Efficacy of a Two-Drug ART Regimen for Initial HIV Therapy


In a pilot single-arm study, the two-drug regimen dolutegravir + lamivudine achieved viral suppression in 90% of patients at 24 weeks.

Increasing data support use of certain two-drug antiretroviral (ART) regimens for maintenance therapy for select HIV-infected patients suppressed on a standard ART regimen (NEJM JW Infect Dis Jan 2018). Experience with two-drug ART regimens for initial HIV therapy has been less favorable. In this pilot study, the two-drug regimen dolutegravir + lamivudine (3TC) was evaluated in treatment-naive HIV-infected patients without active hepatitis B infection who had HIV RNA levels ≥1000 and <500,000 copies/mL. The planned primary endpoint was the proportion with HIV RNA <50 copies/mL at week 24.

The study enrolled 120 persons at 26 sites in the U.S. (median HIV RNA, 4.6 log10 copies/mL; median CD4 count, 387 cells/mm3; 87% male; 72% nonwhite). At 24 weeks, 108 (90%) of the participants had HIV levels <50 copies/mL; results were similar for those with HIV RNA >100,000 or ≤ 100,000 copies/mL. Three participants met criteria for virologic failure; all had undetectable dolutegravir levels at ≥1 time points and one had M184V and R263R/K integrase mutations identified at time of failure. The regimen was well tolerated, with no treatment discontinuations due to adverse effects. The authors conclude that these results support further evaluation in select treatment-naive patients planned in the currently enrolling phase 3 studies.

Comment

Dolutegravir/3TC is a regimen of interest due to the potency and high barrier to resistance of dolutegravir and the potency, tolerability, and low cost of generic 3TC. Although these results are encouraging from the efficacy standpoint, the development of resistance to dolutegravir is worrisome and has not been generally observed with dolutegravir use as part of initial three-drug therapy. Results of the phase 3 GEMINI-1 and 2 trials comparing dolutegravir/3TC to a standard three-drug regimen for initial treatment (https://clinicaltrials.gov/ct2/show/results/NCT02831764), anticipated in 2018, will provide more definitive data on the potential of this two-drug regimen.

PrEP Isn’t Just for Men Who Have Sex With Men—Should You Be on It?


Here’s what you need to know about the drug that prevents HIV.
Prep-Medication

You’ve probably heard of PrEP, maybe from a friend, an advertisement, or in health class. Regardless of how it came up, it was most likely referred to as something for men—specifically men who have sex with other men and want to avoid contracting HIV.

PrEP is a medication that can drastically lower someone’s risk of getting HIV. An estimated 120,000 people in the United States were taking it for that purpose at the start of 2017, according to a report from Gilead Sciences, PrEP’s manufacturer. But PrEP can help anyone at risk for HIV infection reduce that risk, no matter their gender or sexual orientation. Here’s what you need to know about HIV, how PrEP protects against it, and whether you should consider taking this drug.

First, here’s a primer on HIV and how it’s transmitted, which is essential in understanding why PrEP is so effective.

HIV, or human immunodeficiency virus, is spread through certain bodily fluids (blood, semen, pre-seminal fluid, vaginal and rectal fluids, and breast milk) from a person who has HIV, according to the CDC. It attacks the immune system by killing off a person’s T cells, aka CD4 cells, which help the body battle infection. If you don’t have enough of these cells, you’re more vulnerable to illnesses.

According to the most recent CDC data available, 1.1 million people in the United States had HIV in 2015. After peaking around 150,000 per year in the mid-1980s, the number of new HIV diagnoses gradually decreased and sat at 39,782 in 2016.

Men who have sex with men are at the highest risk of contracting HIV because receptive anal sex has the highest potential transmission rate of all types of exposure except blood transfusions. According to the CDC, the risk of contracting HIV through unprotected receptive anal sex with a person who has it is 138 per 10,000 exposures. This is because the delicate lining of the rectum is so thin that it can allow HIV to enter the body more easily.

For comparison’s sake, the chance of getting HIV from a blood transfusion from a person who has the virus is 9,250 per 10,000 exposures. The odds drop to 63 per 10,000 exposures for needle sharing during intravenous drug use, 11 per 10,000 exposures for insertive anal sex, 8 per 10,000 exposures for receptive penile-vaginal intercourse, and 4 per 10,000 exposures for insertive penile-vaginal intercourse. The risk from receiving or giving oral sex is “so low that it is not possible to put a precise number on it,” and the risk from things like biting and sharing sex toys is “negligible.”

Certain factors, like using condoms when possible and not letting a person ejaculate inside of you, can lower your risk. Others, like having other sexually transmitted infections, may raise it.

Contrary to a popular and damaging myth, HIV is not a death sentence.

A person infected with HIV who gets treatment early can live a happy, active life for nearly as long as a person without it, according to the CDC. This is because HIV medications can do an incredible job of preventing the disease from progressing into AIDS.

A person is diagnosed with AIDS, or acquired immunodeficiency syndrome, when HIV has attacked their system to the point where their CD4 count drops below 200 per cubic millimeter of blood, according to the CDC. This allows life-threatening “opportunistic infections” like pneumonia, tuberculosis, and various cancers, to wreak havoc on a person’s health.

HIV medications known as antiretroviral therapy (ART) can slow the progression of the disease and lower the chances of transmitting it to others. ART for people with HIV typically includes three medications from two different drug classes, according to the U.S. Department of Health and Human Services.

PrEP is the latest tool in the fight against HIV, and it works to prevent the infection from taking hold in the first place.

PrEP is a daily pill for HIV-negative people that, when taken consistently, can reduce the risk of HIV infection through sex by over 90 percent, according to the CDC. It can also lower the risk of HIV contraction in someone who injects drugs by over 70 percent when taken daily, according to the CDC.

PrEP comes as a pill under the brand name Truvada, which is actually a mix of the HIV medicines tenofovir and emtricitabine, and was first approved for use in the U.S. to prevent HIV in July 2012.

“These drugs were chosen because they have limited side effects, have few problems with drug resistance, and remain in the body for a relatively long time,” Mehri McKellar, M.D., an associate professor at Duke University’s Division of Infectious Diseases, tells SELF.

PrEP basically preloads your body with medicine, family doctor Adam Lake, M.D., an American Academy of HIV Medicine specialist working for Lancaster General Health in Lancaster, Pennsylvania, tells SELF. If exposure does occur, PrEP blocks pathways the HIV virus uses to infect your body. This prevents HIV from establishing itself so you can remain HIV negative.

It’s worth noting that PrEP is different from post-exposure prophylaxis (PEP), which can be taken within 72 hours after possible HIV exposure (like a sexual assault) and continued for the prescribed 28 days. When taken as directed, this antiretroviral treatment can stop the infection from taking hold in someone’s system. PrEP isn’t 100 percent effective in preventing HIV transmission, but the sooner it’s started, the better.

The problem is that some at-risk populations aren’t benefiting from PrEP as much as they could be.

Rates of new HIV diagnoses are highest for black and Hispanic/Latino gay and bisexual men, according to 2016 data from the CDC. Unfortunately, despite the fact that the majority of those living with HIV are people of color, 73 percent of people who filled PrEP prescriptions between January 2012 and September 2016 were white, according to Gilead Science’s 2017 report. “We need to make sure that African-Americans and Latinx are aware of PrEP and have access to this medication,” Dr. McKellar says.

And while the risk of HIV is highest among men who have sex with men, that doesn’t mean that other individuals (particularly those with other risk factors) can’t benefit from PrEP. That’s why Dr. Lake wishes more sex workers, intravenous drug users, and sexually active trans women knew about and had better access to PrEP, since their lifestyles put them at higher than average risk. So does being a cisgender woman or gender nonconforming person who’s had unprotected vaginal or anal sex with two or more partners in the last year, or who has a partner who has HIV or HIV risk factors.

If you’re concerned or meet certain risk factors, Dr. Lake suggests asking your doctor about PrEP. This doesn’t mean you definitely need to go on PrEP if you meet the qualifications. But it’s worth discussing with your doctor to see if your personal situation makes it a good choice for you, especially because you wouldn’t need to take it forever—only during periods of your life in which you’re at risk.

Of course, cost and side effects are both important considerations.

While PrEP’s cost varies depending on insurance, it can be prohibitively expensive, which is a hindrance to many people who need it. Without insurance, PrEP can cost up to $13,000 a year, according to the PrEP Facts, an awareness-raising project from the San Francisco AIDS Foundation and San Francisco Department of Health, among other groups.

There are, however, programs aimed at granting affordable access to those without insurance or those who need assistance paying their co-pays. If you have non-government insurance, you may be eligible for the Gilead Advancing Access program, which can offer up to $3,600 per year to help with co-pays based on your situation (you can learn more about the program’s terms here for the program’s full terms). If you don’t have insurance, are eligible for Medicaid, or your insurance denies your claim, the PrEP medication assistance program may help you get the drug for free. The CDC created a handy spreadsheet about paying for PrEP that you can check out, too. If all of this is confusing, you can ask your doctor if they have any information on how to lower the cost of PrEP or find an HIV-focused health center near you for more information.

Like any other medication, PrEP can have side effects. The most common ones are headache, abdominal pain, and weight loss, though in rarer cases it can cause kidney issues, liver and bone problems, and too much lactic acid buildup in your blood, which can be life-threatening. Make sure to discuss these risks thoroughly with your doctor before starting PrEP so you’re aware of any symptoms that are waving red flags.

Finally, the medication can only do its job well if you take it every day. It gets less effective if you don’t take it daily—commitment is key.

Even if PrEP isn’t right for you, it’s imperative that you know your HIV status, which is only possible through regular testing.

Regardless of your gender, orientation, or lifestyle, the CDC recommends that everyone between the ages of 13 and 64 get tested for HIV at least once. If you have certain risk factors like being sexually active, having been diagnosed with any sexually transmitted infections, and having had sex recently with someone whose history you don’t know, you should get tested at least once a year. The CDC also recommends that gay or bisexual men consider getting tested every three to six months.

There are various kinds of HIV tests available, including blood tests and oral swab tests. Some tests can give you results in 20 to 30 minutes, while other lab-based tests can take up to several days. Most forms of HIV testing can detect the virus in your body about 18 to 90 days after exposure, according to the CDC (so if you tested negative a few days after having unprotected sex, you should ask your doctor when to come in for another test). In general, tests that use blood from a vein can detect HIV sooner after infection than finger prick tests or oral swab tests.

The only way to know your and your partner’s HIV status is to get tested, and this is an especially necessary step to take if you’re considering not using condoms. Talking about HIV can feel scary, but let your partner know that you want to feel comfortable with them and getting tested will help quell your fears.

As a bonus, going in to get tested is the perfect time to ask your doctor whether you might be a good candidate for PrEP. If you think you’re at risk for contracting HIV—or are just curious about how well you’re protecting yourself, get tested and ask your doctor about what resources can help you have a healthier, safer sex life.

HIV’s Jump From Apes to Humans May Have Been Aided by an Unfortunate Deficiency


Nobody knows quite when it happened. But some time in our not too distant past, a chimpanzee version of a pathogen known as simian immunodeficiency virus (SIVcpz) jumped species to infect humans.

Mutations in SIVcpz would turn it into the insidious human immunodeficiency virus (HIV-1) responsible for the global AIDS epidemic. New research suggests a common group of proteins should have protected us from infection, raising the question – how did it happen?

An international team led by researchers from the Heinrich-Heine-Universität Düsseldorf have investigated how a group of proteins called cellular cytidine deaminases (APOBEC3s or A3s in short) can offer humans protection from the virus that attacks apes.

Specifically, the scientists focussed on variants of a gene responsible for the cytidine deaminase APOBEC3H (A3H) and its role in the replication and possible transmission of the chimpanzee-specific virus.

The story of the rise of the HIV epidemic is murky up to the point when the first AIDS patients were reported in the US in the early 1980s.

While researchers can show a relationship with the simian version of the immunodeficiency virus, we can only speculate on how and when the virus leapt from apes to humans.

The transmission was more than likely passed through infected blood from meat, probably captured for food, and occurred far enough back in recent history for the virus to have had time to evolve into its current form.

Exactly why it happened at that moment – whether due to mutations or an unfortunate series of events – is still something of a mystery. But this new study could help shed some light on the question.

It’s known that the A3H cytidine deaminase proteins restrict the replication of the family of viruses both HIV and SIV belong to.

Usually these viruses can retaliate with a secret weapon of their own – a protective virulence factor called vif. But it doesn’t work as well against all versions of these anti-viral proteins.

What hasn’t been investigated until now is whether the human form of these proteins could have stopped the ape-infecting virus dead in its tracks in people.

To determine the extent of the proteins’ potential virus-busting powers, the researchers infected cultures of human kidney cells with easily-traced simian viruses from various sources. They also dosed the cells with genes to make either human or chimpanzee anti-viral proteins.

One particular human A3 protein called A3H haplotype II stood out from the crowd. It was particularly resistant to the virus’s vif, allowing it to sidestep the defence and rip into the SIV’s genes.

Turning to data from the Great Ape Genome Project, it was found that the chimpanzee version of A3H was less diverse than the human one.

What’s more, further experiments showed vif from chimpanzee and gorilla SIV could still interfere with chimpanzee A3H.

Taken together, it makes a compelling case for the hypothesis that humans evolved a solid defence against SIV.

That might go some way in explaining why in spite of living side by side with populations of great apes for so long, the leap of SIV to HIV was a significant recent event. But why did it happen at all?

Diversity can swing both ways. While humans clearly have evolved some remarkable versions of APOBEC that offer protection from SIVcpz, it’s likely that some individuals could lack that protection, or possess a weak or unstable version.

Scientists will be adding this puzzle piece to the collection, as future research continues to look at the relationship between cytidine deaminase and HIV – and it could help finally provide some answers.

CRISPR Gene Editing Has Been Used to Cure Mice of Sickle Cell Disease


IN BRIEF
  • The results are promising and could lead to a treatment for this disease that afflicts about 100,000 Americans.
  • While human tests are still a ways off, CRISPR could one day be used to effectively treat a number of ailments, from high cholesterol to HIV.

CORRECTING A MUTATION

Gene editing shows promise as a new treatment for sickle cell disease, according to a study published in the online journal Science Translational Medicine.

Experts from the University of California, Berkeley, UCSF Benioff Children’s Hospital Oakland Research Institute (CHORI), and the University of Utah School of Medicine have found success in correcting the blood cell mutation in tests of the blood of both mice and human sickle cell patients using CRISPR-Cas9, a genome “scissor” that can cut out and edit a DNA sequence.

After CRISPR was used to correct the mutated hematopoietic stem cells — precursor cells that mature into the hook-shaped hemoglobin characteristic of sickle cell disease, the corrected blood stem cells produced healthy hemoglobin. Following reintroduction into the mice, the genetically engineered stem cells remained in circulation for at least four months — a significant indication that any potential therapy would be lasting.

 The tests of blood from afflicted humans showed that the proportion of corrected stem cells was high enough to produce substantial benefit for the patients, so the researchers are hoping to one day be able to reinfuse the human patients with the edited strain of cells as it could alleviate symptoms of sickle cell disease, including anemia and pain caused by vessel blockages.

While the results are promising and could lead to a treatment for this disease that afflicts about 100,000 Americans, the researchers emphasize that future testing on mice and safety analyses would need to be conducted before human trials could begin.

A CRISPR’D FUTURE

“Sickle cell disease is just one of many blood disorders caused by a single mutation in the genome,” said Jacob Corn, senior author on the study. “It’s very possible that other researchers and clinicians could use this type of gene editing to explore ways to cure a large number of diseases.”

Indeed, developments in gene-editing  technology within such fields as medicine, agriculture, and biology are taking us further into what some are calling “the age of CRISPR.”

It’s already being researched as a treatment for many other ailments and disorders— β-thalassemia, severe combined immunodeficiency (SCID)Wiskott-Aldrich syndrome, even HIV — so this one type of technology could end up being something of a panacea for what ails us, as long as what ails us is genetic.

HIV vaccine breakthrough in discovery of ‘on-off switch’


  • Researchers have discovered how to generate an ‘on-off’ switch in a form of HIV
  • HIV needs a specific amino acid to replicate so researchers replaced the code that does this with a ‘nonsense’ version that halts amino acid production
  • When the supply of amino acids stopped, so did the replication
  • This technique gave the team control over the virus’s replication.

A breakthrough has occurred in the fight against HIV, new research reveals.

Scientists say they’ve engineered an ‘on-off switch’ into a weakened form of HIV, enhancing the safety and effectiveness of a potential vaccine for the virus.

They say this could be the final necessary step to eradicate the disease that’s killed 35 million people since the beginning of the epidemic in the 1980s.

Researchers at the University of Nebraska-Lincoln have discovered how to generate an 'on-off switch' into a weakened form of HIV (seen here in the bloodstream)

Researchers at the University of Nebraska-Lincoln have discovered how to generate an ‘on-off switch’ into a weakened form of HIV (seen here in the bloodstream)

Vaccinologists often prefer exposing the body to weakened viruses, rather than deactivated ones, because they grant stronger and longer-lasting immunity.

But weakened viruses retain the ability to replicate, meaning that they still pose a risk of becoming full-blown pathogens.

Researchers at the University of Nebraska-Lincoln began addressing this issue in 2014, when they genetically engineered a version of HIV that needs a synthetic amino acid – one not found in the body – to replicate.

Doing so required the team to replace a codon that codes for the amino acid in the HIV’s genetic code.

NEW COMBINATION OF DRUGS COULD ELIMINATE HIV

HIV could be eliminated using a novel combination of drugs, claims a research team on the brink of an unprecedented experiment.

Scientists at Case Western Reserve University’s medical school have been granted $2.5 million to try pairing two never-before-combined AIDS treatments in a human clinical trial.

The properties – a natural protein that kills disease and a lab-made antibody – have been separately used in HIV-suppressing drugs for years.

Our current line-up of medication is highly effective: roughly 30 percent of America’s 1.2 million people with HIV have reached an undetectable viral load – meaning treatment has suppressed the virus to the point it is untransmittable.

But lead researcher Dr Michael M Lederman believes a combination of these two properties could ‘produce more of a wallop in tandem than when administered individually’.

The team swapped out one of these codons for a ‘nonsense’ version that instead signals a stop in the amino-acid assembly line, halting production of the proteins essential for replication.

When the team supplied the synthetic amino acid, the assembly line began churning out proteins, and the virus began replicating. When the supply of amino acids stopped, so did the replication.

This technique gave the team control over the HIV’s replication. And by delivering a consistent supply of amino acids, the team showed that it can kick-start the multiple cycles of replication necessary for an effective vaccine.

‘Safety is always our biggest concern,’ said Dr Wei Niu, an associate professor of chemical and biomolecular engineering.

‘In this case, [it means] we’re one step closer to generating a vaccine.’

Other research teams have managed to generate HIV immunity in organisms, with one vaccine protecting 95 percent of rhesus monkeys against the virus.

Many of these vaccines have relied on deleting HIV genes to limit replication, but the virus’ penchant for mutating can help it overcome this defense and replicate unchecked.

Dr Qingsheng Li, a professor of biological sciences, said the team’s combination of a nonsense codon, genetic switch and synthetic amino acid represents an especially rigid set of safeguards against unchecked replication.

‘That’s the big milestone,’ said Dr Li.

‘If that works well, we need to go to the pre-clinical animal model before going to a clinical trial. That’s our goal and road map.’

Watch the video discussion. URL:http://www.dailymail.co.uk/health/article-4365848/HIV-vaccine-breakthrough-discovery-switch.html#v-3889855243001

Source:dailymail.co.uk

Lurking HIV detected by scientists in a major biomarker discovery.


Scientists have discovered a unique protein that gives away the presence of inactive HIV in the body.

Sniffing out these hidden caches of the virus is something researchers have been trying to do for decades. Now that we have a lead, the finding could speed up research on a cure.

 Thanks to modern antiretroviral therapies, for many people, HIV is not the death sentence it once was. But we still don’t have a reliable way of permanently flushing it out of someone’s system.

Drugs can keep the virus in check, but unfortunately HIV has a major weapon – it stows away in secret reservoirs in the immune system. There it lies dormant until conditions are more suitable to re-emerge.

That’s why people infected with HIV have to spend a lifetime on expensive drugs, because the virus can take only weeks to come back from its latent state if drug treatment is stopped.

Those nasty secret reservoirs HIV creates are located in long-lived immune cells known as resting T cells. Because the virus hijacks these cells and integrates its genetic material into the DNA of the patient, it makes reservoir T cells extremely hard to track down.

Now a team of French scientists has managed to achieve this important milestone in HIV research by discovering a biomarker that exists only on the surface of T cells that harbour the latent virus.

“Since 1996, the dream has been to kill these nasty cells in hiding, but we had no way to do it because we had no way to recognise them,” says virologist Monsef Benkirane from University of Montpellier in France.

 Benkirane’s team discovered that a specific protein, called CD32a, hangs out on the surface of T cells with a latent HIV infection, but is not found on uninfected T cells, or even T cells with active HIV.

This is huge. Having CD32a as a biomarker for HIV reservoirs means scientists have a better chance to track them down in a patient’s blood. This paves the way for more research into the mechanisms that allow HIV to create such reservoirs in the first place.

Armed with such knowledge, scientists could then find ways to actually get rid of these HIV nests for good.

The team first detected the protein in a lab-made model of HIV infection, before moving on to test it as a biomarker in actual blood samples from 12 people who live with HIV and are receiving treatment.

They separated T cells with CD32a from other T cells in the blood samples, and found that the cells with this particular protein indeed had latent HIV harboured inside them.

Unfortunately, it’s not a smoking gun in every case, since the protein was found only on about half of all latently infected T cells.

Douglas Richman from University of California San Diego, who wasn’t involved in the research, writes that “the eradication of latent HIV would require a much greater reduction in the number of latently infected cells in the body.”

But it’s an extremely encouraging first step in the long search for a marker that could help us track down the nasty virus once it goes into hiding.

Tony Fauci, director of the US National Institute of Allergies and Infectious Disease, told Nature that a good next step would be to replicate the findings in more blood samples from a larger variety of patients who have the virus.

It’s still way too soon to say that we’re on the path to an actual HIV cure, but the news is super-exciting to researchers who have been hammering away at this problem for decades.

“I really hope this is correct,” says Fauci. “The fact that this work has been done by such competent investigators, and the data looks good, makes me optimistic.”

In a world where HIV continues to be a major health issue, this discovery indeed gives cause for optimism.

About 36.7 million people around the world live with HIV, but only 17 million have access to antiretroviral therapy, according to data from the US CDC.

The scientists have already filed a patent for the diagnostic and therapeutic use of the new biomarker.

Soource:Nature.

Lurking HIV Detected by Scientists in a Major Biomarker Discovery


Scientists have discovered a unique protein that gives away the presence of inactive HIV in the body.

Sniffing out these hidden caches of the virus is something researchers have been trying to do for decades. Now that we have a lead, the finding could speed up research on a cure.

 

Thanks to modern antiretroviral therapies, for many people, HIV is not the death sentence it once was. But we still don’t have a reliable way of permanently flushing it out of someone’s system.

Drugs can keep the virus in check, but unfortunately HIV has a major weapon – it stows away in secret reservoirs in the immune system. There it lies dormant until conditions are more suitable to re-emerge.

That’s why people infected with HIV have to spend a lifetime on expensive drugs, because the virus can take only weeks to come back from its latent state if drug treatment is stopped.

Those nasty secret reservoirs HIV creates are located in long-lived immune cells known as resting T cells. Because the virus hijacks these cells and integrates its genetic material into the DNA of the patient, it makes reservoir T cells extremely hard to track down.

Now a team of French scientists has managed to achieve this important milestone in HIV research by discovering a biomarker that exists only on the surface of T cells that harbour the latent virus.

“Since 1996, the dream has been to kill these nasty cells in hiding, but we had no way to do it because we had no way to recognise them,” says virologist Monsef Benkirane from University of Montpellier in France.

 Benkirane’s team discovered that a specific protein, called CD32a, hangs out on the surface of T cells with a latent HIV infection, but is not found on uninfected T cells, or even T cells with active HIV.

This is huge. Having CD32a as a biomarker for HIV reservoirs means scientists have a better chance to track them down in a patient’s blood. This paves the way for more research into the mechanisms that allow HIV to create such reservoirs in the first place.

Armed with such knowledge, scientists could then find ways to actually get rid of these HIV nests for good.

The team first detected the protein in a lab-made model of HIV infection, before moving on to test it as a biomarker in actual blood samples from 12 people who live with HIV and are receiving treatment.

They separated T cells with CD32a from other T cells in the blood samples, and found that the cells with this particular protein indeed had latent HIV harboured inside them.

Unfortunately, it’s not a smoking gun in every case, since the protein was found only on about half of all latently infected T cells.

Douglas Richman from University of California San Diego, who wasn’t involved in the research, writes that “the eradication of latent HIV would require a much greater reduction in the number of latently infected cells in the body.”

But it’s an extremely encouraging first step in the long search for a marker that could help us track down the nasty virus once it goes into hiding.

Tony Fauci, director of the US National Institute of Allergies and Infectious Disease, told Nature that a good next step would be to replicate the findings in more blood samples from a larger variety of patients who have the virus.

It’s still way too soon to say that we’re on the path to an actual HIV cure, but the news is super-exciting to researchers who have been hammering away at this problem for decades.

“I really hope this is correct,” says Fauci. “The fact that this work has been done by such competent investigators, and the data looks good, makes me optimistic.”

In a world where HIV continues to be a major health issue, this discovery indeed gives cause for optimism.

About 36.7 million people around the world live with HIV, but only 17 million have access to antiretroviral therapy, according to data from the US CDC.

The scientists have already filed a patent for the diagnostic and therapeutic use of the new biomarker.

Source:http://www.sciencealert.com

Antibiotics resistance could kill 10 million a year by 2050


A British government-commissioned review has found that resistance to antibiotics could account for 10 million deaths a year and hit global gross domestic product by 2.0 to 3.5 percent by 2050

A British government-commissioned review has found that resistance to antibiotics could account for 10 million deaths a year and hit global gross domestic product by 2.0 to 3.5 percent by 2050

London (AFP) – A British government-commissioned review has found that resistance to antibiotics could account for 10 million deaths a year and hit global gross domestic product by 2.0 to 3.5 percent by 2050.

The Review on Antimicrobial Resistance said surgeries that have become widespread and low-risk thanks to antibiotics, such as caesarean sections, could become more dangerous without urgent action.

The review announced by British Prime Minister David Cameron was led by Jim O’Neill, former chief economist at US investment bank Goldman Sachs, and included British senior public health experts.

It found the region with the highest number of deaths attributable to antimicrobial resistance would be Asia with 4.7 million, followed by Africa with 4.1 million, while there would be 390,000 in Europe and 317,000 in the United States.

For comparison, the review estimated that the second-biggest killer, cancer, would account for 8.2 million deaths a year by 2050.

“The damaging effects of antimicrobial resistance are already manifesting themselves across the world,” the report said.

“Antimicrobial-resistant infections currently claim at least 50,000 lives each year across Europe and the US alone,” it added.

The calculations were based on existing studies by the think tank Rand Europe and the consultancy KPMG.

It warned drug resistance was not “a distant and abstract risk” and called for “a major intervention to avert what threatens to be a devastating burden on the world’s healthcare systems”.

The review emphasised the economic advantage of investment in tackling the problem early.

It said that three types of bacteria — the Klebsiella pneumonia, Escherichia coli (E. coli) and Staphylococcus aureus — were already showing signs of resistance to medicine.

Treatment of HIV, malaria and tuberculosis were broader public health issues in which resistance “is a concern”, the report said.

In the United States, antibiotic-resistant infections are associated with 23,000 deaths and two million illnesses each year.

The economic costs annually are as high as $20 billion (16 billion euros) in excess direct health care costs and $35 billion (28 billion euros) in lost productivity.

WHY IT’S TOO SOON TO SAY HIV HAS BEEN CURED


HIV

HIV is good at hiding inside CD4 T cells in the immune system

A 44-year-old British man was seemingly “cured” of HIV last week. Scientists working on the therapy say that the virus is now completely undetectable in his blood, leading to headlines announcing an “HIV breakthrough” that could “spell the end of the virus”.

But here’s the thing: It’s very difficult to determine whether HIV has been truly eliminated from the body, and even conventional antiretroviral therapy — which the patient was also taking — reduces HIV to undetectable levels. So pinning hopes on a single trial to prove a “cure” is a bit too premature, if optimistic.

The hallmark of an HIV infection is that it targets very specific cells in a patient’s immune system, called CD4 T cells. These are white blood cells that usually detect intruders and corral a larger immune response to get rid of the invading bacteria or viruses. But HIV tricks these frontline soldiers and quickly inserts its own genetic material into the CD4 cells so that it can replicate inside them and use the cells to churn out more copies of virus.

Once infected, cells can’t get rid of HIV the way they can most other viruses. Taking combination antiretroviral therapy, however, stops HIV from reproducing and infecting new CD4 cells. Viral levels start declining and after two to three months of treatment, the levels of virus are so low that HIV is “undetectable” in a patient’s blood, says Janet Siliciano, an infectious disease researcher at Johns Hopkins University.

The problem is that most HIV tests measure the amount of viral RNA in free virus particles floating around in the blood and try to extrapolate the amount of virus hiding inside all infected cells. But in 1995, Siliciano’s lab found that some HIV remains invisible deep inside “resting” CD4 T cells. This silent reservoir can’t be measured by normal blood tests, she says. When people go off antiretroviral therapy, the virus rapidly resurges, and that’s when scientists realize that the virus was hidden somewhere inside the patient all along.

“Everyone has a different number of resting infected cells that are acting as a reservoir. They turn back on randomly, so it’s very hard to predict when someone will experience a viral rebound,” says Siliciano.  That is why people with HIV must take antiretrovirals for the rest of their life, she explains.

The only way to know that HIV has left a person’s body is to test many different tissues — not just run a blood test — and keep repeating them over the years. Siliciano’s group is trying to develop one consolidated test.

Shock and Kill Strategy

One popular strategy in searching for a cure aims to obliterate the reservoir of remaining virus using a “shock and kill” approach. The idea behind it is that shocking the resting CD4 cells into waking up will force the virus inside them to become active as well. As HIV starts to rear its ugly head and put its mark on the surface of the infected cells, scientists can then boost a patient’s immune system to recognize and destroy HIV-carrying cells while they are vulnerable.

This is the technique used in the recent “breakthrough” by British researchers. The scientists, who hail from six different hospital centers in the UK, are testing an aggressive shock and kill regimen on 50 HIV patients over a period of about 9 months. The anonymous patient initially quoted in The Sunday Times is simply the first of the participants to have completed the treatment. Official results from the trial are not expected until 2018.

“I’m surprised that they would announce this in the press when they only have one patient and are not expecting all the results to come in until 2018,” says Stephen Morse, an epidemiologist and director of the Center for Public Health Preparedness at Columbia University. “There has been such a history of false optimism and false hope with HIV that you wonder why announcements like that are made.”

 Even if the trial is a complete success, scientists will have to use caution in interpreting the results, according to Morse. Researchers will need to follow up on patients for several years, testing their viral levels regularly to make sure that HIV is truly eradicated from their system. They’ll also have to conduct a more extensive search for the virus to make sure it isn’t hiding in reservoir cells in the immune system or in other inaccessible parts of the body, such as cerebrospinal fluid or semen, Morse says. “We need a lot of good evidence before we can declare victory over HIV.”

To date, only one person has undergone that kind of rigorous testing. Timothy Ray Brown, who is also known as “the Berlin patient”, is the first and only person who can claim the distinction of being cured of HIV. In 2006, after living with the virus for 11 years and controlling his infection with antiretroviral drugs, Brown learned that he had developed an unrelated case of acute myeloid leukemia. He underwent chemotherapy and whole-body radiation that wiped out his immune system — and possibly the virus with it. Then he received a bone marrow transplant from a donor with a natural immunity to HIV. Researchers haven’t been able to find any trace of HIV in his blood or in multiple brain, gut, colon, and lymph-node biopsies since.

But bone marrow transplants have a high fatality rate, and there are just too many people with HIV — 33 million around the world — to make it a feasible therapy. And they may not even work consistently. Other patients who seemed to have been cured of the virus after receiving bone transplants still experienced a rebound of the virus after ditching their antiretroviral therapy — sometimes after nearly five years of being “HIV-free”.

Any new treatment that successfully eradicates the virus needs to be replicated in larger studies, says Siliciano. It also needs to match or surpass current standards of antiretroviral therapy, in terms of safety and accessibility of the drugs. Scientists also need to develop better, more sensitive assays to test for the presence of HIV. Only then will they be able to say accurately if a treatment is an effective cure for the viral infection.

“It’s a really hard, complex problem, and lots of scientists around the world are trying to work toward a cure,” she says. “But right now we have nothing that’s really close.”

UN Classifies Antibiotic Resistance as a Crisis, Putting It on Par With Ebola and HIV


IN BRIEF

Antibiotic resistance, the ability of bacteria to evolve to combat treatment, has been declared a crisis by the United Nations. The classification will hopefully lead to the funding and research needed to combat, or even fully eradicate, the problem, which is currently responsible for more than 23,000 deaths per year in the U.S. alone.

SUPER DRUG, SUPER BUG

Since Alexander Fleming’s discovery of penicillin in 1928, antibiotics have come to revolutionize medicine in the 20th century. By systematically killing off microbes that cause infections, antibiotics made it easy to cure bacterial infections from wounds as well as highly communicable diseases such as pneumonia, gonorrhea, and syphilis. Along with vaccines, antibiotics have considerably improved the life expectancy of people all over the world.

Here’s the rub: like humans, microbes can adapt.

When exposed to antibiotics frequently enough, bacteria can evolve to combat the treatments. Also known as antibiotic resistance, this phenomenon results in bacteria that is more resistant (if not fully immune) to the drugs that could treat them before. A report from Quartz showed that the U.S. Centers for Disease Control and Prevention (CDC) has estimated that 23,000 people die each year as a direct consequence of antibiotic resistance, and that’s just in the U.S.

The issue is so serious that the United Nations has now elevated the problem of antibiotic resistance to crisis level.

https://embed.ted.com/talks/ramanan_laxminarayan_the_coming_crisis_in_antibiotics

TAKING COLLECTIVE ACTION

The new categorization puts antibiotic resistance on par with Ebola and HIV as a threat to humanity, and while the declaration alone won’t be enough to completely eradicate the problem of antibiotic resistance, it marks a global commitment to combating the issue and saving lives. With 193 member states of the UN General Assembly signing the document, the world is clearly in agreement that action needs to be taken.

As more companies in those countries, particularly those in the pharmaceutical and food industries, adopt policies aimed to reduce the overuse of antibiotics and more research is conducted on the topic, we should see a decrease in the number of deaths related to antibiotic resistance. Perhaps the next ruling the UN makes on the issue will be one in the other direction, from crisis level to problem of the past.

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