Friday, December 16, 2016

World AIDS 2016

World AIDS  2016
By Dr. Ali Fourkan
On this World AIDS, I want to remind you of our history.  We are a movement of people who changed the world.  Together we built a unique healthcare infrastructure because nobody would take care of our friends.  We held the hands, comforted the families, and buried our friends and lovers with dignity, even when many funeral homes refused to transport them.  When local social service agencies turned us away, we built a network of nonprofits across the country to fight a disease that nobody cares about.  AIDS activism changed the way drugs were approved and laws were enacted.  Activism captured our nation’s attention about a disease that most people did not want to discuss.  Working with our global friends, we fought to bring treatment to the world, even when everyone said it’s not possible.  All too often we heard the words impossible, you can’t do it, yet we did. We find ourselves at another great moment of change.  It can seem scary or overwhelming.  Our movement needs strong leaders who understood how to push the system.  Leaders who value inside and outside strategies.  Leadership cannot be limited to the few, it needs to be at all levels of our work, doing a variety of tasks and filling a diversity of positions.
The HIV movement depends on government funds to provide medication, healthcare, social services, housing and support to the 1.2 million Americans living with HIV and prevention services to reduce the number of new infections that are stubbornly stuck at around 40,000 annual new HIV-infected individuals.  To provide these needed life-saving services, we must work with President-elect Trump and Congress. Our movement survived the loss of friends and family.  We learned to stand up when others turned their backs against us.  We built systems of care and prevention services where none previously existed.  During the darkest days of the epidemic, it was our hope and passion that got us through the difficult times.  Because I know our past, I am not afraid for our future.  There will be difficult moments, but we are a strong vital community that stands on the shoulders of heroes.  NMACthanks everyone who has dedicated their life to fighting this epidemic. 
HIV vaccine steps closer with new insights into broadly neutralizing antibodies
Scientists reveal new insights into the human body's ability to produce broadly neutralizing antibodies to HIV that promise to open new avenues for vaccine development.
Scientists say their new information on broadly neutralizing antibodies may bring us closer to an HIV vaccine.
Once the HIV enters the body, the immune system starts to produce antibodies to fight the pathogen. Generally, the antibodies produced are specific to the particular strain of HIV.
However, research reveals that around 1 percent of HIV-infected people produce broadly neutralizing antibodies that attack different strains of HIV that circulate worldwide.
Broadly neutralizing antibodies bind to structures or "spikes" on the surface of the virus that arise from the virus itself and vary little among different strains.
Much of the search for an HIV vaccine focuses on better understanding how broadly neutralizing antibodies form and attach to the spikes.
In a paper published in the journal Nature Medicine, researchers from the University of Zurich and University Hospital Zurich (UZH) in Switzerland describe how they found disease-specific, host-specific, and virus-specific factors that appear to influence the body's ability to make broadly neutralizing antibodies against HIV.
For the study, the team examined around 4,500 people infected with HIV - all participants of the Swiss HIV Cohort Study and the Zurich Primary HIV Infection Study. They found 239 of the participants formed broadly neutralizing antibodies.
Disease, virus, and host factors
The researchers found three important disease-specific features that appear key for the production of broadly neutralizing antibodies: the number of viruses present in the body, the diversity of virus types, and how long the HIV infection had gone untreated.
Huldrych Günthard, professor of clinical infectious diseases at UZH and one of the study's corresponding authors, says their study is the first to identify these three disease-specific features.
He says they also found that the features influence the production of broadly neutralizing antibodies independently of each other, and explains:
"So we don't necessarily have to consider all three parameters in designing an HIV vaccine. This is especially important with regard to the length of vaccine administration - it wouldn't be possible to imitate a longer untreated HIV infection with a vaccine."
The important host-specific feature concerns ethnicity. The team found black participants infected with HIV appear to make broadly neutralizing antibodies more frequently than white people - regardless of other factors the study analyzed.
Co-author Alexandra Trkola, a professor of medical virology at UZH, suggests this factor needs further investigation in order to better understand how ethnic origin affects production of broadly neutralizing HIV antibodies. Factors likely to play a role could be genetics, geographics, and socioeconomics.
Finally, the team found that different virus subtypes appear to affect the binding site the antibodies attach to. Subtype B viruses are more likely to spur the body to make HIV antibodies that bind to CD4 binding sites - through which the virus binds to host immune cells.
In contrast, non-subtype B viruses appear to encourage production of antibodies that bind to a sugar element of the virus spikes (V2 glycan).
Smoking more hazardous for HIV patients than the virus itself
Cigarette smokers who are HIV positive appear to have a higher chance of dying from smoking-related complications than from HIV, according to research published in the Journal of Infectious Diseases.
Numerous health problems are associated with smoking. Smokers have a high chance of developing heart disease, cancer, serious lung diseases, and other infections, such as pneumonia.
Previous research has suggested that each cigarette shortens a person's lifespan by 11 minutes, and that smoking from the age of 17-71 years will decrease life expectancy by an average of 6 ½ years.
HIV is a serious health condition. Untreated, it can lead to AIDS, which is fatal. Once a person has HIV, it will never leave their body. HIV affects the body's immune system, so that it can no longer fight off infections.
In 2014, around 44,073 people were diagnosed with HIV in the United States.
More than 40 percent of people with HIV are smokers, compared with 15 percent for the general population in the U.S. The number of people with HIV who smoke in the U.S. is estimated to be around 247,586. Another 20 percent of people with HIV are former smokers.
HIV patients more prone to the ill effects of tobacco
Current HIV treatments offer effective protection against the virus, so that people with the virus are living for longer, but people who have HIV remain especially susceptible to the risks of smoking.
Compared with other smokers, they are more likely to experience:
Pneumocystis pneumonia, a dangerous lung infection
Chronic obstructive pulmonary disease (COPD)
Heart disease and stroke
Lung cancer and other types of cancer.
Researchers from Massachusetts General Hospital and Harvard Medical School in Boston, MA, projected the effects of smoking and HIV on life expectancy.
Patients may lose up to 6.7 years
Using a computer simulation of HIV disease and treatment, the authors calculated the life expectancy of people with HIV, based on whether or not they smoked.
Fast facts about HIV and AIDS
Over 1.2 million people live with HIV in the U.S.
From 2005 to 2014, annual diagnoses fell by 19 percent
81 percent of HIV patients are men.
In the U.S., it is common for people with HIV to abandon their drug treatment and care regimen. The current study factored this into the projections, making the results particularly relevant for U.S. patients and health providers.
Findings showed that in people with HIV who follow their treatment correctly, smoking decreases their life expectancy by about twice as much as HIV does.
For men with HIV, the loss of life expectancy for HIV and for smoking was similar, whether or not they followed their treatment regime.
Male smokers who started HIV treatment at the age of 40 years stood to lose 6.7 years of life expectancy, and women, 6.3 years, compared with those who never smoked. Men who quit smoking and started treatment at 40 years would regain 5.7 years of life, and women, 4.6 years.
The authors conclude that people with HIV who follow their treatment but also smoke are far more likely to die of a smoking-related disease than from HIV itself.
They call for smoking cessation to be prioritized for patients with HIV. Helping them to quit smoking could significantly improve their life expectancy.
Co-author Dr. Krishna P. Reddy points out that even if a person smokes until the age of 60 years and then quits, they will have a significantly longer life expectancy than someone who does not quit.
"Now that HIV-specific medicines are so effective against the virus itself, we also need to add other interventions that could improve and extend the lives of people with HIV."
The team calls for smoking cessation to play a key role in care programs for people living with HIV. They recommend further research into the best way to help people with HIV to quit.
They also suggest investigating the health and economic benefits of quitting smoking among people living with HIV.
Dr. Keri N. Althoff, of the Johns Hopkins Bloomberg School of Public Health, comments in an accompanying editorial: "This study makes clear that we must prioritize smoking cessation among adults with HIV if we want them to have an increase in the quantity (and likely quality) of life."
HIV: New, powerful technique finds dormant virus hiding in rare cells
Usually, antiretroviral drugs control HIV levels in infected people and prevent them developing full-blown AIDS. However, some viruses stay hidden for years and flare up if patients cease treatment or if treatment fails. Now, scientists have discovered a powerful way to wake up dormant HIV and locate the rare cells that hide it.
Viruses cause disease by entering host cells and taking over their cell machinery to make copies of themselves.
HIV targets immune system cells and weakens people's immunity to infections and ability to fight some types of cancer.
According to the World Health Organization (WHO), there are approximately 37 million people worldwide living with HIV, and around 2 million were newly infected in 2015.
If not treated, HIV infection progresses to the most advanced stage - Acquired Immunodeficiency Syndrome (AIDS). This can take 2-15 years, depending on the individual.
There is no cure for HIV infection. However, effective antiretroviral (ART) therapy can control the virus and help prevent transmission.
HIV reservoirs are cells and tissues where HIV persists, despite ART. The virus mostly lives and copies itself in CD4+ T lymphocytes, a type of white blood cell.
While ART is generally successful at controlling the viral load in people with HIV and stopping them progressing to AIDS, the HIV can stay dormant for years and wakes up when patients stop their therapy.
Waking up dormant HIV
In the journal Cell Host & Microbe, researchers from Canada and the United States report how they discovered a way to reactivate dormant HIV and find the very rare cells that are hiding it.
Fast facts about HIV/AIDS
To date, the total global death toll to HIV is 35 million lives
Estimates suggest only 54 percent of people with HIV know they have it
During 2000-2015, new HIV infections fell by 35 percent.
Senior author Dr. Daniel Kaufmann, associate clinical professor in the department of medicine at the University of Montreal, says that in order to develop treatments that target residual infected cells, you have to find precisely where they are in CD4+ T lymphocyte populations, which are highly variable. He explains:
"Our research has uncovered these HIV hiding places. We were able to identify and quantify the cells containing hidden virus and then test drugs to wake up HIV."
With his team, Dr. Kaufmann, who is also a researcher and infectious disease specialist at the University of Montreal Hospital Centre (CHUM), developed an innovative way to find the residual infected cells.
Their method can be likened to "taking a photograph" of each individual cell harboring dormant HIV. This represents a significant breakthrough, as it is about 1,000 times more accurate than current technologies.
The team analyzed blood from 30 patients with HIV, sampled before and after they started on ART. They were able to detect the virus in CD4+ T lymphocytes in almost all of them.
The idea is that once you find where dormant HIV is hiding, then you find drugs to wake it up and make it visible so the immune system or ART can kill it.
In the next phase of the study, they tested two drugs to wake up the dormant virus - so-called latency reversal drugs. The drugs, bryostatin and a derivative of ingenol, were developed to fight cancer but may also be used to fight HIV.
Different patients may need different treatments
The researchers discovered that the two drugs woke up two different populations of CD4+ T lymphocytes. They note in particular that the ingenol derivative activated a population called central memory cells, which can live for years in patients.
Dr. Kaufmann says while their studies were done in the lab, "a clinical trial would involve using such drugs to wake up the virus while the patient continues taking ART to ensure that the reactivated virus cannot infect other cells."
At first the team assumed HIV hid in similar places in different patients. However, they found this not to be the case - it varied a lot from patient to patient. Dr. Kaufmann explains:
"We may have to adjust the treatment for individual patients, depending on the specific HIV hiding places in each case. To minimize the virus pools, we will have to assess patients and tailor the 'shock and kill' therapies to their profiles."
The team's next step is to evaluate the effectiveness of new drugs to wake up similar virus reservoirs in monkeys. If the drugs are well tolerated, then clinical trials in humans can go ahead in a few years.
HIV update - 7th December 2016
NHS England will make PrEP available next year
NHS England and Public Health England have given an outline of a large study of the best way for the NHS to implement pre-exposure prophylaxis (PrEP), which is due to start in the middle of next year. This follows the Court of Appeal’s ruling last month that NHS England, alongside local authorities, has the power, but not the obligation, to fund PrEP and should plan how to provide it.
While many activists would have preferred the NHS to announce an immediate roll-out of PrEP to all who need it, there was also the risk that the NHS would have decided that PrEP was too expensive to provide at the moment.
The study may allow a significant number of people to get access to PrEP – around 10,000 people may take part over a three-year period. A large trial may be possible because NHS England and Public Health England are trying to drive the price of PrEP drugs down by pitting generic companies and Gilead (the pharmaceutical company that produces Truvada) against each other in a bidding war.  
We know that the study will not be directed exclusively at gay men or any other population, but very few details of the trial have been settled. It is not clear whether the trial will be run at sexual health clinics across England, or only in a few selected locations.
Deborah Gold of the National AIDS Trust, which took NHS England to court, said that the trial would not be happening without the legal challenge, a series of parliamentary questions and strong community pressure for PrEP. “We are absolutely delighted that following our wins in Court, NHS England, working with Public Health England and local government will be now making PrEP available on a large scale, and quickly, to those who need it,” she said.
Greg Owen of iwantPrEPnow welcomed the announcement but said that the plans are not a permanent solution to wider PrEP provision. He called on NHS England to ensure that the limited availability of PrEP is targeted so it does not worsen existing health inequalities.

Real-world data on hepatitis C treatment for people living with HIV
More than 90% of HIV-positive people treated with direct-acting antivirals for hepatitis C were cured of hepatitis C and few stopped treatment due to side-effects, showing that real-world clinical practice can produce results as good as those seen in formal clinical trials, according to Spanish data.
People who take part in clinical trials are not always typical of other patients, and they also get extra monitoring and support. For that reason, there is a possibility that results in clinical trials will be better than in routine medical care.
But these data provide reassurance on that point. They show that people living with HIV can have excellent results with modern hepatitis C drugs.
In Madrid, doctors are obliged to record details of all patients who have HIV and hepatitis C co-infection. The analysis therefore includes all 2300 people in Madrid who started hepatitis C treatment over an 18-month period. Most were men and their average age was 50. Importantly, just under half had cirrhosis, indicating significant damage to the liver.
The drugs most commonly used were:
Sofosbuvir and ledipasvir (Harvoni combined tablet)
Sofosbuvir (Sovaldi) and daclatasvir (Daklinza)
the paritaprevir-based '3D' regimen (Viekirax + Exviera).
Overall, 92% of people had a continued undetectable hepatitis C viral load 12 weeks after completing treatment (i.e. sustained virological response or SVR12). This outcome suggests that the person has been cured of hepatitis C. Cure rates were similar between people with genotypes 1a, 1b, 3 and 4.
People with compensated cirrhosis (the earlier stage of cirrhosis, during which the liver is damaged but still able to perform most of its functions) had cure rates almost as good as those without cirrhosis. However, in people with decompensated cirrhosis (the later stage), cure rates were lower at 81%.
Less than 1% of people stopped treatment because of side-effects.
The results confirm that treatment outcomes are similar for people with co-infection and for people with hepatitis C alone.
For more information on this topic, read NAM’s booklet ‘HIV & hepatitis’.
Top 10 HIV Clinical Developments of 2016
In typical years, a noteworthy development in the world of HIV would be the result of a landmark clinical trial or perhaps a gem of a lab study with a novel finding. But, 2016 was not typical. What made the most difference for people living with HIV and their health care providers this past year was less a paper published or presented than major shifts in our thinking about how best to prevent and manage HIV infection.
This was the year of the "shake-up" and the eschewing of the good-enough status quo. HIV-positive patients and their providers, traditionally cautious in their approach to treatment, have recently become willing to embrace change, including to antiretroviral regimens. "Switch and simplification" have replaced "stay the course" as a guiding HIV therapeutics mantra. New drugs and formulations offer treatment options that are markedly easier and safer than the medications on hand just a year or two ago. Even the dogma regarding what constitutes highly active antiretroviral therapy (ART) is being questioned by daring ART minimalists for whom fewer drugs mean lower risks and costs. At the same time, the movement that advocated successfully for earlier administration of HIV therapy is now pushing for provision of medications the same day a patient presents for testing. For all this radicalism, there were also throwbacks to retro ideas, such as using antibodies to fight HIV -- an approach that was tried but failed early in the epidemic.
Overshadowing this evolution of thought were the results of the presidential election and the delivery of control of both the House and Senate, as well as a few governorships, to the Republican Party. Perhaps no other development will have as much impact (think: comet, dinosaurs) on the future of people living with HIV as the 2016 elections -- and that is where we start.
Source of Table of Contents
David Alain Wohl, M.D., is a professor in the Division of Infectious Diseases at the University of North Carolina at Chapel Hill, director of the North Carolina AIDS Training and Education Center and site leader of the University of North Carolina Chapel Hill AIDS Clinical Research Site.
The writer Teacher & Columnist
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Dr.fourkanali@gmail.com

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