the variation in testing methods and experiments making it difficult to synthesize the data and find a comprehensive conclusion.

The analyzed studies were subdivided into two types: early and later studies. Early studies on insomnia and HIV examined the body’s function during sleep and noted changes to the different phases using polysomnography.  Although this is considered the best measure of sleep changes as it includes precise recordings of brain activity, breathing, heart rhythm, eye movement and muscle tone, it is also very expensive. This means that the number of people tested is usually small and patients are often only studied for 1-2 nights, which is not always representative of general sleep patterns. Despite being the most informative form of sleep study, personal accounts by the patient rarely agree with the data recorded. On the other hand, more recent studies are done by compiling questionnaires from personal experiences of those HIV+. Such surveys often include scales to rank the quality and quantity of sleep.

Due to the complex nature of HIV with changes to the immune system, drug therapies, and other related illnesses, researchers have been trying to draw relationships to insomnia, but this has generally been fruitless. To date there has not yet been a reliable relationship drawn between HIV and stage of infection based on immune cells. One study found a relationship to symptomatic late stage illness; however, this is likely due to an AIDS-defining illness and not the infection itself. It was found that cognitive impairment was one of the best predictors of insomnia in an HIV+ group. Anxiety, depression and other psychiatric disorders have well documented co-occurrence with insomnia and may also occur in those HIV+.

In addition, insomnia is a commonly listed side effect of antiretroviral therapy even though it is only occurs in 10%. A 2009 report outlined two cases where patients who started raltegravir, an HIV integrase inhibitor, experienced insomnia which went away shortly after discontinuation of the drug*. Often such rare side effects do not come out in the clinical trial and are not documented until the drug is put on the market. Efarvirenz is also believed to be an independent predictor of insomnia. In one study, 35% of those treated with drug developed insomnia during the month after treatment onset.

With all the information provided on insomnia and HIV, many questions remain unanswered and it is difficult to draw any concrete conclusions. Due to the small sample of most studies, many of the studies mentioned did not take into account other confounding variables (hidden variables that were not accounted for in the analysis and could change the results), such as amount of caffeine consumed or living conditions and did not control the data for other variables such as age, sex, race etc. These studies also lacked information on prevalence of insomnia in the group before becoming HIV+, thus we don’t know how many people had insomnia before even being diagnosed. Finally, the lack of uniformity in the definitions of ‘insomnia’ and experimental methods make it difficult to compare the information available.

Despite the clear lack of consensus in the research field, there are some small life changes which can be made before talking to your doctor about taking a sleep aid. The consumption of caffeine, alcohol, carbohydrates and refined sugars should be avoided after dinner time. Try sticking to green or white tea as a nightcap. Health permitting, do some light exercise everyday, but not in the few hours before bed! Avoid watching TV or working on your computer to fall asleep as the light will keep your brain buzzing. Set a time to put your electronics to bed then do some light reading for an hour allowing your brain to slowly turn off before you go to bed. Develop this schedule as a part of a routine. Our bodies are like machines, they work best when regularly turned on and off. So try to get up around the same time everyday and avoid sleeping in more than an hour- bummer, I know. If all else fails, talk to your doctor about going on a sleep medication and remember, do not take any herbal remedies without consulting with him/her as well!

It is surprising that despite the high level of insomnia in the HIV+ population and variable research in the field, there is little comparable information on treatments and causes. Insomnia, even in the general population, is most often left untreated. Hopefully researchers will begin testing efficacy of treatment methods in the HIV+ population in the near future. Fighting insomnia is an easy way to improve the quality of life of many HIV+ people so what are researchers waiting for…? Let’s call Mr. Sandman.

*Acute Onset Insomnia Associated with the Initiation of Raltegravir: A Report of Two Cases and Literature Review (2009)

By: Jacob Gray and Benjamin Young

Letter to the editor in AIDS patient care and STDs vol. 23 (9)

By: Maria Lawrynowicz
Supervised by: Gilbert Mallais

An end to HIV just screams prestige… awards… maybe even a Nobel prize… (not to mention, a cure for 27.3 million people currently known to be infected with HIV), so why aren’t more world leaders and researchers scrambling for this to become a reality? As so aptly stated by the author of R.I.P. HIV, Regan Hofmann, the real issue is not, “CAN we end AIDS?, but WILL we end AIDS?” With current research on neutralizing antibodies and CCR5 receptor inhibitors, scientists are getting closer to figuring out how to stop this disease, but how to move forward? According to Michel Sidibe, keynote speaker at the UNAIDS conference in Rome, “history will judge us not by our scientific breakthroughs, but how we apply them” and this is the point where we are today. It seems that the current issue boils down to two main points: lack of funding to start the end of HIV and lack of advocacy to get this funding. With so many philanthropic organization to donate to, HIV+ individuals need to let people know WHY to PICK their cause and HOW their money will make a difference.

R.I.P. HIV : Regan Hofmann

POZ magazine, Oct. 2011

http://www.poz.com/articles/RIP_HIV_AIDS_2666_21291.shtml

Hofmann divides the steps needed to defeat HIV into 7 points (as we all know, 7 is a lucky number):

1. POLITICAL WILL

·      In the US, Obama has stepped forward in HIV advocacy during his campaign by providing a framework for action known as the National HIV/AIDS strategy. This may seem like a win for HIV, however, with enormous budget cuts coming in the future, it is questionable whether this project will get funded and move forward.

·      In order to actually get anything done, North America (and the world) needs to focus on bi-partisan support for a cure to HIV/AIDS. Otherwise, each election will just result in the unraveling of the last president’s or prime minister’s plans.

2. MONEY

·      The current challenge facing funding is simple: the global recession. Despite projections that an investment today will save money in the future due to a decrease in money put into treatment of HIV or HIV related infections, most nations do not have liquid capital to invest.

·      Organizations that speak for those HIV+, must engage the private sector to find new investors. These organizations cannot keep relying on the Gates, Elton John, Ford, and MAC AIDS funds, which have raised millions of dollars in the past. HIV needs new supporters!

·      Finally, expanding access to anti-retrovirals around the world and thus, increasing the market for these goods, would give pharmaceutical companies a reason to drop prices. Why hasn’t this moved forward? Because big pharm has no assurance of getting the money back in the future.

3. ADVOCACY

·      Those fighting for HIV to get noticed need government support, but there are many ways to get this. HIV+ voters have the right to get angry when promises are not kept and remind politicians that they have the power to sway an election.

4. MEDIA

·      The support of one celebrity could make a enormous difference in the fight for funding. Just one tweet or post could reignite interest in social issues surrounding HIV.

·      Social media companies like youtube, google, facebook, twitter, tumblr, porn sites (for those open minded) have access to millions of viewers. Why not putting a message out for HIV?

5. THE CHURCH

·      Religious or faith based organizations have the potential to influence many people quickly due to their global outreach.

·      If the church allowed and encouraged believers to use condoms, increased their tolerance of GLBT, and spoke out against HIV stigma, those affiliated may be more likely to support this cause.

·      Finally, believers may be more likely to disclose their HIV+ status to a religious or spiritual leader, thus these people could be critical in determining the course of their treatment and helping them feel included in the community.

6. HUMAN RIGHTS

·      Empowering those HIV+ will increase adherence to medication and encourage people to get tested. These individuals need to know that they are protected by laws and by society so they know that getting a positive HIV test is not the end.

·      HIV discussion must not focus on “higher risk groups” as this kind of jargon encourages stigma and discrimination of many minority social groups.

·      All doctors and nurses MUST know about testing and treatment to successfully diagnose those HIV+ and get them on treatment ASAP. On the other hand, those who are not told of their status at a doctors office need to be aware of treatment, thus the media must make treatment options obvious and easy to find.

7. THE CURE

·      The cliché, “fight for a cure” rings true. The road to a cure is a fight… a fight to get noticed, a fight to get picked, a fight to get support, a fight to find funding. Ready, set…. Fight!

-Maria Lawrynowicz
Supervised by: Gilbert Mallais

Anti-retrovirals have had a huge impact on the quality of life of those living with HIV; however, individuals still react differently to treatment leading to a range of outcomes. Why? Some researchers believe that stress may play a large part in this difference. This study looked at meditation techniques and their effect on CD4+ t-cells in HIV+ adults. Because CD4+ cell decline is a marker for progression to AIDS, this is an excellent proxy for overall health in HIV patients.

Mindfulness meditation training effects on CD4+ T lymphocytes in HIV1 infected adults: a small randomized controlled trial

-J. David Creswell, Hector F. Myers, Steven W. Cole, Michael R. Irwin in 2009

http://www.sciencedirect.com/science/article/pii/S0889159108003085

The participants were HIV+ individuals who were diagnosed over 6 months ago and demonstrated minimal psychological stress symptoms. The sample excluded those who currently had AIDS, hepatitis or psychiatric treatment in the last 30 days, as well as, those who already did some kind of mind-body exercise. The chosen participants were put into two groups: the first had one 6 hour day of training in meditation, while the other was enrolled in an 8-week meditation program that included weekly training sessions, daily meditations guided by an audio recording and finally a meditation retreat. Because of the difficulty in standardizing meditation for research purposes, practitioners have developed a standardized ‘mindfulness-based stress reduction program’ (MBSR) to ensure that different studies can be compared.

When circulating CD4+ levels were compared before and after the meditation regimen, researchers noted a significant difference between the two groups. Those in the one day meditation program had a larger drop in CD4+ levels regardless of whether or not participants were on anti-retrovirals. Those participants in the 8 week program buffered their decrease in CD4+ cells in direct proportion to their adherence to the program. This means that the more often the patients went to meditation training, the better their CD4+ levels!

What could account for this difference? This could be due to the effect of meditation on t-cell redistribution in the body or turnover rate (i.e. when new cells are produced and old cells die). And even though this study saw no significant changes in HIV RNA levels, other studies show that stress increases viral replication, so this cannot be excluded as a possibility. One problem with this study is that the researchers did not compare the ‘mindfulness based stress reduction’ program to other stress reduction techniques so it may be possible to get these benefits by other measures, we just don’t know yet.

So why not try it? Meditation has many health benefits, requires limited training at low cost, and has been shown to make you happier! Increasing CD4+ levels while reaching enlightenment… not a bad deal.

-Maria Lawrynowicz
Supervised by: Gilbert Mallais

Remember the CATIE article on HIV and aging? It said that more effective anti-retroviral therapy since the 1990s has increased the incidence of dementia in HIV patients and advised HIV+ individuals to seek medical advice when they have memory or focus issues. My question is who DOESN’T have memory and focus issues? How do you draw the line between what is normal and not? This article seems to offer some insight into what we do and do not know (mostly the later), as well as, what we should try to find out…

HIV Infection and Aging Independently Affect Brain Function as Measured by Functional Magnetic Resonance Imaging

Beau M. Ances,
Florin Vaida,
Melinda J. Yeh,
Christine L. Liang,
Richard B. Buxton,
Scott Letendre,
J. Allen McCutchan,
Ronald J. Ellis

available at: http://jid.oxfordjournals.org/content/201/3/336.full

Study presented at Conference on Retroviruses and Opportunistic Infections, Montreal; 8-11 February 2009

Compliant HIV+ patients could be considered a doctor’s dream… they are capable of following complex medication schedules, visit their doctors on a regular basis and lead a relatively healthy lifestyle, while staying mindful of their diet, exercise and so on. Such individuals are no strangers to minor body ailments that may come with a seropositive status and are accustomed to treating these as they come, however, it is much more difficult to perceive the highly camouflaged symptoms of cognitive changes from neuronal degradation with aging and/or HIV. Even the most vigilant people can fail to notice vague things, like forgetfulness or decreased concentration, often passing these off as “one of those days”.

Top 3 points from this article:

1. A group of HIV+/- subjects were examined with a fMRI (functional magnetic resonance imaging is known as “functional” because it measures changes in blood flow while your brain is working) to measure their cerebral blood flow and dissolved O2. The study found that cerebral blood flow of HIV+ subjects was similar to HIV- subjects who were 21 years older, while blood oxygen dependent signals were like those of HIV- individuals 15 years older.

2. What is causing this extra strain on the brain? Scientists believe that the increased metabolic stress due to normal aging compounded with metabolic stress from persistent inflammation that comes with any infection (even in HIV when you have an undetectable viral load), or immune dysfunctions, like reduced t-cell growth/ maturation or increased cytokine release (chemicals released by your immune cells to fight off infections),

3. What is the good news? There is no synergistic effect of aging and HIV infections i.e. they both function independently! What does this mean? Independent risk factors are discrete things that predispose people to a particular condition, in this case, HIV associated neurocognitive disorder. This means that BOTH being HIV+ and aging does not make it any more or less probable that your brain will have a neurocognitive disorder. With this information, future studies should be directed at determining causality (why does blood flow change?) so that researchers can work to find a therapy that could mediate the effects seen in this study. This study opens the door to potentially important changes in HAART in the coming years….

If you are in Montreal, a student at McGill university, and 18+ you can participate in a trial for a rapid HIV test. Call Student Health Services at 514-398-6017 to make an appointment with a nurse.
Participants will be compensated for their time.