Tag: HIV treatment

Categories : Gender HIVTags :

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

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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

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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

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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

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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

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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

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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’

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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!