Caitlyn Fitzpatrick

Even macrophages—an altered white blood cell that becomes an important part of the immune system when an infection is detected&mdash;aren’t safe from HIV.

Researchers first discovered that HIV can infiltrate macrophages in the 1980s, but the topic didn’t come to the forefront until a few years ago. In a new study, a team from the University College London (UCL) found that although macrophages have a protein that shields them, the virus is able to make it past the defense.

The protective protein, SAMHD1, acts as an antiviral and inhibits HIV replication.

“Other viruses can disable SAMHD1, but HIV cannot,” lead author, Petra Mlcochova, a post doc at UCL’s Division of Infection & Immunity, said in a news release. “Our work explains how HIV can still infect macrophages, which are disabling SAMHD1 by themselves.”

Although HIV can’t disable SAMHD1, the UCL team found that the protein’s antiviral protection stops when the protein is switched off. But how does SAMHD1 get switched off? And why? Those answers are unclear, but the researchers speculate that it happens when macrophages perform the natural function of repairing damaged DNA.

“We knew that SAMHD1 is switched off when cells multiple, but macrophages do not multiple so it seemed unlikely that SAMHD1 would be switched off in these cells,” said senior author, Ravindra Gupta, MPH, BM, a professor at the division.

“And yet we found there’s a window of opportunity when SAMD1 is disabled as part of a regularly-occurring process in macrophages,” he noted.

When a macrophage becomes infected with HIV, it continues to produce the virus. This may not be an issue in most patients with HIV, Gupta explained, but focusing on macrophages could help lead researchers to a cure.

 even when the virus is undetectable in the blood. The brain also has macrophages, in the form of microglia. Many infected brain cells are this type of macrophage, which further makes a case for developing treatments with the white blood cell macrophages in mind.

Previous research has shown that histone deacetylase (HDAC) inhibitors, which are sometimes used to treat cancer, can 

 in order to perform a “shock and kill” strategy. In another part of the UCL study, the researchers explored the use of HDAC inhibitors for HIV in human cells 

 and mouse brain tissues. They found that macrophages responded to the inhibitors, showing that the drugs could help inhibit the virus’ opportunity to infect macrophages.

“While this is a barrier to achieving control of HIV in just a minority of patients, it may more importantly be a barrier to a cure,” Gupta concluded.

, “A G1-like state allows HIV-1 to bypass SAMHD1 restriction in macrophages,” was published in 

Articles

Even macrophages arenâ€™t safe from HIV.

How HIV Can Infect Macrophages

Physicians are discovering social media platforms can be used to reach patients and raise awareness of health conditions.

Investigators from the University of Pennsylvania’s Perelman School of Medicine have found that Twitter and Facebook can help identify behavioral trends and attitudes relevant to the risk of infection with HIV.

“The language that we write is a representation of our daily lives,” H. Andrew Schwartz, PhD, said in a news release. “It captures aspects of people that are otherwise quite elusive to health researchers, such as the psychological side that’s difficult to get at.”

Schwartz and colleagues have been examining the impact of social media on HIV for quite some time. Last year they reported in 

 that people living in counties with lower HIV rates were more likely to use action words in their tweets, such as “work,” “plan,” and “engage.”

This finding was based on analyzing more than 150 million tweets from people in the United States. These tweets didn’t directly indicate whether a person was HIV-positive or was planning to get tested for the virus, but the researchers were able to identify general language that corresponded with HIV cases.

The researchers have expanded the discussion on their 

 page. The project aims to use social media in order to identify HIV transmission behaviors, as well as other sexually transmitted infections (STIs).

“To combat HIV effectively, we need to know where treatment resources need to be aimed at and where new health risks are developing,” the team wrote on the group page. “One challenge is that communities’ and individuals’ risk factors for HIV change dynamically and it usually takes several years for these changes to show up in the large surveys that government agencies publish.”

Based on the results from the Health and Social Media Group project, the team is hoping to find specific geographic locations where people are at risk for HIV, which will signal where to implement preventive efforts. This approach is also being used to examine other health conditions, like diabetes. The study findings are expected later this year.

“This type of data can inform public health interventions,” Schwartz, a visiting assistant professor of Computer and Information Science at the University of Pennsylvania and assistant professor of Computer Science at Stony Brook University. “With this information, you can use a ranking of how action-oriented a community is and where you may want to intervene, and start some programs about HIV awareness.”

Social media can identify behavioral trends and attitudes relevant to the risk of infection with HIV.

Social Media Helps Track HIV Transmission Rates

Conflicts of interest (COI) among committee members who set hepatitis C treatment guidelines could be influencing the selection of these suggested rules, according to a new study in the 

Journal of the American Medical Association

Clinical hepatitis C guidelines describe protocols on testing, management, treatment, and additional aspects of the disease. They are meant to be evidence-based and free from bias.

Akilah Jefferson, MD, MSc, and Steven Pearson, MD, MSc, set out to see if the Institute of Medicine’s (IOM) standards for managing conflicts were met in the final September 2015 print version of the hepatitis C virus guideline. The physicians analyzed whether the guidelines met IOM COI standards based on the 

Clinical Practice Guidelines We Can Trust

No commercial COI among guideline committee chairs and co-chairs

Less than 50% of committee members have commercial COI

Jefferson and Pearson looked at disclosure statements to determine if guidelines were adhering to those standards. They used evidence from the 2014 American Association for the Study of Liver Diseases and Infectious Diseases Society of America hepatitis C management guidelines.

“Little is known regarding whether IOM standards for managing COI have been met in development of recent important clinical guidelines,” the team wrote in 

There was a total of 29 committee members involved in deciding the hepatitis C guidelines. Of those:

18 members (62%) disclosed industry-sponsored research

10 members (34%) served on advisory boards

Five members (17%) served on data safety monitoring boards

Three members (10%) reported other honoraria

Four co-chairs (67%) had commercial COI and had additional COI in other publications which were not revealed in the disclosures

The researchers also discovered that another co-chair had a commercial COI.

The hepatitis C guideline met all nine of the IOM guideline for development and evidence standards. However, it did not fully meet standards for commercial COI management. It was common for committee member disclosures to be inconsistent in guidelines disclosures and contemporaneous articles.

“Adoption of consistent COI frameworks across specialty societies may help ensure that clinical guidelines are developed in a transparent and trustworthy manner,” the physicians concluded.

The IOM is one division of the National Academies of Sciences, Engineering, and Medicine, which is made up of private, nonprofit institutions.

, “Conflict of Interest in Seminal Hepatitis C Virus and Cholesterol Management Guidelines,” was published in the 

Conflicts of interest among committee members who set hepatitis C treatment guidelines may influence decision-making.

Conflicts of Interest Persist in Hepatitis C Treatment Guidelines

People with certain mental illnesses may be up to 15 times more likely to have HIV, but they aren’t getting tested for the virus that much more than the general population, according to a new study from the University of California, San Francisco (UCSF).

Data have indicated that 1.8% to 6% of people with severe mental illness have HIV. The CDC found that 0.4% of Americans have HIV. This imbalance can at least be partially tied to the fact that severe mental illness can lead people to engage in risky behavior.

“This includes engaging in unprotected sex with HIV-positive partners of unknown HIV status, injecting drugs, using substances in the context of sexual activity, and episodes of sexual violence,” first author, Christina Mangurian, MD, MAS, of UCSF’s Department of Psychiatry, explained in a news release.

The researchers examined 56,895 Medicaid records in California from October 2010 to September 2011. The patients ranged from aged 18 to 67 years, and had been prescribed at least 1 antipsychotic medication. Mental illnesses included bipolar disorder, schizophrenia, and major depression with psychosis.

Over the course of the study, 6.7% of patients had undergone HIV testing. Through self-reported data, it was found that 5.2% of California residents were tested. More people with mental illness were tested, but not by a large enough margin, given the increased HIV risk they face, the researchers said. Race was a strong predictor of testing. Asians and Pacific Islanders were 53% and African Americans were 82% less likely to be tested for HIV compared with Caucasians.

In addition, men were 32% less likely to be tested compared with women. There was some good news in the findings. People with drug or alcohol use disorders were more likely to be tested for HIV. That’s a positive since substance abuse puts people at risk for infection. The strongest predictor of HIV testing, the researchers wrote in 

, was the utilization of non-psychiatric medical care. Those who received such care were twice as likely to be tested.

“Previous studies have found that people with severe mental illness die up to 25 years earlier than the general population,” Mangurian said. “This is a missed prevention opportunity to detect HIV early in the course of illness.”

It has been recognized that early death in this population is typically from heart disease, tied to anti-psychotic drugs’ increased risk of obesity, diabetes, and high blood pressure. However, other diseases like HIV contribute to the mortality rate, the team noted. The majority of people with severe mental illness were not tested for HIV during the 1-year study.

Although the CDC does not specifically say that annual HIV tests are necessary for the general population, testing is recommended for those who inject drugs and for men who have sex with men. The researchers noted that compliance to antiretroviral therapies (ART) was not an issue among the population.

“People with severe mental illness often have low rates of primary care use, but do seek care at community mental health care clinics,” said senior author, James Dilley, MD, of UCSF’s Department of Psychiatry and the UCSF Alliance Health Project. “As such, we believe this is an excellent opportunity for community psychiatrists to help promote their patients’ health by making HIV testing a part of their care.”

Risky sexual behavior increases the rate of HIV transmission among at-risk populations.

HIV Screening Among Mentally Ill Remains a Problem

A specific neuron protein plays an important role in dementia associated with AIDS, a collaborative team from Cardiff University in Wales, United Kingdom and the University of California, Los Angeles (UCLA) has found. Dementia is one of the most prevalent complications among patients with late HIV-1.

The virus has the ability to cross the blood-brain barrier, which is why it can interfere with brain tissue. Around 30% of adults and 50% of infants with HIV experience cognitive deficits, and in the past it was thought that AIDS-related dementia was caused indirectly by HIV hurting immune cells.

C-C chemokine receptor type 5 (CCR5) has been explored in relation to HIV-1 for quite some time. However, researchers haven’t known how it impacts learning and memory. In this recent study, the Cardiff-UCLA team made a breakthrough in understanding how the neuron protein comes into play.

Interestingly, this research came about almost accidentally. When analyzing the behavior of mice at UCLA, the researchers found that some had better memories. It turns out that the animals that lacked CCR5 proteins in their neurons had these better memories. In contrast, the mice with over-expressed CCR5 protein learned at a slower pace.

“Our findings signal a major turnaround on how we imagine treating cognitive problems associated with AIDS,” Miou Zhou, PhD, a UCLA scientist, said in a news release.

Previous research already showed AIDS uses CCR5 to infect immune cells, but the researchers went a step further.  Treating the mice’s brains, they introduced the part of HIV which attaches to CCR5. This resulted in worse learning and memory.

“I am still amazed that mice without CCR5 can have much better memory than normal mice,” said Alcino Silva, PhD, professor of neurobiology and psychiatry at UCLA.

These findings indicate that HIV increases the natural levels of CCR5 while inhibiting cells from plasticity function—resulting in AIDS-related dementia.

“Armed with the new knowledge that the CCR5 protein in neurons affects learning and plays a major role in AIDS-related dementia, we can now look at ways to suppress it for treatment of the disease and investigate whether its reduction can also benefit other forms of dementia and even aid recovery for stroke victims,” said Kevin Fox, PhD, a professor at Cardiff University.

There’s already a variety of CCR5 receptor antagonists on the market, such as enfuvirtide (Fuzeon) and maraviroc (Selzentry). So while novel therapies could be developed with this new information, it’s good to know that there are readily available options.

“With the available CCR5 drugs on the market this work could have broad and immediate applicability across a range of neurological diseases,” concluded Stuart Greenhill, PhD, of Aston University.

The study, “CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory,” was published in 

	More resources pertaining to Alzheimer’s disease and dementia can be found on 

Dementia is one of the most prevalent complications among patients with late-stage HIV.

Solving the Puzzle of AIDS-Related Dementia

Unprotected sexual exposure to HIV does not necessarily lead to infection. In fact, some studies have gone as far as to say that successful HIV-1 transmission occurs only 1 of 1000 times.

HIV does not have it easy when trying to establish a new infection. Between genital mucosa, tightly packed epithelial cells, and initial immune responses, there are a number of innate barriers to overcome. But even still, thousands of new infections occur in the United States every year.

As Beatrice Hahn, MD, asked, “What is unique about these transmitted viruses that make it this far?” That’s what she, along with colleagues at the University of Pennsylvania set out to understand.

The researchers examined blood and genital secretions from 4 donors with HIV-1 fully suppressed by antiretroviral therapy (ART) and their matched recipients. They were able to generate 300 virus isolates from individual HIV-1 particles and identify characteristics of the virus strains. This allowed the team to see how the virus got around the genital mucosa, which is meant to block intruders.

It turns out that there’s a sub-population of HIV-1 strains that are naturally predisposed to better establish new infections.

Viruses isolated from the recipients were 3 times more infectious and able to replicated 1.4 higher than those gathered from the donors. In addition, these viruses were much more resistant to two type 1 interferons, IFN-beta and IFN-alpha2—requiring 8-fold and 39-fold higher concentrations, respectively, in order to reduce replication by 50%.

“Knowing the viral properties that confer the ability to transmit despite all of the human body’s barriers to infection, might aid the development of vaccines against HIV-1,” said Hahn, a professor of Medicine and Microbiology in the Perelman School of Medicine at Penn.

Furthermore, the viruses from the recipients were released from infected CD4 immune cells. This indicates that cell-free particle production is key in HIV-1 transmission, the researchers explained.

“This means that rapidly multiplying strains of HIV-1 that are interferon resistant have an increased transmission fitness,” said co-first author Shilpa Iyer, a doctoral student in the Han lab.

A final piece of this research suggests that a virus is less likely to replicate properly with larger clones of proviral sequences.

“But we still don’t know which viral gene products render HIV-1 resistant to interferon and how they function. The next steps will be to dissect these mechanisms to define possible new targets for AIDS prevention and therapy,” Hahn concluded.

, “Paired quantitative and qualitative assessment of the replication-competent HIV-1 reservoir and comparison with integrated proviral DNA,” was published in the 

Proceedings of the National Academy of Sciences

 and side photo was provided by the University of Pennsylvania.

Unprotected sexual exposure to HIV does not necessarily lead to infection.