Tag: HIV

Categories : HIV PaediatricsTags :

Too Few Children with HIV are Virally Suppressed

On By ModernMedia
Photo by sergey mikheev on Unsplash

Globally, less than two thirds of children and adolescents living with HIV who are receiving treatment are virally suppressed, according to new research published in The Lancet HIV.

Viral suppression [PDF] for HIV means that treatments are protecting health and preventing the transmission of HIV to others. UNAIDS has set a target of achieving 95% viral suppression among all people living with HIV on treatment by 2030.

“We estimate viral suppression one, two and three years after people start taking antiviral treatment, so that we can understand how well the treatments are working over time,” said Professor Matthew Law from the Kirby Institute.

“The data among adults on treatment in our studies show that viral suppression was achieved in an estimated 79% of adults at one year, and 65% at three years. However, viral suppression is poorer among children, at an estimated 64% at one year and 59% at three years.”

Senior study author, Dr Azar Kariminia from the Kirby Institute, said there are unique barriers to achieving viral suppression for children and adolescents. “It can be challenging for them to take treatment regularly, and children rely on caregivers who are often having to manage their own medical needs. There are also a range of factors that stem from stigma and discrimination, including a fear of disclosing the child’s HIV status.”

For this study, the researchers analysed data from 21 594 children/adolescents and 255 662 adults from 148 sites in 31 countries who initiated treatment between 2010 and 2019.

Dr Annette Sohn, from amfAR’s TREAT Asia program, is Co Principal Investigator for IeDEA Asia-Pacific (along with Prof. Law). She says that “while there has been substantial progress in the global response to HIV, the needs of children and adolescents often fall behind those of adults. Our efforts must extend beyond ensuring access to paediatric medicines to address the social and developmental challenges they face in growing up with HIV if we are to achieve the WHO targets by 2030.”

Viral load testing is essential to find out whether HIV treatments are working effectively. It is recommended by WHO at six and 12 months following the initiation of treatment, and then every 12 months thereafter. While viral load testing is common in high-income countries, scaling up accessible viral load testing in resource-limited settings remains a challenge.

With Australian government funding, the Kirby Institute and the Papua New Guinea Institute of Medical Research (PNGIMR) are partnering with the PNG government and a consortium of partners are implementing a program called ‘ACT-UP PNG’ which will scale up HIV viral load testing in two provinces with high HIV rates.

“Our work is ensuring that infants and children are afforded the same access to testing and treatment as other people with HIV,” says Dr Janet Gare from the PNGIMR and a Co-Principal Investigator on ACT-UP-PNG.

Instead of doing viral load testing in distant laboratories, ACT-UP PNG provides same-day molecular point-of-care testing in HIV clinics.

“This brings HIV viral load testing closer to patients, which currently includes children aged 10 and older, and adolescents,” says Dr Gare. “However, we are also pioneering the implementation of a diagnostic platform that will allow the same access to timely HIV viral load testing and results for infants six to eight weeks of age, and children up to nine years, who are currently unable to be included in point-of-care methods.”

Scientia Associate Professor Angela Kelly-Hanku says that these technologies will make testing for viral suppression in infants and children easier.

“We cannot end AIDS without addressing the inequalities that exist between paediatric and adult HIV programs. Projects like ACT-UP make a real difference and bring us closer to achieving the UNAIDS targets.”

Source: University of New South Wales

Categories : HIVTags :

HIV-infected Cells Use Sugars to Avoid Immune Destruction

On By ModernMedia
HIV invading a human cell
HIV invading a human cell: Credit NIH

A new study shows how key features on the surface of HIV-infected cells such as certain sugar molecules help the disease evade detection by the immune system, and how they can be disabled. The findings, published in PLOS Pathogens, represent a first step to eradicating this persistent virus in patients.

“We identified a glyco-immune checkpoint interaction as a novel mechanism that allows HIV-infected cells to evade immune surveillance,” said Mohamed Abdel-Mohsen, PhD, assistant professor in the Vaccine & Immunotherapy Center at The Wistar Institute and coauthor on the paper. “And we developed a novel approach that selectively targets these interactions on the surface of these infected cells.”

Existing treatments can reduce HIV to undetectable levels, but eradication remains elusive, with the disease typically returning quickly when treatment stops. And even when controlled, HIV increases risk for other health problems, including neurological disorders, cardiovascular disease, and cancer.

For the new study, researchers looked at a type of sugar molecule called sialic acid on the surface of HIV-infected cells. These sugars bind with receptors called siglecs on the surface of disease-fighting ‘natural killer’ immune cells. When activated, these receptors act as inhibitors, restraining the killer cells and causing them to stop killing. “We thought, ‘is it possible that these HIV-infected cells are using this interaction – covering themselves with these sugars to evade the natural killer immune surveillance?’” said Prof Abdel-Mohsen.

The researchers found that these infected cells can actually exploit this inhibitory connection to evade immune surveillance. They then investigated whether they could manipulate this connection to make the killer cells more effective at killing HIV-infected cells. Disabling the inhibitors from the killer cells was found to cause the immune cells to attack indiscriminately. The researchers turned to the HIV cells, using the enzyme sialidase to remove the sialic acid sugars that were activating the immune inhibitors but this affected all cells, again causing the killer cells to attack indiscriminately. Finally, they developed a sialidase conjugate linked to HIV antibodies, which only targeted sialic acid on HIV cells. With the sialic acid removed from these cells, the killer immune cells attacked and killed the HIV-infected cells, leaving healthy cells alone.

“The killer cells become a super killer for the HIV-infected cells and they now attack them in a selective manner,” said Prof Abdel-Mohsen. “The discovery could be a missing link in the “shock and kill” approach to HIV treatment that has been a focus of research for the past several years,” he added. This two-step process involves first “shocking” the HIV out of latency so it can be detected, and then stimulating the immune system to “kill” the virus once and for all. However, while effective methods have been discovered to reverse latency, scientists haven’t yet found a way to make HIV-infected cells more killable once reactivated. “We may have the shock, but we don’t yet have the kill,” Prof Abdel-Mohsen said. “Our method actually increases the susceptibility of HIV-infected cells to killing, which is one of the top unmet needs in the HIV field.”

First author Samson Adeniji, Ph.D., a postdoctoral fellow at Wistar, noted that the team’s approach could be tested in combination with broadly neutralizing antibody therapies currently being studied in clinical trials. “By combining approaches, we could turn these immune cells from a cop into a kind of Robocop,” he said.

The researchers also noted that, besides  HIV, the approach could be applied in infectious diseases that may evade the immune system, including hepatitis and COVID. In vivo tests with animals are the next step. They’re also investigating other sugar molecules on HIV that may play a similar role as sialic acid. “HIV-infected cells are likely evading immune surveillance through many potential glyco-immune checkpoints,” Abdel-Mohsen said. “We are investigating other mechanisms and how to break them.”

Source: Wistar Institute

Categories : HIVTags :

Major Mechanism for Chronic Inflammation in HIV Uncovered

On By ModernMedia
HIV invading a human cell
HIV invading a human cell: Credit NIH

In a groundbreaking study of people living with HIV, scientists found that neutrophils play a role in impaired T cell functions and counts, as well as the associated chronic inflammation that is common with the virus.

Neutrophils make up 60–80% of circulating immune cells in the blood. However, these white blood cells are extremely short-lived and cannot be frozen and thawed like other immune cells, making examining them extremely difficult, said study lead Shokrollah Elahi.

“Neutrophils live for hours to a day or two maximum,” Elahi said. “The body produces a lot of neutrophils, and they do their job and then they die and have to be regenerated in the bone marrow. But despite the fact that neutrophils are the most abundant white blood cells in the blood circulation, their role in the context of HIV has not been very well defined.”

In the study, published in the journal PLOS Biology, researchers examined fresh blood samples of 116 people living with HIV and 60 non-infected individuals. They ran comprehensive sequencing on all the genes expressed in the neutrophils from both groups to determine any differences between them.

“We found that not all HIV-infected individuals have similar types of neutrophils,” said Elahi. “As the HIV disease progresses, neutrophils become more activated and more potent, and in turn activate the body’s T cells, which likely causes some of the problems associated with HIV infection such as inflammation and rapid aging.”

Elahi said neutrophils act like an early alarm system: in response to pathogens, they release proteins to signal other immune cells to the danger. This activation can be high or low, or more or less potent, depending on the severity of the danger and the reaction of other immune cells.

One of these proteins is galectin-9, which Elahi previously linked to severe inflammation and cytokine storms in COVID patients. Elahi’s team reported that when neutrophils sense a danger such as an infection, they become stressed and release the galectin-9. As the protein begins to saturate the blood, it can interact with different immune cells. For example, the team found that galectin-9 reacted strongly with T cells and made them more susceptible to HIV infection, causing a cascading effect that leads to a hyper-immune response and inflammation.

Elahi’s prior work showed that patients with HIV and some forms of cancer had elevated levels of galectin-9 in their blood, but now he was able to identify the major source of the protein.

“We found for the very first time that the neutrophil membrane, through a complex mechanism, is covered like a blanket with galectin-9,” he said. “When neutrophils become highly activated, the secretion of galectin-9 can activate T cells through interaction with another molecule called CD44, which then promotes chronic inflammation in HIV patients.”

This ‘alarm’ reaction of shedding proteins such as galectin-9 was linked to oxidative stress, which is believed to play a role in the development of diseases including Parkinson’s, Alzheimer’s, cancer, heart failure and autism.

Based on his findings, Elahi said preventing galectin-9 shedding might be a powerful tool in reducing many of the negative effects of HIV infection. His team has already made some progress in reducing oxidative stress by using an organic antioxidant compound called phloretin and vitamin C.

“We have been looking at phloretin and vitamin C in the lab and our data are very promising,” Elahi said. “We know that both are good at reducing galectin-9 shedding, so we believe they can prevent the hyper-activation of neutrophils. We hope that our results will spark renewed investigation into the role of neutrophils in T cell activation in other acute and chronic conditions.”

Elahi noted the importance of immediate screening tests for HIV or at-risk people, saying: “If the virus is caught early and they can go on antiretroviral therapy, then it stops disease progression and reduces many of the complications associated with advanced HIV.”

Source: University of Alberta Faculty of Medicine & Dentistry

Categories : COVID HIVTags :

AstraZeneca Vaccine Confers COVID Protection for People with HIV

On By ModernMedia
Image by Ivan Diaz on Unsplash

Interim results from a phase 1B/2A clinical trial conducted by the Wits Vaccines and Infectious Diseases Analytical (VIDA) research unit showed that the AstraZeneca vaccine conferred COVID protection in people living with HIV.

The findings, published in Lancet HIV, show that the AstraZeneca COIVD vaccine is likely to work as well in people living with HIV compared with people who are HIV negative.

These interim findings are vital for informing the clinical management of people with HIV during the COVID pandemic.

In general, clinical trials which evaluate the safety and immunogenicity of COVID vaccines in people living with HIV are limited, and in Africa they are virtually non-existent. This is despite the overwhelming prevalence of HIV infection in Africa, especially South Africa .

“We searched PubMed for peer-reviewed articles published between 1 January 2019 and 29 June 2021, using the terms ‘safety’ and ‘Covid-19’ and ‘vaccine’, but we did not find any reports that evaluated safety and immunogenicity of COVID vaccines in this population,” said Shabir Madhi, Professor of Vaccinology and Director of Wits VIDA, which led the first South African trial for a COVID vaccine in June 2020.

Compared to the general population, people living with HIV have an increased risk of infectious diseases and have a greater mortality risk when hospitalised with severe COVID.

In addition, compared with HIV-negative individuals, people with HIV are at greater risk for infectious diseases, such as influenza, including during antiretroviral therapy (ART).

Risk factors for severe COVID in people with HIV include more advanced stage of HIV/AIDS, the HIV-1 infection not being virally suppressed, and CD4 counts below 500 cells per microlitre.

The study was an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial. In 2020, the trial enrolled 104 people living with HIV were enrolled in the trial, HIV-negative people. Eligibility criteria for people with HIV included being on ART for at least three months, with a plasma HIV viral load of less than 1000 copies per microlitre.

The HIV study was a unique addition to the AstraZeneca COVID vaccine clinical trial, and aimed to assess safety and immunogenicity of this vaccine in people with HIV and HIV-negative people in South Africa. The primary endpoint in all participants regardless of HIV status was the safety, tolerability, and reactogenicity profile of the AstraZeneca COVID vaccine.

Reactogenicity refers to a subset of reactions that occur soon after vaccination, and are a physical manifestation of the inflammatory response to vaccination. Such symptoms include pain, redness, swelling or induration for injected vaccines, and systemic symptoms, such as fever, myalgia, headache, or rash. In clinical trials, information on expected signs and symptoms after vaccination is actively sought.

The interim findings show that the AstraZeneca COVID vaccine was well tolerated and showed favourable safety and immunogenicity in people with HIV, including heightened immunogenicity in SARS-CoV-2 baseline-seropositive participants.

Source: University of the Witwatersrand

Categories : HIV VaccinesTags :

J&J HIV Vaccine Fails in Local Trials

On By ModernMedia
HIV invading a human cell
HIV invading a human cell: Credit NIH

Johnson & Johnson and its partners announced preliminary results showing their HIV vaccine trial failed to provide sufficient protection against HIV infection in a population of young women in sub-Saharan Africa.

The vaccine had a favourable safety profile with no serious adverse events.
The Phase 2b HIV vaccine clinical trial was known as the Imbokodo study (also known as HVTN 705/HPX2008), which will now be discontinued. Further analysis of the Imbokodo study is ongoing, and the study has provided enough data to progress with key immunological correlates research.

“The high incidence of HIV among young women in sub-Saharan Africa reminds us that, despite great progress made in treatment and prevention, HIV remains a major health challenge for the region,” said Professor Glenda Gray, President and Chief Executive Officer, South African Medical Research Council (SAMRC) and Imbokodo’s Protocol Chair. “This underscores the need to apply the knowledge that will be gained from this trial to continue to advance the pursuit of a global HIV vaccine.”A parallel, ongoing Phase 3 Mosaico study (HVTN 706/HPX3002) with men who have sex with men and transgender individuals in Europe and Americas will continue due to the different HIV strains that are circulating in the trial areas and the different HIV vaccine regimen.
The HIV regimen consisted of an adenovirus vector containing four mosaic immunogens (Ad26.Mos4.HIV) at four vaccination visits over one year. The Imbokodo regimen contains a soluble protein component (Clade C gp140, adjuvanted with aluminum phosphate) which is administered at vaccination visits three and four. The ongoing Phase 3 Mosaico study is testing a different investigational vaccine regimen that involves the administration of a mosaic-based mixture of soluble proteins (Clade C/Mosaic gp140) at vaccination visits three and four.

Imbokodo participants had four vaccination visits over one year, with the primary endpoint based on new HIV infections through month 24. These data found that 63 of 1109 placebo arm participants compared to 51 of 1079 vaccine arm participants. This analysis demonstrated a vaccine efficacy point estimate of 25.2% (95% confidence interval of -10.5% to 49.3%).

HIV is prevalent in Sub-Saharan Africa, where women and girls accounted for 63 percent of all new HIV infections in 2020. The study enrolled roughly 2600 young women across Malawi, Mozambique, South Africa, Zambia and Zimbabwe. Researchers ensured that any HIV-infected participants in Imbokodo were referred to high-quality HIV treatment and care services. 

Source: PR Newswire

Categories : HIVTags :

Inconsistent PrEP Use for HIV in High-risk Groups

On By ModernMedia
HIV infecting a human cell. Credit: Seth Pincus, Elizabeth Fischer and Austin Athman, National Institute of Allergy and Infectious Diseases/NIH

A large, in-depth look at US patients taking HIV-prevention drug therapy found strong adherence soon after patients get the prescription, but less consistent use thereafter, particularly among groups considered to be high-priority.

The study, published in JAMA Network Open, examined data from 13 906 members of Kaiser Permanente referred for pre-exposure prophylaxis, or PrEP, therapy between 2012 and 2019. The study found certain groups were more likely to stop taking PrEP: young people, Black and Latino individuals, women, and people with substance use disorders.

The findings suggest targeted strategies are needed to support use of this effective prevention in high-risk groups, said lead author Carlo Hojilla, RN, PhD, a research fellow with the Kaiser Permanente Northern California Division of Research.

“The findings have important implications that suggest access to health care is a great way to get people in the door, but we need more effective strategies for making sure people who have an ongoing need for PrEP stay on the medication,” said Dr Hojilla. “These are groups we want to reach, and we need innovative approaches to keep them engaged in PrEP care.”

Some 88% of patients referred for HIV prevention care received a PrEP prescription, and most (98%) of them filled their initial prescriptions. “These findings were encouraging,” Dr Hojilla said. “Kaiser Permanente has managed to do really well increasing uptake of PrEP therapy.”
However, significant inconsistency in use was seen with about half of users discontinuing PrEP at least once; 60% of those filled a prescription again though the study did not explore the reasons for this. Some users may have discontinued PrEP because of a decrease in risk for HIV acquisition, the authors speculated. Medical mistrust, stigma, homophobia, and transphobia as barriers to PrEP uptake and persistence in some communities have been documented in prior studies. Cost was known to be a concern for some, and the study was done before PrEP was provided at no cost, Dr Hojilla said.

The study was also done before the introduction of a new dosing scheme known as 2-1-1, or on-demand, which allows the user to take PrEP only around the time of a potential exposure to HIV, with a similar level of effectiveness as daily dosing. It’s possible that some of the discontinuation reflected in the study was from patients who opted to not take the drug daily because they had only occasional risk exposure, even prior to 2-1-1 dosing being formally recommended, said senior author Jonathan Volk, MD, an infectious disease specialist with The Permanente Medical Group.

No new HIV infections were seen in those remaining on PrEP, the study found. “This shows how incredibly well PrEP works when taken,” Dr Volk said. “But there are important opportunities for us to maximise the population level impact of this vital therapy. To do this, we need to avoid attrition along the care continuum, especially by assisting patients to stay on PrEP throughout periods of risk for HIV acquisition.”

Source: Kaiser Permanente

Categories : Diseases, Syndromes and Conditions HIV UncategorizedTags :

High Burden of Uncontrolled Disease in KwaZulu-Natal

On By ModernMedia
Photo by Hush Naidoo on Unsplash

A comprehensive health-screening program has found a high burden of poorly controlled or uncontrolled disease KwaZulu-Natal, along with a high incidence of undiagnosed diseases.

The study, published in The Lancet Global Health, found that four out of five women over 30 had a chronic health condition, and that the HIV-negative population and older people had the highest burden of undiagnosed or poorly controlled non-communicable diseases such as diabetes and hypertension. The study was conducted at the Africa Health Research Institute (AHRI).

Study co-leader Emily Wong, MD, at AHRI in Durban, said: “The data will give AHRI researchers and the Department of Health critical indicators for where the most urgent interventions are needed,” Dr Wong said. “The research was done before COVID, but it has highlighted the urgency of diagnosing and treating people with non-communicable diseases — given that people with uncontrolled diabetes and hypertension are at higher risk of getting very ill with COVID.” 

HIV-associated tuberculosis infections are particularly prevalent in Durban. Dr Wong of the University of Alabama works there to understand the impact of HIV infection on tuberculosis pathogenesis, immunity and epidemiology. In sub-Saharan Africa, 15 years of intense public health efforts that increased access to antiretroviral therapy has resulted in decreased AIDS mortality and raised life expectancy. As a result, there is an increasing priority to address other causes of disease, including tuberculosis and non-communicable diseases.

Over 18 months, health workers screened 17 118 people aged 15 years and older via mobile camps within 1 kilometre of each participant’s home in the uMkhanyakude district. They found high and overlapping burdens of HIV, tuberculosis, diabetes and hypertension among men and women.

While the HIV cases were largely well diagnosed and treated, some demographic groups  still had high rates of undiagnosed and untreated HIV, such as men in their 20s and 30s. In contrast, the majority of people with tuberculosis, diabetes or hypertension were either undiagnosed or not well controlled. Of particular concern was the high rates of undiagnosed and asymptomatic tuberculosis discovered, as it remains one of the leading causes of death in South Africa.

“Our findings suggest that the massive efforts of the past 15 years to test and treat for HIV have done very well for that one disease,” Dr Wong said. “But in that process, we may have neglected some of the other important diseases that are highly prevalent.”

The mobile camps screened for diabetes, high blood pressure, nutritional status (obesity and malnutrition), and tobacco and alcohol use, as well as HIV and tuberculosis. The tuberculosis screening component included high-quality digital chest X-rays and sputum tests for people who reported symptoms or had abnormal X-rays. Clinical information was combined with 20 years of population data from AHRI’s health and demographic surveillance research. Using a sophisticated data system combined with artificial intelligence to interpret the chest X-rays, AHRI’s clinical team examined the information in real time, referring people to the public health system as needed.

The study found that: 

  • Half of the participants had at least one active disease, and 12 percent had two or more diseases. Diabetes and hypertension incidences were 8.5 percent and 23 percent, respectively.
  • One-third of the people were living with HIV, but this was mostly well diagnosed and treated. A particularly high burden of HIV, high blood pressure and diabetes was seen in women.
  • For tuberculosis, 1.4 percent of the people had active disease, and 22 percent had lifetime disease. About 80 percent of the undiagnosed tuberculosis was asymptomatic, with higher rates of active tuberculosis seen in men.
  • Several disease patterns varied by geographical location — eg, the highest HIV burden was seen near main roads, while higher rates of tuberculosis and non-communicable diseases were seen in more remote areas.

Source: University of Alabama at Birmingham

Journal information: Wong, E. B., et al. (2021) Convergence of infectious and non-communicable disease epidemics in rural South Africa: a cross-sectional, population-based multimorbidity study. The Lancet Global Health. doi.org/10.1016/S2214-109X(21)00176-5.

Categories : COVID HIVTags :

HIV Increases Risk of COVID Infection and Mortality

On By ModernMedia
Man with red HIV ribbon on shirt. Photo by Anna Shvets from Pexels

New research shows that individuals living with HIV and AIDS have an increased risk of SARS-CoV-2 infection and death from COVID.

An estimated 38 million people around the world are living with HIV/AIDS, according to the World Health Organization, 7.5 million of whom are in South Africa, according to UNAIDS.

In their review, researchers at  Penn State College of Medicine found that people living with HIV had a 24% higher risk of SARS-CoV-2 infection and a 78% higher risk of death from COVID than people without HIV. They analysed data from 22 prior studies with nearly 21 million participants in North America, Africa, Europe and Asia to determine to what extent people living with HIV/AIDS are susceptible to SARS-CoV-2 infection and death from COVID.

Participants were mostly male (66%) and the median age was 56. The most common comorbidities among the HIV-positive population were hypertension, diabetes, chronic obstructive pulmonary disease and chronic kidney disease. Most patients (96%) were on antiretroviral therapy (ART).

“Previous studies were inconclusive on whether or not HIV is a risk factor for susceptibility to SARS-CoV-2 infection and poor outcomes in populations with COVID-19,” said Dr Paddy Ssentongo, lead researcher and assistant professor at the Penn State Center for Neural Engineering. “This is because a vast majority of people living with HIV/AIDS are on ART, some of which have been used experimentally to treat COVID-19.”

Pre-existing conditions common among people living with HIV/AIDS, may contribute to the severity of their COVID infections, noted the investigators. It remains inconclusive as to whether antiviral drugs, such as tenofovir and protease-inhibitors, reduce the risk of SARS-CoV-2 infection and death from COVID in people with living with HIV/AIDS.

“As the pandemic has evolved, we’ve obtained sufficient information to characterize the epidemiology of HIV/SARS-CoV-2 coinfection, which could not be done at the beginning of the pandemic due to scarcity of data,” said Vernon Chinchilli, fellow researcher and chair of the Department of Public Health Sciences. “Our findings support the current Centers for Disease Control and Prevention guidance to prioritize persons living with HIV to receive a COVID-19 vaccine.”

Source: Penn State University

Categories : HIVTags :

HIV Cure A Step Closer With Rare Immune System Discovery

On By ModernMedia
Photo by CDC on Unsplash

Scientists have taken a step closer to understanding how some rare people’s immune systems can suppress HIV.

The innate immune response mounts a fast-acting, general response against pathogens or supports the adaptive immune response, made up of antibodies and T cells that learn to fight specific pathogens after infection or vaccination

In recent years, researchers discovered that some components of the innate immune response can, under certain conditions, also be trained in response to infectious pathogens, such as HIV. 

In a study recently published in the Journal of Clinical Investigation, it was shown that elite controllers, a rare subset of people whose immune system can control HIV without the use of drugs, have myeloid dendritic cells, part of the innate immune response, that display traits of a trained innate immune cell.

“Using RNA-sequencing technology, we were able to identify one long-noncoding RNA called MIR4435-2HG that was present at a higher level in elite controllers’ myeloid dendritic cells, which have enhanced immune and metabolic states,” explained Xu Yu, MD, a Core Member of the Ragon Institute of MGH, MIT and Harvard. “Our research shows that MIR4435-2HG might be an important driver of this enhanced state, indicating a trained response.”

Myeloid dendritic cells’ main role is the support of T cells, which are key to the elite controllers’ ability to control HIV infection. Since MIR4435-2HG was found to be higher only in the cells of elite controllers, Dr Yu explained, it may be part of a learned immune response to infection with HIV. Myeloid dendritic cells with elevated MIR4435-2HG also had greater levels of a protein known as RPTOR, which drives metabolism. Because of this boosted metabolism, the myeloid dendritic cells may better support the T cells controlling the HIV infection.

“We used a novel sequencing technology, called CUT&RUN, to study the DNA of these cells,” says postdoctoral fellow Ciputra Hartana, MD, Ph.D., the paper’s first author. “It allowed us to study epigenetic modifications like MIR4435-2HG, which are molecules that bind to the DNA and change how, or if, the DNA is read by the cell’s machinery.”

The team found that MIR4435-2HG’s mechanism could function by attaching to the DNA near the location of the RPTOR gene. The bound MIR4435-2HG would then prompt cellular machinery to synthesise more RPTOR protein, from the instructions in the RPTOR gene. This kind of epigenetic modification, a ‘trained’ response to HIV infection, would keep the myeloid dendritic cells in a state of heightened metabolism, providing long-term support to the T cells battling the virus.

“Myeloid dendritic cells are very rare immune cells, accounting for only 0.1-0.3% of cells found in human blood,” said Dr Yu. “We were fortunate and thankful to have access to hundreds of millions of blood cells from the many study participants who have donated their blood to support our HIV research. These donations were key to making this discovery.”

A core component of HIV cure research is to figure out exactly how elite controllers’ immune systems can keep HIV under control. By understanding how elite controllers keep the deadly virus in check, scientists could develop treatments to enable other people living with HIV to replicate the same immune response. This would take away the need for daily medication to control the virus, achieving what is known as a ‘functional cure’.

Source: Medical Xpress

Journal information: Ciputra Adijaya Hartana et al, Long noncoding RNA MIR4435-2HG enhances metabolic function of myeloid dendritic cells from HIV-1 elite controllers, Journal of Clinical Investigation (2021). DOI: 10.1172/JCI146136

Categories : HIVTags :

People Most in Need of PrEP Don’t Use It

On By ModernMedia

Though sexual minority men and transgender women are aware of pre-exposure prophylaxis (PrEP), a daily pill to prevent HIV infection, few are currently taking it, a New York-based study has found.

The study, published in the journal AIDS and Behavior, surveyed 202 young sexual minority men and transgender women, who are two high-priority populations for HIV prevention, to better understand the factors in their taking PrEP or not.

According to the Centers for Disease Control and Prevention, sexual minority men are the community most impacted by HIV, making up 69% of all new diagnoses in 2018, and transgender populations are disproportionately affected by HIV and prevention challenges. While Black and Hispanic populations are mostly likely to be newly diagnosed with HIV, PrEP users are more likely to be white.

The research team, who is from the Rutgers School of Public Health’s Center for Health, Identity, Behavior and Prevention Studies (CHIBPS), found that while 98 percent of the study’s participants were aware of PrEP, less than 25 percent were currently taking it.

“It was surprising that so few participants were using PrEP, but we were happy to see that there were no racial or ethnic disparities in who was using it,” Caleb LoSchiavo, Study Co-Author and Doctoral Candidate, School of Public Health, Rutgers University. “I think the study results point to the effectiveness of local efforts to increase the use of PrEP for those who need it most.”

While the study PrEP found no differences in use use, it also found racial and ethnic differences in factors associated with taking it. White participants were more likely to use PrEP with increased age, and were less likely to use it if they held concerns about daily medication use. Participants of colour, however, were more likely to use PrEP if they received information about it from a health care provider and if they had more positive beliefs about its use.

“Our study highlights the importance of clinicians in expanding the use of HIV prevention methods like PrEP among those who need it most, both through informing their patients about PrEP and through combating stigmatizing beliefs about PrEP use,” said senior study author Perry N Halkitis, dean of the Rutgers School of Public Health and director of CHIBPS.

The researchers said that the study emphasised the importance of PrEP education in clinical settings.

“Positive public health messaging about PrEP must reframe risk, combat stigma and normalize preventive healthcare,” LoSchiavo said.

Source: News-Medical.Net

Journal information: Jaiswal, J., et al. (2021) Correlates of PrEP Uptake Among Young Sexual Minority Men and Transgender Women in New York City: The Need to Reframe “Risk” Messaging and Normalize Preventative Health. AIDS and Behavior. doi.org/10.1007/s10461-021-03254-4.