Tag: HIV treatment

Categories : HIVTags :

Opinion: HIV Investments Remain No-brainers, but Some Things Need to Change

On By ModernMedia
Photo by Miguel Á. Padriñán

By Marcus Louw for Spotlight

Making the case for governments and donors to pump money into the HIV response has become more difficult over the last decade. This is partly a result of the notable successes we’ve had – for example, in 2022, HIV-related deaths in South Africa were down to less than a fifth of what it was in 2005. There is clearly some justification for the point of view that HIV simply isn’t the crisis it used to be.

That said, it is also true that about 8 million people in South Africa are living with HIV. This number will continue to rise in the coming years as the rate of new HIV infections is much higher than the rate of HIV-related deaths. Barring a major scientific breakthrough, all these millions of people will require antiretroviral medicines for the rest of their lives, both for their own health and to reduce onward transmission of the virus. In this context, a failure to maintain and improve HIV treatment and prevention programmes will have catastrophic consequences.

There is also increasing competition with other areas of urgent need. In recent years, climate change and COVID-19 have understandably made the headlines much more frequently than HIV. There is also a slow shift underway in South Africa’s disease burden, away from HIV and tuberculosis toward non-communicable diseases (NCDs) such as diabetes and hypertension.

Still a no-brainer

Despite these shifts, there is good reason to think that spending money on HIV continues to offer excellent value for money. For example, according to a recent report by Economist Impact (part of the Economist group that also publishes the Economist magazine), for every dollar spent on HIV in South Africa from 2022 to 2030, it is estimated the country will see GDP gains of over $7.

We also have a good idea of the impact and cost-effectiveness of specific HIV-related interventions. According to the most recent version of the South Africa HIV investment case, published in December 2021, condom provision continues to be the most cost-effective intervention in South Africa, followed by antiretroviral treatment, infant testing, pre-exposure prophylaxis for men who have sex with men, and general population testing. Voluntary medical male circumcision has become less cost-effective as coverage levels have risen in recent years, but remains worth it. In fact, the investment case leaves no doubt that most of the key interventions needed to combat HIV in South Africa are both worth it and affordable.

Despite all this, according to a recent UNAIDS report, global investment in HIV has taken a knock in recent years, and in 2022 we were essentially back down to the same level as in 2013. Such reductions constitute a crisis in HIV funding, especially in poor countries that are heavily reliant on donor funds. In South Africa, key interventions like antiretroviral treatment and condoms generally remain funded, but public sector health budgets have been shrinking in real terms, something that is no doubt impacting the HIV programme.

Time to leverage HIV investments

This brings us back to the knotty problem with which we started – while HIV remains a large and serious problem and most investments in combatting HIV remain excellent value for money, making the case for these investments has become more difficult due to competing priorities and the fact that, in South Africa at least, people are not dying of AIDS at nearly the rate they did 20 years ago. How to best make the case in a way that convinces governments and donors to put up the money in this context is a devilishly hard problem.

There are certainly no simple solutions.

What there is, though, is some indications that a too narrow focus on HIV is becoming a harder sell. There is also a risk that as funds for HIV get harder to come by, and the clamour for funding NCDs becomes more pronounced, we may end up pitting diseases against each other in a way that benefits no one.

Given the incredible acuteness of our HIV crisis ten and 20 years ago, a laser focus on HIV was right and necessary. Today, however, the reality is that many people living with HIV are also living with NCDs like diabetes or hypertension, something that will become only more so as the population of people living with HIV grow older. It is clear that we need to start doing a better job of integrating care and treatment for all the different diseases one person might have – the key is to do so in a way that doesn’t drop the ball when it comes to HIV.

In some areas progress is already clear – medicines distribution via pickup points closer to people’s homes were fuelled by the need to get ARVs to people, but is now also being used to distribute medicines for some NCDs. In other areas, such as data systems, integration however remains limited and the systems available for HIV and TB remain superior to those for NCDs.

There appears to be a broader policy shift along these lines. As recently reported on Devex, the Global Fund to Fight HIV, TB, and Malaria’s current five-year strategy explicitly endorses and promises funding for integrating non-communicable disease services with TB and HIV programmes. UNAIDS’s new ‘The path to end AIDS’ report also makes the right noises on the “deeper integration of HIV and other health services”, as does South Africa’s National Strategic Plan for HIV, TB, and STIs 2023 – 2028.

Of course, the road from policy-level ambitions such as these and change on the ground can be a long one – to some extent such integration has been on the cards for over a decade. But, rising NCD rates, an ageing population of people living with HIV and comorbidities, and funding pressures mean that getting integration right is now more urgent than ever.

One of the arguments for HIV-specific funding has always been that HIV investments have benefited healthcare systems more generally, even if that was not the primary intention. Maybe in this next act of the HIV response then, the key will be to stop thinking of health system improvement as a side effect of HIV investments and instead lean into the idea of explicitly leveraging what we’ve done and will continue to do in HIV to improve health systems more generally.

Republished from Spotlight under a Creative Commons Licence.

Source: Spotlight

Categories : HIV PaediatricsTags :

SA AIDS 2023: New Treatments and Guidelines to Benefit Kids, with More Advances on The Horizon

On By ModernMedia
Photo by Sergey Mikheev on Unsplash

By Elri Voigt for Spotlight

Several sessions at the 11th SA AIDS conference, recently held in Durban, highlighted the worrying fact that key HIV numbers such as treatment coverage are much lower in children than in adults. There is hope, however, that new treatments and new treatment guidelines might help close the gap.

In a plenary session, Dr Sandile Buthelezi, Director General of the National Department of Health, told delegates that on UNAIDS’ 95-95-95 targets, children in South Africa are at 81-65-68. This means that 81% of children living with HIV have been diagnosed, 65% of those diagnosed are on antiretroviral treatment, and 68% of those on treatment are virally suppressed. For the South African population as a whole, the numbers are at 94-76-92.

Throughout the conference, various speakers highlighted the fact that only 65% of children who have been diagnosed are on treatment as a particular concern. To close the gap and reach UNAIDS’ target of 95%, just over an additional 88 000 children would need to be initiated on treatment.

Professor Lee Fairlie, Director of Maternal and Child Health at Wits RHI, said in a presentation that only 52% of children younger than 14 living with HIV are on treatment. Fairlie also pointed out that children lagged behind substantially when it comes to viral suppression, and this is particularly challenging in the youngest age groups.

Not all bad news

But it was not all bad news at this year’s conference. One piece of good news is that new and better child-friendly antiretroviral formulations are being rolled out in South Africa. These new treatments should make it easier for children to start and stay on treatment – children often find it difficult to take medicines formulated for adults, due to factors like incorrect dosing, large pills, and bad taste.

The National Department of Health recently updated the country’s antiretroviral treatment guidelines to allow for the use of several of these new formulations and better HIV treatment regimens for children. Most notable is the introduction of a new regimen consisting of the medicines abacavir, lamivudine and dolutegravir (ALD for short).

Speaking at the conference, Dr Leon Levin, a paediatrician who has been treating infants, children, and adolescents living with HIV for almost three decades, pointed out that the availability of new paediatric formulations had a major impact on the new treatment guidelines. (Spotlight previously reported on the registration of some of these new formulations here.) Levin is also the Senior Technical Advisor in Paediatrics at the NGO Right to Care.

One such child-friendly formulation is a 120/60mg scored, dispersible tablet of abacavir and lamivudine that can be taken in patients who weigh between 3 and 25kg. It is given once daily and two generics are registered with the South African Regulatory Authority (SAHPRA). “It’s going to literally replace all the other paediatric Abacavir+3TC formulations. You can swallow it, chew it, crush it, or dissolve it in water. So [it’s] very versatile,” he said.

Also important is a paediatric formulation of the antiretroviral dolutegravir – a medicine that forms the backbone of HIV treatment in adults. According to Levin, the child-friendly version of dolutegravir is not available to everyone yet, and many clinicians still need to undergo training on how to use it. It is a 10mg dispersible, scored tablet given once daily that can be used at 3kg and higher and from four weeks of age onward. There are two generic versions of this product registered with SAHPRA.

The introduction of paediatric dolutegravir is likely to overshadow the introduction of a four-in-one formulation of abacavir, lamivudine, lopinavir/ritonavir. The four-in-one combination has to be taken twice daily, is strawberry flavoured and comes in a powder form. “Unfortunately, this product to nobody’s fault was launched at the same time as paediatric dolutegravir. Which means paediatric dolutegravir is going to take centre stage and this product unfortunately is not going to be used much,” Levin said.

Updated guidelines

Levin explained that the changes to South Africa’s treatment guidelines focused on doing two main things when it comes to children living with HIV, the first is to implement an optimised regimen – the ALD regimen and the second is to create an “enabling environment to support engagement in care and adherence”. He said that with the new guidelines, we can expect “much improved [viral] suppression, optimised regimens, improved synchronisation of clinic visits, happier patients and their families and clinicians as well”.

A big change to the guidelines is that now children who weigh 3kg and are four weeks of age should be started on the ALD regimen, instead of the abacavir, lamivudine, and lopinavir/ritonavir regimen that was previously recommended. “This is a major change. It’s a fantastic, well-tolerated regimen. It’s potent and you’re going to get around a lot of the issues you had with these younger children,” Levin said.

Once the children on this regimen get to 30kg, they will be switched to a regimen containing tenofovir, dolutegravir, and lamivudine (TLD for short). TLD is also the regimen adults living with HIV in South Africa are offered when starting treatment for the first time.

For children who are already on treatment, the new guidelines recommend that all children who are four weeks of age and older and weigh 3kg or more should be transitioned to a dolutegravir-containing regimen. For children with suppressed viral loads, the switch to ALD or TLD is straightforward, while for children without viral suppression, it can get more complicated.

Another important change is that children over five years of age are now eligible for Repeat Prescription Collection Strategies (RPCs) if they are virally suppressed and had an age-appropriate disclosure, which means that their HIV status has been explained to them in a way that is appropriate for their age, as outlined in the guidelines. For children under five, they can be given a three months supply at a time, providing they are at least six months old. Levin pointed out that whenever RCPs or a three months supply is considered for children, it is essential to look at where and how the parents may be receiving their own antiretroviral treatment so that it can be co-ordinated, and parents don’t have to go to two different places to collect the medications.

New options in the pipeline

While the paediatric formulations included in the new guidelines are a step forward, there are experimental treatments in the pipeline that may make treatment yet more convenient for children.

“There’s a rich pipeline of new combinations and drug delivery developments. Hopefully, this will further improve access, clinical and virological outcomes,” Fairlie said in a conference presentation. “Obviously, the paediatric market is extremely small and then one has to maintain enthusiasm for manufacturers to actually continue to look at the paediatric population. And so, merging of treatments and prophylaxis regimens is really what would work going forwards.”

In her presentation, she specifically referred to long-acting formulations of cabotegravir (CAB-LA) and rilpivirine (RPV). CAB-LA has already been approved by SAHPRA for HIV prevention in adults and, as Spotlight reported last week, pilot projects evaluating how to best provide the CAB-LA injection in South Africa are set to start soon. The combination of CAB-LA and rilpivirine injections has been approved for the treatment of HIV in adults by the United States Food and Drug Administration, but not yet by SAHPRA. The injections are administered every two months.

Fairlie says that currently there are several studies either ongoing or set to start soon for the use of these agents in the paediatric and adolescent age groups. In addition, there are also trials planned to test another long-acting medication called lenacapavir in adolescents and broadly neutralising antibodies (bNAbs) in children.

She also highlighted several improved delivery methods that are in the pipeline for paediatrics. These include a mechanism that doesn’t require water, like oro-dispersible tablets, also known as fast melts, which disintegrate in the mouth as well as oral films that stick to the mouth, disintegrate there, and dissolve. There are also various tablet options that are small enough for children to swallow easily. Like multi-particulates, which are small and solid, multiple-unit dosages that can take the form of granules, pellets, or beads. Mini-tablets are also a prospect – these are compressed tablets no larger than 4ml. Finally, there are novel mechanisms like long-acting oral drug delivery systems and micro-array patches. Fairlie explained that long-acting oral drugs are where a drug is stored in the centre of a capsule that has a number of “arms”, which are able to keep the capsule in the stomach and slowly dissolve and release the drug into the stomach. This allows for slow-release dosing. The “arms” tend to break down after about seven days.

Republished from Spotlight under a Creative Commons Licence.

Source: Spotlight

Categories : Gender HIVTags :

OPINION: With the Right Interventions We can Help Many More Men Start and Stay on HIV Treatment

On By ModernMedia

By Shawn Malone for Spotlight

June is Men’s Health Month and while the focus is mostly on men’s attitudes about their health, it is also worth reflecting on the health sector’s attitudes toward men.

We hear many stereotypes about men and health, but how many of those are actually true?

A few years ago representatives of The Mpilo Project spoke to more than 2 000 men in KwaZulu-Natal and Mpumalanga to understand why many find it hard to engage with HIV testing and treatment. We uncovered several myths and misperceptions in the process.

One common myth is that men are stubborn and apathetic about HIV – that they aren’t listening and don’t care. While many men may indeed wear a mask of indifference, HIV leaves many of them feeling paralysed by fear and anxiety. This is why we need a health service delivery approach rooted in encouragement and reassurance, not scolding and pressure.

Another common misconception is that men are mainly just workers who need practical solutions like convenient clinic hours and quick service. The reality is that men are complex human beings who face social and emotional barriers as well as practical ones. We need solutions that address both practical and psychosocial barriers.

There is also a view that sources of support are available and that men just fail to access them, perhaps because “they don’t really want support”. In fact, many men are hungry for support but see no sources that feel safe or relatable. They experience counselling as scripted, one-directional, overly technical, and often judgmental. The key is to give men the right sources of support and to speak empathetically to their individual issues and concerns.

Finally, there is a view that healthcare providers are helping men by taking proactive approaches like provider-initiated testing and tracking-tracing. But these often leave men feeling hunted and ambushed by the health system. We need proactive approaches that leave men feeling like they still have control over their own lives and decisions and help them develop their own internal motivation to start and stay on treatment.

These and other misconceptions can lead healthcare providers to conclude that men are simply difficult if not impossible to reach. But once we understand their barriers, that picture changes dramatically.

The 11th SA AIDS Conference concluded last week and in one of the plenary sessions we had the opportunity to respond to the question: “Strategies for reaching men—are we seeing a return on investment?”

The short answer is yes!

Since 2017, the percentage of men with HIV in South Africa who know their status has increased from 78% to 94%, nearly on par with women. We can attribute that in part to approaches like HIV self-testing that have made it quick, easy, and private for men to learn their status.

We’ve also seen good progress on viral suppression, which has increased from 82% to 93%, again comparable to the rate among women – proof that men on treatment are fully capable of being adherent.

Yet only 70% of men who know they have HIV are currently on treatment – hardly any increase at all from 68% in 2017.

Given the progress we’ve seen in men testing for HIV and achieving viral suppression, the persistent gap in men on treatment suggests that something is wrong – not with men but with the HIV treatment services and support we are offering them.

The good news

The good news is that we know much more than we did a few years ago about what works. Here are three examples.

The MINA campaign aims to reach men with “the new HIV story” by featuring stories from real men living a healthy, happy life with HIV on social media, television, radio, billboards, etc. The campaign also helps men feel more welcome in the clinic, using signage and materials to send the signal to men that “this is your space too”. MINA-supported districts and facilities have seen strong growth in testing and linkage, as well as modest improvement in retention in care.

The Coach Mpilo model employs men who are thriving with HIV as coaches of men at risk of non-initiation or disengagement. Coaches provide a safe, relatable source of support and serve as living proof that HIV is not the end of the road. Piloted in 2020 and currently implemented in 18 districts, the model is achieving 97% linkage to care and 94% retention.

The B-OK bead bottles are a simple visual tool for helping people to understand the benefits of HIV treatment and viral suppression and, more importantly, to build the motivation to start and stay on treatment. Red beads are HIV; black beads are healthy cells. A mixed bottle represents most people upon diagnosis. A red bottle represents the virus multiplying uncontrolled in the absence of treatment. A black bottle with one red bead represents viral suppression achieved through treatment adherence. In an evaluation of the tool, understanding of how HIV treatment works increased from 12.5% to 92.5%.

Men are not indifferent about their health and they are not inherently poor health-seekers. If many of them are avoiding healthcare services, let’s consider that it may be because they are not getting what they need from these services.

We have seen that men do engage when we in the public health sector meet them where they are rather than where we want them to be; when we speak to their needs and priorities rather than ours; when we give them the right sources of support rather than one-size-fits-all, and when we help them build understanding and motivation rather than simply instructing.

When we invest, we see returns. Let’s keep investing in scaling what works.

*Malone is the Project Director of The Mpilo Project, PSI.

Reproduced from Spotlight under a Creative Commons 4.0 Licence.

Source: Spotlight

Categories : HIVTags :

New Southern African HIV Guidelines Released Online

On By ModernMedia
Photo by National Cancer Institute on Unsplash

The Southern African HIV Clinicians Society has just released their updated 2023 guidelines for Antiretroviral Therapy in Adults. These updates reflect the changing treatment paradigms of the current era, specifically the consolidation towards dolutegravir- and darunavir-based treatment regimens, rather than efavirenz- or lopinavir-ritonavir based ones.

They are optimised for accessibility and are available in a PDF format for download, or are viewable as an online version directly on the website. The online version is in an easily navigable form, with the menu guiding readers to the different modules.

The new guidelines also incorporate numerous other changes to ensure that they stay up-to-date and helpful to the healthcare workers who use them. Some of the key changes include:

• Recommendation to shift most patients to a dolutegravir-based regimen if possible.

• For patients requiring a protease inhibitor (PI), recommendation for darunavir as the PI of choice, and for lopinavir/ritonavir to only be considered where a PI is required to be co-administered with rifampicin-based tuberculosis treatment.

• New recommendations on the move away from routine use of zidovudine (AZT) in second-line therapy in favour of recycling tenofovir or, inpatients with renal dysfunction, abacavir.

• Advice on how to assess the increase in serum creatinine seen with dolutegravir/tenofovir fixed dose therapy.

• Guidance on the role of tenofovir alafenamide; TAF.

• Inclusion of enhanced baseline screening for tuberculosis and sexually transmitted infections.

• Expansion of the module on HIV and mental health.

While many antiretroviral therapy (ART) guidelines are available internationally, the current guidelines have been written to address issues relevant to Southern Africa. Only treatment and diagnostic options available in Southern Africa are included. These guidelines also consider affordability because of the region’s low- and middle-income countries. The guideline authors also recognise and addressed the need to bridge the gap in treatment recommendations between public and private sector programmes, as many patients transition between the two sectors for treatment.

Categories : HIVTags :

Scientists Advance Towards a Universal HIV Cure

On By ModernMedia
Photo by Sergey Mikheev on Unsplash

New research from Oregon Health & Science University is helping explain why at least five people have become HIV-free after receiving a stem cell transplant. The study’s insights may bring scientists closer to developing what they hope will become a widespread cure for HIV, hopefully without the need for costly techniques like stem cell therapy.

Published today in the journal Immunity, the OHSU-led study describes how two nonhuman primates were cured of the monkey form of HIV after receiving a stem cell transplant. It also reveals that two circumstances must co-exist for a cure to occur and documents the order in which HIV is cleared from the body – details that can inform efforts to make this cure applicable to more people.

“Five patients have already demonstrated that HIV can be cured,” said the study’s lead researcher, Jonah Sacha, PhD, OHSU professor.

“This study is helping us home in on the mechanisms involved in making that cure happen,” Sacha continued. “We hope our discoveries will help to make this cure work for anyone, and ideally through a single injection instead of a stem cell transplant.”

The first known case of HIV being cured through a stem cell transplant was reported in 2009. A man who was living with HIV was also diagnosed with acute myeloid leukemia, a type of cancer, and underwent a stem cell transplant in Berlin, Germany. Stem cell transplants, which are also called bone marrow transplants, are used to treat some forms of cancer. Known as the Berlin patient, he received donated stem cells from someone with a mutated CCR5 gene, which normally codes for a receptor on the surface of white blood cells that HIV uses to infect new cells. A CCR5 mutation makes it difficult for the virus to infect cells, and can make people resistant to HIV. Since the Berlin patient, four more people have been similarly cured.

This study was conducted with a species of nonhuman primate known as Mauritian cynomolgus macaques, which the research team previously demonstrated can successfully receive stem cell transplants. While all of the study’s eight subjects had HIV, four of them underwent a transplant with stem cells from HIV-negative donors, and the other half served as the study’s controls and went without transplants.

Of the four that received transplants, two were cured of HIV after successfully being treated for graft-versus-host disease, which is commonly associated with stem cell transplants.

Other researchers have tried to cure nonhuman primates of HIV using similar methods, but this study marks the first time that HIV-cured research animals have survived long term. Both remain alive and HIV-free today, about four years after transplantation. Sacha attributes their survival to exceptional care from Oregon National Primate Research Center veterinarians and the support of two study coauthors, OHSU clinicians who care for people who undergo stem cell transplants: Richard T. Maziarz, M.D., and Gabrielle Meyers, M.D.

“These results highlight the power of linking human clinical studies with pre-clinical macaque experiments to answer questions that would be almost impossible to do otherwise, as well as demonstrate a path forward to curing human disease,” said Maziarz, a professor of medicine in the OHSU School of Medicine and medical director of the adult blood and marrow stem cell transplant and cellular therapy programs in the OHSU Knight Cancer Institute.

The how behind the cure

Although Sacha said it was gratifying to confirm stem cell transplantation cured the nonhuman primates, he and his fellow scientists also wanted to understand how it worked. While evaluating samples from the subjects, the scientists determined there were two different, but equally important, ways they beat HIV.

First, the transplanted donor stem cells helped kill the recipients’ HIV-infected cells by recognizing them as foreign invaders and attacking them, similar to the process of graft-versus-leukaemia that can cure people of cancer.

Second, in the two subjects that were not cured, the virus managed to jump into the transplanted donor cells. A subsequent experiment verified that HIV was able to infect the donor cells while they were attacking HIV. This led the researchers to determine that stopping HIV from using the CCR5 receptor to infect donor cells is also needed for a cure to occur.

The researchers also discovered that HIV was cleared from the subjects’ bodies in a series of steps. First, the scientists saw that HIV was no longer detectable in blood circulating in their arms and legs. Next, they couldn’t find HIV in lymph nodes, or lumps of immune tissue that contain white blood cells and fight infection. Lymph nodes in the limbs were the first to be HIV-free, followed by lymph nodes in the abdomen.

The step-wise fashion by which the scientists observed HIV being cleared could help physicians as they evaluate the effectiveness of potential HIV cures. For example, clinicians could focus on analysing blood collected from both peripheral veins and lymph nodes. This knowledge may also help explain why some patients who have received transplants initially have appeared to be cured, but HIV was later detected. Sacha hypothesises that those patients may have had a small reservoir of HIV in their abdominal lymph nodes that enabled the virus to persist and spread again throughout the body.

Sacha and colleagues continue to study the two nonhuman primates cured of HIV. Next, they plan to dig deeper into their immune responses, including identifying all of the specific immune cells involved and which specific cells or molecules were targeted by the immune system.

Source: Oregon Health & Science University

Categories : Genetics HIVTags :

Curing HIV with a Dual Gene Editing Approach

On By ModernMedia
Source: Pixabay CC0

Gene editing therapy aimed at two targets – HIV-1 and CCR5, the co-receptor that helps the virus get into cells – can effectively eliminate HIV infection, report scientists in PNAS. This is the first to combine a dual gene-editing strategy with antiretroviral drugs to cure animals of HIV-1.

“The idea to bring together the excision of HIV-1 DNA with inactivation of CCR5 using gene-editing technology builds on observations from reported cures in human HIV patients,” said Kamel Khalili, PhD, professor at the Lewis Katz School of Medicine. “In the few instances of HIV cures in humans, the patients underwent bone marrow transplantation for leukaemia, and the donor cells that were used carried inactivating CCR5 mutations.”

Dr Khalili and Howard E. Gendelman, MD, professor at UNMC, were senior investigators on the new study from the Lewis Katz School of Medicine at Temple University and the University of Nebraska Medical Center (UNMC). The two researchers have been long-time collaborators and have strategically combined their research strengths to find a cure for HIV.

“We are true partners, and what we achieved here is really spectacular,” Dr Gendelman said. “Dr Khalili’s team generated the essential gene-editing constructs, and we then applied those constructs in our LASER-ART mouse model at Nebraska, figuring out when to administer gene-editing therapy and carrying out analyses to maximise HIV-1 excision, CCR5 inactivation, and suppression of viral growth.”

In previous work, Drs Khalili and Gendelman and their respective teams showed that HIV can be edited out from the genomes of live, humanised HIV-infected mice, leading to a cure in some animals. For that research, CRISPR gene-editing technology for targeting HIV-1 was combined with a therapeutic strategy known as long-acting slow-effective release (LASER) antiretroviral therapy (ART). LASER ART holds HIV replication at low levels for long periods of time, decreasing the frequency of ART administration.

Despite being able to eliminate HIV in LASER-ART mice, the researchers found that HIV could eventually re-emerge from tissue reservoirs and cause rebound infection. This effect is similar to rebound infection in human patients who have been taking ART but suddenly stop or experience a disruption in treatment. HIV integrates its DNA into the genome of host cells, it can lie dormant in tissue reservoirs for long periods of time, out of reach of antiretroviral drugs. As a consequence, when ART is stopped, HIV replication renews, giving rise to AIDS.

To prevent rebound infection, Dr Khalili and colleagues began work on next-generation CRISPR technology for HIV excision, developing a new, dual system aimed at permanently eliminating HIV from the animal model. “From success stories of human HIV patients who have undergone bone marrow transplantation for leukaemia and been cured of HIV, our hypothesis was that the loss of the virus’s receptor, CCR5, is important to permanently eliminating HIV infection,” he explained. They developed a simple and more practical procedure for the inactivation of CCR5 that includes an IV inoculation of the CRISPR gene editing molecule.

Experiments in humanized LASER-ART mice carried out by Dr Gendelman’s team showed that the constructs developed at Temple, when administered together, resulted in viral suppression, restoration of human T-cells, and elimination of replicating HIV-1 in 58% of infected animals. The findings support the idea that CCR5 has a key role in facilitating HIV infection.

The Temple team also anticipates soon testing the dual gene-editing strategy in non-human primates.

The new dual CRISPR gene-editing strategy holds exceptional promise for treating HIV in humans. “It is a simple and relatively inexpensive approach,” Dr Khalili noted. “The type of bone marrow transplant that has brought about cures in humans is reserved for patients who also have leukaemia. It requires multiple rounds of radiation and is not applicable in resource-limited regions, where HIV infection tends to be most common.”

Source: Temple University Health System

Categories : HIVTags :

Earlier HIV Diagnosis and Treatment Improves Outcomes

On By ModernMedia
HIV themed candle
Image by Sergey Mikheev on Unsplash

Compared to delaying antiretroviral treatment (ART) early in the course of HIV infection, an earlier start to ART when the immune system is stronger results in better long-term health outcomes, according to findings presented at the IDWeek Conference.

The findings are based on an extended follow-up of participants in the National Institutes of Health-funded Strategic Timing of Antiretroviral Treatment (START) study. In 2015, START demonstrated a 57% reduced risk of AIDS and serious non-AIDS health outcomes among participants who began ART when their CD4+ T-cell counts were greater than 500 cells/mm³ compared with those who did not begin ART until either their CD4+ counts fell below 350 cells/mm³ or they developed AIDS. Following the 2015 report of these findings, the participants in the deferred treatment arm were advised to begin ART.

The international START study proved the benefit of early ART initiation, but longer-term follow-up of 4446 participants was undertaken to determine whether the health benefits of early ART compared with deferred ART increased, remained constant, or declined after the participants in the deferred arm were advised to begin ART. The primary study endpoints included the number of participants who developed AIDS; those who developed serious non-AIDS health conditions, such as major cardiovascular disease, kidney failure, liver disease and cancer; and those who died.

For participants who began ART before the end of 2015, the median CD4+ cell count at the time of ART initiation was 648 cells/mm³ for the immediate arm and 460 cells/mm³ for the deferred arm. The analysis presented today compared the primary study endpoints before the end of 2015, with those in the extended follow-up period, from 2016–2021. In the latter period, most deferred-arm participants were taking ART. During the second period, people initiating ART in the deferred group had rapid and sustained declines in HIV viral load (less than or equal to 200 copies/mL); however, CD4+ cell counts remained, on average, 155 cells lower compared with that of individuals in the immediate ART group.

While the risk of serious health outcomes was substantially diminished soon after ART was initiated in the deferred treatment group, some excess risk remained compared with the immediate treatment group. The deferred ART group continued to have a somewhat greater risk (21%) of serious health consequences or death in comparison to the immediate treatment group. Over the five-year follow-up, there were 27 cases of AIDS in the deferred group compared with 15 cases in the early group. Similarly, 88 cases of serious non-AIDS health issues occurred in the deferred treatment arm compared with 76 cases in the immediate treatment arm. Lastly, there were 57 deaths in the deferred treatment group compared to 47 in the immediate treatment arm.

These findings confirm that ART significantly improves the health of an individual with HIV and reduce the person’s risk of developing AIDS and serious health issues, and that early diagnosis and treatment are key to maximising these benefits and reducing risk, according to the presenters.

Source: NIH/National Institute of Allergy and Infectious Diseases

Categories : HIVTags :

SA HIV Clinicians Update Dolutegravir Guidelines

On By ModernMedia
HIV themed candle
Image by Sergey Mikheev on Unsplash

The South African HIV Clinicians Society (SAHCS) have recently announced a clinical update on the dolutegravir (DGT)-based regimens for first- and second-line antiretroviral therapy. This comes in the wake of positive findings from a number of clinical trials.

The clinical guidelines are available for download as a PDF.

“Based on data from several recent trials, we now recommend that all patients > 10 years old and 35 kg on tenofovir/emtricitabine (or lamivudine)/efavirenz (TEE/TLE) or NVP-based regimens be switched to tenofovir/lamivudine/dolutegravir (TLD) regardless of the viral load (VL) result. In addition, all patients > 10 years old and > 35 kg on a regimen of two nucleoside reverse transcriptase inhibitors (NRTI) with a boosted protease inhibitor (PI) (eg, lopinavir/ritonavir (LPV/r) or atazanavir/ritonavir (ATV/r)) and a suppressed VL can be switched to TLD, regardless of prior resistance patterns or treatment history.”

In South Africa, pre-treatment resistance to nonnucleoside reverse transcriptase inhibitors (NNRTI)-based antiretroviral therapy regimens has been rising. Meanwhile, DTG has a higher barrier to resistance and reduced side effects. This prompted the Department of Health to recommend that patients on NNRTI-based ART regimens be switched to DTG-based regimens. This transition is slower than desired partly because a documented suppressed VL is required prior to switching from TEE/TLE to TLD. Since this recommendation was first made, evidence from several trials (NADIA, VISEND and ARTIST) has demonstrated that tenofovir with lamivudine can be safely and effectively recycled from a first- to a second-line regimen. Therefore, the SAHCS has stated that “in patients with virological failure on a TEE or TLE regimen a single drug can be switched (efavirenz to dolutegravir ie, TLD as secondline), resulting in virological suppression comparable to or better than alternative second-line options.”

The guidelines also outline the results of the NADIA, VISEND and ARTIST trials conducted in southern African countries, as well as the single-arm DAWNING trial.

Source: South African HIV Clinicians

Categories : HIVTags :

Scientists Find Second HIV Patient Achieved a ‘Sterilising Cure’

On By ModernMedia
HIV infecting a human T9 cell. Credit: NIH

In a study published in the Annals of Internal Medicine, scientists have reported the identification of a second HIV patient who appears to have completely eliminated HIV from their systems in a ‘sterilising cure’. 

During infection, HIV creates a viral reservoir by inserting copies of its genome into a cell’s DNA. This allows the virus to escape from anti-HIV drugs and the body’s immune response. In most people, new viral particles are constantly made from this reservoir. Antiretroviral therapy (ART) can prevent new viruses from being made but cannot eliminate the reservoir, necessitating daily treatment to suppress the virus.

Some, known as ‘elite controllers’, have immune systems that are able to suppress HIV without the need for medication. Though they still have viral reservoirs that can produce more HIV virus, a type of immune cell called a killer T cell keeps the virus suppressed without the need for medication.

Xu Yu, MD, a physician investigator at Massachusetts General Hospital, led a research group that identified one patient with no intact HIV viral sequence in her genome, indicating that her immune system may have eliminated the HIV reservoir: a sterilising cure. When they sequenced billions of cells from this patient, known as the San Francisco Patient, searching for any HIV sequence that could be used to create new virus, they found no sign. This extraordinary finding, the first known incidence of a sterilising cure without a stem cell transplant, was reported in Nature in 2020.  

Now, Dr Yu’s group reports a second untreated HIV-infected patient, known as the Esperanza Patient who also has no intact HIV genomes found in more than 1.19 billion blood cells and 500 million tissue cells sequenced. This may represent a second instance of a sterilising cure.

“These findings, especially with the identification of a second case, indicate there may be an actionable path to a sterilizing cure for people who are not able to do this on their own,” said Dr Yu.

She further explains that these findings may suggest a specific killer T cell response common to both patients driving this response, with the possibility that other people with HIV have also achieved a sterilising cure. If researchers can figure out the immune mechanisms behind this response, they could develop treatments that teach others’ immune systems to mimic these responses in cases of HIV infection.  

Yu adds: “We are now looking toward the possibility of inducing this kind of immunity in persons on ART through vaccination, with the goal of educating their immune systems to be able to control the virus without ART.”

Source: EurekAlert!