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Smoking HIV out of dormancy

Little bits of virus can lie dormant in immune cells for years, so that if patients stop taking the drugs, the dormant virus can come out of hiding and re-infect the patient.

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Ever since antiretroviral treatments against HIV infection were introduced in 1996, scientists have eagerly been hunting for a cure for the disease.

Although drugs can allow people infected with HIV to live normal, healthy lives, people infected by HIV have to take antiretroviral treatments for as long as they live. Little bits of virus can lie dormant in immune cells for years, so that if patients stop taking the drugs, the dormant virus can come out of hiding and re-infect the patient.

And now, as the first people to start taking this treatment are entering middle or old age, doctors are seeing side effects from inflammation that are caused by having even tiny amounts of HIV in your blood. That’s yet another reason for developing a cure for the disease.

Now, researchers from the Norwegian University of Science and Technology’s (NTNU) Centre of Molecular Inflammation Research (CEMIR) have uncovered a previously unknown way in which the body’s immune system can detect and respond to HIV infection — which could help improve the chances of developing a cure.

Their results have been published in Nature Communications.

To understand exactly what the researchers did requires a refresher course in how HIV actually works inside the body and how the body responds.

When the virus gets into the body, it infects the very cells that the body would use to combat it — these are called CD4 T helper cells, or CD4 T cells.

Once the T cells are infected, they can’t do their part in helping protect the body from other diseases or infections. That’s why the illness that people get from HIV infection is called Acquired Immune Deficiency Syndrome, or AIDS.

Someone with full-blown AIDS would have almost no T cells, and they could die of any number of different infections or diseases that wouldn’t normally afflict someone with a healthy immune system.

“Today we have treatments that can stop HIV from replicating itself, and the T helper cells can come back,” said Hany Zakaria Meås, a postdoc at CEMIR and a co-first author of the article. “You can live a perfectly healthy life, but you have to take medicine your whole life, because the day you stop treating it, the virus will come back.”

The virus comes back if antiretroviral therapy is stopped because HIV hides its genetic material inside T cells that are dormant. That means there’s always the potential for more virus to appear and wreak havoc.

These reservoirs of virus have spurred a worldwide hunt for ways to shock, or kick the virus out of the cells where it lies dormant.

If the virus that lies dormant in cells could be smoked out into the open, the formally dormant virus could then be killed by the body’s immune system or drugs, and that would leave the patient HIV free, and cured, Meås said.

“We need to activate the virus so it can start replicating, and that will make the cell visible to the immune system,” he said. “That is the current idea for a cure. We just need to activate cells that are hiding away so we can kill them, while we give medicine that protects cells from infection, because there will be more virus produced.”

One such clinical trial in the UK, called the RIVER study, tried this approach but reported last year that the trial did not succeed, he said.

HIV comes in different varieties, and not all varieties are equally able to infect all T helper cells. To infect a cell, the virus has to have to have a specific ligand, which functions like a key, that has to match up on the target cell with the right kind of receptor, or keyhole.

When a T helper cell doesn’t have the receptor that matches the ligand on the HIV virus trying to infect the cell, that means the virus can’t actively infect that T cell. Instead, the virus can get trapped in a vesicle in the cell called an endosome.

The CEMIR researchers decided to look at what happened with uninfected T helper cells that had trapped HIV in endosomes. The uninfected cell responds to the HIV in the endosome by destroying the contents of the endosome, Meås said.

In the past, researchers have believed that this particular pathway — HIV being trapped in an endosome of a T helper cell, and the T helper cell destroying the contents of the endosome — was a kind of dead end for HIV infection. After all, the T helper cell hadn’t actually been infected, and the endosome destroyed the virus.

But now CEMIR researchers have found a previously undescribed immune response that results from HIV destruction in the endosome. This response may hold the key to allowing the shock-and-kill approach to work.

What the researchers found was when the endosome destroys the HIV, some of the genetic material is exposed to the T cell, which in turn activates a type of molecule called TLR8. This in turn results in the production of substances called cytokines, which cause inflammation in the body.

One reason this is surprising is that T cells are part of our immune system called the “adaptive” immune system, which responds to specific infectious substances over time.

Our immune system also has an “innate” part, which we are born with, and which provides more general immune protection by recognizing and responding to bits of viruses or bacteria that are common across many different viruses or bacteria.

TLR8 is a part of the body’s innate immune system. T cells are part of the adaptive immune system. Generally, it has been thought that these two systems were separate, independent branches.

“In this study we show that a receptor associated with the innate system actually exists and functions in the adaptive immune system,” Meås said.

The inflammation caused by the cytokines helps to wake up T cells that had formally been dormant and that contain HIV genetic material, said Markus Haug, a staff scientist at CEMIR and co-first author of the study.

“The T cell detects the virus and produces cytokines, and these cytokines act on cells that are properly infected with HIV and makes them produce more virus. The dormant T helper cells produce virus, and the T cells that were actively producing virus will produce more of it,” Haug said.

In other words, the TLR8 signal and cytokine-induced inflammation shock the HIV out of the dormant cells — where it can be destroyed.

The destruction of HIV by endosomes and the associated inflammation may also be one reason why patients who have been on antiretroviral treatments for decades are now beginning to develop inflammatory diseases more commonly associated with people decades older.

These include dementia, cardiovascular diseases, metabolic syndrome and cancers that aren’t related to HIV.

Meås said that the mechanism where endosomes destroy HIV might release enough genetic material to trigger the T cell’s innate immune receptors to cause inflammation.

Beyond that, however, the findings do offer hope, said Jan Kristian Damås, a chief attending physician at the Department of Infectious Diseases, St. Olav’s Hospital, Trondheim University Hospital and an NTNU professor associated with CEMIR. Damås works with HIV patients and recruited the nine patients whose cells were used as part of the research. He is also an author on the paper.

“Today we have very efficient drugs for suppressing HIV. However, we are not able to eradicate the virus and just weeks after patients stop medication the virus will reappear from virus reservoirs. Researchers and scientists believe that we can find a cure for HIV if we are able to eradicate these reservoirs,” Damås said.

“The breakthrough paper by Meås and Haug brings novel insight in mechanisms for reversal of HIV latency, and their findings of TLR8 as an important receptor for HIV in T cells, clearly represent a potential novel therapeutic target for treating HIV. Moreover, their findings may also represent major step forward in vaccine development as TLR8 ligands could be used as vaccine adjuvants that shape the type of T cell responses that is induced by the vaccine.”

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Short-term use of HIV-prevention medication protects at-risk men on vacation

Short-term use of pre-exposure prophylaxis (PrEP) medication could be a highly successful way to prevent the spread of HIV in men who have sex with men and have difficulty with long-term PrEP use. It may also work to transition men to long-term PrEP use, which has been shown to be highly effective in reducing HIV transmission.

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Even if Filipinos still can’t widely access pre-exposure prophylaxis (PrEP)…

Men at particular risk for HIV are very likely to consistently take prevention medication during vacations when their odds of contracting the virus are higher, according to a new study led by scientists at the University of Pittsburgh Graduate School of Public Health, The Fenway Institute and Harvard University.

The findings, published in the Journal of Acquired Immune Deficiency Syndromes, indicate that short-term use of pre-exposure prophylaxis (PrEP) medication could be a highly successful way to prevent the spread of HIV in men who have sex with men and have difficulty with long-term PrEP use. It may also work to transition men to long-term PrEP use, which has been shown to be highly effective in reducing HIV transmission.

“We started this as a feasibility study to see if we could identify barriers to short-term PrEP use and make adjustments. But we were excited when we got the results and discovered that almost all the participants were adherent to the point of protection against HIV,” said lead author James Egan, Ph.D., M.P.H., assistant professor of behavioral and community health sciences at Pitt Public Health. “This gives us a promising strategy to pursue in engaging at-risk men in HIV prevention efforts that work for them.”

When taken as a daily pill, PrEP reduces the risk of getting HIV from sex by about 99%, according to the Centers for Disease Control and Prevention. However, adhering to a daily medication regimen doesn’t work for everyone for reasons that include cost and individual concerns about the biological consequences of long-term medication.

Previous studies have shown that there are certain periods when men who have sex with men are more vulnerable to contracting HIV, including when traveling, on vacation, moving to a new city or after a break-up. Egan and his team set out to explore whether these men might be more receptive to adhering to PrEP treatment during these times.

The team followed 48 adult men from Pittsburgh or Boston who have sex with men in a pilot program to test the daily use of PrEP for 30 days that included an out-of-town vacation, with the men starting the medication seven days before the trip and continuing for at least seven days after vacation. The men were also given a brief session introducing them to the use of PrEP.

After their vacations, 94% of the men had blood concentrations protective against HIV, consistent with regular use of the medication. Almost 75% reported condomless sex during vacation, and about a third reported recreational drug use. None of the men contracted HIV during their vacation, though one of the men contracted the virus during the three-month post-vacation follow-up period when he’d had a lapse in use of PrEP associated with loss of health insurance and a move to a new city.

Additionally, 70% of the participants indicated an interest in continuing daily PrEP use long-term.

“That really stood out to us,” said senior author Kenneth Mayer, M.D., medical research director at The Fenway Institute at Fenway Health in Boston and professor of medicine at Harvard. “It shows us that introducing short-term use of PrEP before a vacation could lead to longer-term use. This presents an enticing opportunity to reduce HIV transmission.”

However, the scientists pointed out, the study included men who were motivated to enroll and did not address the likelihood of physicians prescribing PrEP for short-term use, the ease of obtaining PrEP for use only during vacations or the impact of the study’s brief counseling on the use of PrEP.

“These are all areas that our findings suggest warrant future explorations,” Egan said. “Our study tells us short-term adherence to PrEP during high-risk periods is tolerable in men who have sex with men, and that it could lead to long-term use. Now we need to determine how to make it possible in the real-world setting.”

Additional authors on this research are Ken Ho, M.D., M.P.H., and Ron Stall, Ph.D., M.P.H., of Pitt; Moe T. Drucker, B.S., and Ryan Tappin, N.P., M.P.H., of Fenway Health in Boston; Craig W. Hendrix, M.D., and Mark A. Marzinke, Ph.D., of Johns Hopkins University; Steven A. Safren, Ph.D., of Fenway Health and the University of Miami; Matthew J. Mimiaga, Sc.D., M.P.H., of Fenway Health and Brown University; Cristina Psaros, Ph.D., of Massachusetts General Hospital; and Steven Elsesser, M.D., of Fenway Health and the University of Pennsylvania.

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Health & Wellness

Notable percentage of trans men who have sex with men never got tested for HIV, bacterial and viral STIs

When considering screening for HIV and sexually transmitted infections (STIs), transgender men who have sex with men (TMSM) represent an understudied population. A study found that a notable percentage of TMSM had never tested for HIV and bacterial and viral STIs.

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When considering screening for HIV and sexually transmitted infections (STIs), transgender men who have sex with men (TMSM) represent an understudied population. A study found that a notable percentage of TMSM had never tested for HIV and bacterial and viral STIs.

In “Sociodemographic and behavioural factors associated with testing for HIV and STIs in a US nationwide sample of transgender men who have sex with men” – done by Nadav Antebi-Gruszka, Ali J. Talan, Sari L. Reisner and Jonathon Rendina, and published in BMJ Journals – researchers tried to examine HIV and STI testing prevalence among TMSM along with the factors associated with testing in a diverse sample of TMSM. They used data from a cross-sectional online convenience sample of 192 TMSM, analyzed using multivariable binary logistic regression models to examine the association between sociodemographic and behavioral factors and lifetime testing for HIV, bacterial STIs and viral STIs, as well as past year testing for HIV.

The researchers found that more than two-thirds of TMSM reported lifetime testing for HIV (71.4%), bacterial STIs (66.7%), and viral STIs (70.8%), and 60.9% had received HIV testing in the past year. Engaging in condomless anal sex with a casual partner whose HIV status is different or unknown and having fewer than two casual partners in the past six months were related to lower odds of lifetime HIV, bacterial STI, viral STI and past year HIV testing.

Being younger in age was related to lower probability of testing for HIV, bacterial STIs and viral STIs.

The domiciles of the TMSM also affected their health-seeking behaviors. In this study, those residing in the South of the US were less likely to be tested for HIV and viral STIs in their lifetime, and for HIV in the past year.

Finally, lower odds of lifetime testing for viral STIs was found among TMSM who reported no drug use in the past six months.

According to the researchers, these findings indicate that a notable percentage of TMSM had never tested for HIV and bacterial and viral STIs, though at rates only somewhat lower than among cisgender MSM despite similar patterns of risk behavior.

They recommend for “efforts to increase HIV/STI testing among TMSM, especially among those who engage in condomless anal sex.”

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People You Should Know

Living with HIV in Digos City

Meet Robin Charles O. Ramos, a person living with HIV in Digos City in Davao del Sur. There are numerous challenges there – e.g. they still have to go to Davao City for their laboratory tests, and get monthly supplies of life-saving ARVs. But they are starting to organize so PLHIVs can help each other.

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“We cannot deny the fact that there are people who will really discriminate us (people living with HIV),” said Robin Charles O. Ramos, who is based in Digos City in Davao del Sur in Mindanao, southern Philippines. “(But) think twice… before you discriminate because (everyone can be infected with) HIV.”

BI AWAKENING

Charles, 33, used to be only attracted to girls. But when he was nine years old, “I (was also) attracted to boys. I realized that I am attracted to both sexes.”

Charles’ family teased him for this. But he added that it’s not like they can prevent him from being bisexual; this “runs in the family,” he said, with other family members also LGBTQIA.

“It was somewhat difficult for me to come out,” he said. This is because he lives in a “relatively small community (where people know me).”

Digos, a 2nd class city and the capital of the province of Davao del Sur, has a population of only 169,393 people (in 2015).

But Charles eventually told others, realizing the relevance of being true/honest to oneself. “I know it (may not be easy) but… the community will (eventually) understand who and what we are.”

FINDING OUT ABOUT HIS HIV STATUS

On November 30, 2017, Charles found out he has HIV.

Prior to the diagnosis, he recalled having bad health – e.g. his cough wouldn’t go away, he had lymph nodes in his throat, he easily got tired/stressed out, and he had recurring fever. He self-medicated, “taking paracetamol” and antibiotics.

“I lost a lot of weight,” Charles recalled, “from 56 kilograms to 48 kilograms.”

At that point, his mother told him: “It’s time to rush to the hospital.”

The attending physician had Charles undergo more tests… including HIV antibody test.

The person who gave him the news about his HIV status was “actually a friend of mine.” In fact, he pre-empted the counselor from telling him the result; “I told her myself, ‘It’s positive, right?’.”

EVERYONE CAN BE INFECTED

Even before then, Charles actually worked in HIV advocacy.

So the person who gave him the news about his HIV status was “actually a friend of mine.” In fact, he pre-empted the counselor from telling him the result; “I told her myself, ‘It’s positive, right?’.”

That was also “mind conditioning” for him, he said. “I conditioned my mind that I’m positive already… it’s a way of acceptance of the matter.”

Right there and then, Charles opted to tell family members. And they had one question for him: Why him, considering he’s in HIV advocacy, and should know better?

“Anyone can be infected,” Charles said to them.

“Think twice… before you discriminate because (everyone be infected with) HIV.”

BEING OPEN ABOUT LIVING WITH HIV

If there’s one thing Charles said that’s good about being out, it’s being able to get external help as needed.

“I lose nothing by coming out,” he said. And for him, “PLHIVs need to come out… as a strategy for us to eradicate stigma and discrimination.”

At this stage in his life, “I don’t care if they talk about me. This is already here. Just accept it.”

Charles is also a teacher, and he opted to tell his supervisors and peers about his medical condition. This honesty paid off since “they support me.” His workmates always remind him to “not be stressed” and “have time to rest”.

HIV-RELATED ISSUES IN DAVAO DEL SUR

HIV screening and/or testing is, at least, accessible to the people of Digos City, said Charles. The social hygiene clinic (SHC) of the local government unit (LGU), for one, offers this; and “every time we conduct (gatherings) about HIV, there is HIV testing (given).”

It is the access to life-saving medicines (the antiretroviral treatment, or ARV) that is problematic.

“Here in Digos City, ARV is not yet available,” Charles said.

And so PLHIVs from there have to go to the Southern Philippines Medical Center (SPMC) in Davao City, which is 62.5 kilometers away (or approximately an hour of commute).

If there’s one thing Charles said that’s good about being out, it’s being able to get external help as needed.

Many of the PLHIVs from Digos City go to SPMC together, renting a van to take them to and from Davao City for their regular tests and ARV supplies.

A related issue: PLHIVs have to go every month because they are only given a month’s supply because of procurement issues. The usual practice is to give PLHIVs supply for three months. And – even if the Department of Health denies that there are issues concerning ARV supplies – at least the Digos City experience highlights the continuing difficulty with accessing life-saving medicines.

The dream for PLHIVs like Charles is for a refilling station to be established in Digos City to serve not only those living there, but also the nearby localities of Kidapawan City, Davao Occidental, et cetera.

EMPOWERING THE HIV COMMUNITY

Charles recognizes that many try to help PLHIVs, but he also thinks that empowering PLHIVs to help each other is essential.

“We have formally created a group: Bagani Southern Davao,” he said. The name was derived from the word “Bagani”, the peacekeeping force of the Manobo tribes and other indigenous groups in Mindanao. Akin to the word, “we’re warriors; we’re fighting against this illness.”

There are currently 20 active members; though, of course, not all PLHIVs in the area are members.

The dream for PLHIVs like Charles is for a refilling station to be established in Digos City to serve not only those living there, but also the nearby localities of Kidapawan City, Davao Occidental, et cetera.

To other PLHIVs in the area, Charles said he recognizes that it may take time before they can decide if they’d come out. “I respect (this) decision… But coming out as PLHIV is a way of educating people that they shouldn’t fear us, and that (having HIV) isn’t the end of our lives or the end of anything.”

As PLHIVs, he said, “we have more to offer, more to do” particularly in educating people.

And to non-PLHIVs or those who do not know their HIV status: “Know your status. Get tested. And stop discriminating people. It’s not like we wanted this to happen to us. But this is already here. We just need your support, and the respect that we want because we’re still human beings.”

“I lose nothing by coming out,” he said. And for him, “PLHIVs need to come out… as a strategy for us to eradicate stigma and discrimination.”

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HIV research over-emphasizing select populations at detriment of others – study

Medication to manage HIV is now very effective at keeping people well. But over half of people living with HIV do not take their medication as prescribed. The problem could be in the way that studies are designed in the first place – with BAME communities, women and straight men under-represented.

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People with HIV from Black, Asian and minority ethnic (BAME) communities, women and heterosexual men are underrepresented in HIV studies. This is according to research from the University of East Anglia and Western Sydney University.

Medication to manage HIV is now very effective at keeping people well. But over half of people living with HIV do not take their medication as prescribed. But the world has yet to find solutions that are routinely used by healthcare teams to successfully support people to take their medication as prescribed – despite many studies designed to investigate the problem.

New research revealed that the problem could be in the way that studies are designed in the first place – with BAME communities, women and straight men under-represented.

The research team said that this imbalance of representation needs to be fixed, in order to design solutions that suit the needs of a diverse population and keep people with HIV living longer, healthier lives.

Lead researcher Prof Debi Bhattacharya from UEA’s School of Pharmacy said: “It’s really important that people with HIV start taking medication as soon as possible and continue taking it as prescribed for life. While medication can’t cure HIV, taking it correctly helps people live longer, healthier lives. Medication can also reduce the risk of HIV transmission.”

The research team reviewed 80 studies designed to evaluate different approaches for supporting people to take their HIV medication correctly. They found that people from ethnic minorities, women and heterosexual men were underrepresented for the country in which the study was taking place.

Prof Bhattacharya said: “We found that none of the 80 studies had a trial population that reflected the actual population of people living with HIV. For example in many cases, gay men were over-represented in studies, compared with the amount of gay men living with HIV.”

In one American study, not a single woman was included even though women represent around one in five people with HIV.

“This is a problem because we know that in several countries including America, HIV rates in men are falling more than they are for women.”

As these patient groups are being significantly underrepresented in these types of trials, their needs, beliefs and attitudes to treatment are not fully understood. This potentially leaves these populations without the support they need to live well with HIV.

“We also know that language profoundly affects the way patients understand their treatment routines – which impacts on how they engage with their disease and medication. Failure to take this into account seriously hinders people from getting the best clinical outcomes.”

Research methods must be adapted to support the wide range of people with differing needs that make up the diversity of people with a specific disease.

The researchers similarly found that none of the studies used research methods to encourage people with differing languages and culture to contribute in the ways that are needed for the research to be successful.

“This may explain why we have seen few of these solutions that are shown to work in the studies then go on to be routinely used in healthcare.”

Over the years, greater scrutiny has been noted on how research is conducted to ensure that people invited to participate in research are fully informed before they decide to participate. “But, the changes have led to new problems, such as people with limited literacy or those less fluent in the local language being excluded from studies. It is important that we continue to protect the public whilst also supporting people with differing needs to participate in research.”

According to the researchers, the guidelines for carrying out research need to recognize that research methods must be adapted to support the wide range of people with differing needs that make up the diversity of people with a specific disease.

“The guidelines also need to communicate more strongly, the importance of properly involving people for whom the research is intended to help, at the earliest possible stage of the research otherwise these health inequalities may continue.”

This research was led by the University of East Anglia in collaboration with Western Sydney University, Australia.

‘Do interventions to improve adherence to antiretroviral therapy recognise diversity? A systematic review’ is published in the journal AIDS Care.

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Long-acting, injectable drug could strengthen efforts to prevent, treat HIV

Long-acting injectable formulations appear to be greatly preferred by both patients and physicians compared to current daily drug regimens that can be challenging to maintain. Additionally, the steady therapeutic drug levels provided by such a formulation would reduce the risk of drug resistance caused by missed daily pills, as well as reduce side effects.

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Scientists have developed an injectable drug that blocks HIV from entering cells. They say the new drug potentially offers long-lasting protection from the infection with fewer side effects. The drug, which was tested in non-human primates, could eventually replace or supplement components of combination drug “cocktail” therapies currently used to prevent or treat the virus.

University of Utah Health scientists led the study in collaboration with researchers from the National Institute of Allergy and Infectious Diseases (NIAID), Beth Israel Deaconess Medical Center in Boston, and Navigen, Inc.

“This is an exciting new HIV therapeutic option for both prevention and treatment, with a unique mechanism of action compared to other approved drugs,” says Michael S. Kay, M.D. Ph.D., a senior author of the study and a U of U Health professor of biochemistry. “It has great potential to help patients who suffer from drug resistance as well as those who would benefit from a longer-acting, injectable anti-HIV drug cocktail.”

The study appears in Proceedings of the National Academy of Sciences (PNAS).

In 2019, about 1.7 million people worldwide were newly infected with HIV, according to the World Health Organization. More than 38 million people are currently living with the infection. Combination antiretroviral therapy (cART), the so-called “drug cocktail,” has dramatically improved survival and quality of life for such patients, but it is also costly, often has serious side effects, and requires patients to take pills daily. In addition, because HIV frequently mutates, drug resistance is a constant challenge, Kay says, so researchers are always seeking new drugs with novel mechanisms of action to produce more robust combination therapies.

In this new study, the researchers tested a unique drug called CPT31, based on a D-peptide that targets a critical pocket on HIV’s fusion machinery that rarely mutates. D-peptides are mirror images of naturally occurring peptides. To imagine it, think of right and left hands. The building blocks and overall structure of natural peptides are analogous to our left hand versus our right hand for D-peptides.

Because of that, CPT31 and other D-peptides are not degraded in the body. Therefore, they last much longer than natural peptides, making them especially suitable for a long-acting injectable formulation.

“In addition to their durability in the body, D-peptides are largely ignored by the immune system, preventing immune reactions that are a side effect often seen with traditional peptide and protein drugs,” says Brett Welch, a co-author of the study and senior director of technology and strategy at Navigen, Inc., the Salt Lake City company that co-developed CPT31 and is managing clinical trials. “As a D-peptide, our hope is that CPT31 will provide extended viral suppression with a lower dose and reduced side effects.”

To see if CPT31 could prevent HIV infection, Kay and colleagues first injected the drug into healthy macaque monkeys starting several days prior to exposure to a hybrid simian-human form of HIV called SHIV. The monkeys were completely protected from this very high SHIV exposure, much higher than what humans typically encounter, and never developed signs of infection. Subsequently, the scientists identified the minimum dose of CPT31 needed to confer complete protection, information that will help inform clinical trials.

“We think this drug could be used by itself to prevent HIV infection because initial HIV exposure typically involves a relatively small amount of virus,” Kay says. “This study showed that the vast majority of circulating HIV strains from around the world are potently blocked by CPT31.”

But what about later stages of the disease when there are billions of copies of the virus circulating in the body?

To find out, the researchers gave CPT31 to monkeys with untreated SHIV infections and high viral loads. Over the course of 30 days, the drug significantly lowered the presence of SHIV in their bloodstreams. However, virus levels rebound in two to three weeks due to drug resistance, as typically observed when treating established infections with a single drug.

Finally, the researchers tested the drug’s ability to maintain viral suppression after a cART drug cocktail is discontinued in macaques. cART reduces SHIV to an undetectable level, but the virus rapidly rebounds after discontinuing therapy (as also seen in humans). In this study, CPT31 by itself effectively kept the virus at an undetectable level for months (until drug administration was discontinued).

“Such a simplified ‘maintenance therapy’ could present patients with a new option for viral control that is more cost-effective, convenient to take, and has fewer side effects,” Kay says.

In parallel with clinical trials, Navigen is developing a long-acting injectable formulation of CPT31 with the goal of only requiring injection of the drug once every three months.

“Long-acting injectable formulations appear to be greatly preferred by both patients and physicians compared to current daily drug regimens that can be challenging to maintain,” Welch says. “Additionally, the steady therapeutic drug levels provided by such a formulation would reduce the risk of drug resistance caused by missed daily pills, as well as reduce side effects.”

Upcoming human trials, scheduled for later this year, will help determine whether CPT31 is safe and effective in humans. Kay says that the full course of human clinical trials and subsequent FDA approval could take several years.

In addition to Dr. Kay, other U of U Health researchers involved in this study titled, “Prevention and Treatment of SHIVAD8 in Rhesus Macaques by a Potent D-peptide HIV Early Inhibitor,” were J.N. Francis and A.R. Smith. Additional researchers included Y. Nishimura, O. Donau, E. Jesteadt, R. Sadjadpour, and M.A. Martin of the National Institute of Allergy and Infectious Disease (NIAID); and M.S. Seaman of Beth Israel Deaconess Medical Center. The study was funded by the National Institutes of Health (NIAID) and the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery. Drs. Kay and Welch hold equity in Navigen.

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Study finds benefit in more frequent HIV screenings for young men who have sex with men

HIV screening every three months, in addition to existing patterns of HIV screening among YMSM, would most improve HIV transmission and life expectancy among these men while remaining cost-effective. However, the results do not apply to youth who do not meet high-risk criteria.

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A study has found that HIV screening every three months compared to annually will improve clinical outcomes and be cost-effective among high-risk young men who have sex with men (YMSM). The report, led by researchers at the Massachusetts General Hospital (MGH), is published in Clinical Infectious Diseases.

Young men who have sex with men account for the biggest chunk of those who get infected with HIV every year.

In the Philippines, for instance, data from the Department of Health in 2019 showed that from October to December 2019, 926 (31%) cases were among youth 15-24 years old and 94% were male. Almost all were infected through sexual contact (89 male-female sex, 597 male-male sex, 233 sex with both males and females).

In the US, one in five new HIV infections is YMSM, and “yet more than half of young men who have sex with men and who are living with HIV don’t even know that they have it,” says Anne Neilan, MD, MPH, investigator in the MGH Division of Infectious Diseases and the Medical Practice Evaluation Center, who led the study. “With so many youth with HIV being unaware of their status, this is an area where there are opportunities not only to improve care for individual youth but also to curb the HIV epidemic…”

Despite these numbers, the Centers for Disease Control and Prevention previously determined that there was insufficient youth-specific evidence to warrant changing their 2006 recommendation of an annual HIV screening among men who have sex with men (MSM).

HIV screening refers to testing of individuals who do not have symptoms of the infection. As defined by the study, high-risk refers to a recent history of condomless anal intercourse, sexually transmitted infection, or multiple sexual partners. Given the disproportionate impact of the HIV epidemic on YMSM, screening for HIV more frequently than current recommendations could identify infections that would otherwise be missed.

HIV screening every three months, in addition to existing patterns of HIV screening among YMSM, would most improve HIV transmission and life expectancy among these men while remaining cost-effective. However, the results do not apply to youth who do not meet high-risk criteria.

The study used data from the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) on how often HIV occurs in each age group, as well as the stage of disease at the time of diagnosis, to project the probable results of screening every three months, six months, or yearly.

Because a traditional study design to examine how often young men who have sex with men should be screened would be nearly impossible to conduct, the authors used a well-published computer microsimulation model developed by members of the research team.

The analysis revealed that HIV screening every three months, in addition to existing patterns of HIV screening among YMSM, would most improve HIV transmission and life expectancy among these men while remaining cost-effective. However, the results do not apply to youth who do not meet high-risk criteria.

Andrea Ciaranello, MD, MPH, investigator MGH Division of Infectious Disease, senior author of the study, says: “The improvements in life expectancy and reduction in HIV transmission were substantial. With more frequent screening, we also estimated that there would be additional, important improvements in the proportion of YMSM who are able to engage in HIV treatment and have excellent control of their HIV infection.”

The authors also highlighted the opportunities for improved implementation of current annual screening recommendations. “If even the current CDC recommendations for annual HIV screening among YMSM could be fully met, important gains could be made both for the health of youth with HIV and in working toward our goal of ending the HIV epidemic,” says Ciaranello. “Ultimately, our study underscores the value of ongoing research to examine the most effective ways to increase HIV screening among youth.”

Neilan adds: “We found that screening every three months was cost-effective.”

In the US, the screening program itself cost up to $760 per person screened. The test itself cost $38-76;.

“This suggests that a large additional investment in innovative HIV screening approaches for youth, including venue-based screening or mobile screening units, would be of good value,” Neilan ends.

Neilan is also an Instructor in Medicine, and Ciaranello is an associate pdrofessor of Medicine at Harvard Medical School.

Additional co-authors of the report are Alexander J. B. Bulteel, Julia H. A. Foote, Kenneth A. Freedberg, MD, MSc, Rochelle P. Walensky, MD, MPH, Pooyan Kazemian, PhD, MGH Medical Practice Evaluation Center; Sybil G. Hosek, PhD, Stroger Hospital of Cook County; Raphael J. Landovitz, MD, MSc, University of California, Los Angeles; Stephen C. Resch, PhD, MPH, Milton C. Weinstein, PhD, Department of Health Policy and Management, Harvard T. H. Chan School of Public Health; A. David Paltiel, PhD, MBA, Yale School of Public Health; and Craig M. Wilson, MD, Department of Epidemiology, University of Alabama at Birmingham School of Public Health.

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