Category: HIV

Categories : HIVTags :

Stigma, Lack of Awareness Holding Back Use of HIV Prevention Pills, Experts Say

On By ModernMedia

By Thabo Molelekwa for Spotlight

Photo by Miguel Á. Padriñán: https://www.pexels.com/photo/syringe-and-pills-on-blue-background-3936368/

Over the last four years South Africa has taken large strides in making HIV prevention pills available at public sector clinics, but uptake has not been as good as some may have hoped. Thabo Molelekwa asks several experts why this might be.

HIV prevention pills, also referred to as oral pre-exposure prophylaxis (PrEP), contain a combination of two antiretroviral medicines. They  are highly effective at preventing HIV infection when taken as prescribed by someone not living with HIV.

But while the pills are now available through most public sector clinics in the country, not as many people are using them as one might have expected. According to the most recent estimates from Thembisa, the leading mathematical model of HIV in South Africa, only around 4% of sexually active adolescent girls and young women used PrEP in 2022. This is a substantial improvement on 0.6% in 2020, but given that the rate of new HIV infections in adolescent girls and young women has remained stubbornly high, one may have expected this number to be higher by now.

“So the rates of uptake are definitely increasing in South Africa, but not to the point that we would hope. There’s still definitely a gap between people who would benefit from being on PrEP or alternative HIV prevention methods and those who are actually accessing the biomedical daily oral prevention,” says Cheryl Hendrickson, a Senior Researcher at the Health Economics and Epidemiology Research Office (HE²RO) at the University of the Witwatersrand.

Ongoing stigma

One explanation for uptake not being better is the ongoing impact of HIV-related stigma. A recent study conducted among young people in Gauteng found that stigma and a lack of confidentiality continue to impede PrEP adoption. The researchers identified several barriers for PrEP-naive participants, including limited knowledge, negative staff attitudes, and misconceptions about side effects. Structural factors like healthcare provider bias and a lack of culturally sensitive interventions were also found to hinder PrEP uptake. The research was conducted by HE²RO – Hendrickson was a co-author.

“Participants were worrying about their families or friends thinking they were taking ARVs,” says Constance Mongwenyana-Makhutle, a research associate and co-author of the study.

Professor Linda-Gail Bekker, CEO of the Desmond Tutu HIV Centre, also emphasises the persistent role of stigma. “People don’t want to be associated with HIV, HIV risk or any misconception that they may be living with HIV and on antiretroviral therapy,” she tells Spotlight.

The perception around PrEP, says Dr Fareed Abdullah, Director of AIDS and TB Research at the South African Medical Research Council, is similar to that of contraception. “Basically, a young person would consider it an admission that they are sexually active and consider themselves to be at risk of HIV; thereby inviting judgement and stigma from others, especially healthcare workers,” he says.

Not enough awareness?

Closely related to the issue of stigma is awareness. Here COVID-19 may have played a role. As the provision of PrEP through public sector clinics gained momentum in 2020, many potential PrEP users would have stayed away from clinics due to pandemic-related restrictions and fear of contracting SARS-CoV-2. The pandemic also meant that any plans to build awareness of PrEP would have had a hard time finding purchase, at least in 2020 and 2021.

Reflecting on past HIV awareness campaigns, Bekker stresses the need for increased public demand creation for PrEP

“I think we have not had enough public demand creation- if you think of the campaigns for getting people to take up COVID vaccines….then we really haven’t done enough in this regard. It is a new concept- a pill a day to prevent HIV ……and so people need to have the idea socialised and normalised so that there is also a reduction in stigma,” she says.

What happens at the clinic

Another barrier to PrEP uptake is likely that while PrEP is being made available through public sector clinics, not everyone feels welcome at, or like to visit, their local clinic.

Bekker says youth complain that government clinics are often a barrier for them to access PrEP. “Their hours, their long queues, their discrimination and sometimes the prejudicial attitudes drive young people away,” she says.

Bekker argues that some of these barriers would be removed if HIV prevention measures was taken outside of health facilities and into community spaces.

“PrEP for young people in the public sector is free. If they want to use private pharmacies though, they would need to pay currently. I think more can be done to make PrEP and other sexual and reproductive health services more readily available so that young people, in a way, have no excuses not to make sure they are using them … colleges, universities and even secondary schools could also reach more young people. If we want to reduce STIs and unintended pregnancies in our adolescents, we are going to have to be sure there are very few barriers to these contraceptive and prophylactic services,” says Bekker.

Hendrickson points out that there are several projects around the country that are looking at alternative service delivery methods. “There’s a project that’s looking at prep delivery in pharmacies. Currently, they are providing oral prep, and hopefully soon, they will provide injectable prep within several pharmacies in Gauteng and the Western Cape,” she says. According to her, the pharmacy model appeals especially to men.

Healthcare worker attitudes and training

Related to the issue of visiting public healthcare facilities to access PrEP, healthcare worker attitudes and training has also been flagged as a concern.

Bekker says some health care professionals are not trained to deal with young people in their diversity. “Adolescents are a very distinct population – they can be offended, they value their privacy, and they can make health choices and decisions but need supportive, empathic and tailored information that they can use,” she says.

Abdullah makes a similar point. If some health care workers are properly trained, can identify people at high-risk and understand the efficacy of the intervention, then the vast majority would follow and offer the service in a professional manner, he says.

Ritshidze, a community-based healthcare monitoring group, say they have observed an increase in the number of healthcare facilities where staff say they prioritise offering PrEP to members of key populations such as young women and adolescent girls or men who have sex with men. Of 394 clinic staff surveyed earlier this year, 97% said they prioritise young women and adolescent girls.

But when Ritshidze asked users of healthcare facilities whether they’ve been offered PrEP, the numbers were much lower. “Compared to data collected in 2022, our 2023 data report a lower percentage of people saying they have been offered PrEP for most population groups,” Ritshidze say in a recent report. Complaints about negative staff attitudes have been a running theme in Ritshidze’s reports on public sector healthcare facilities over the last three years.

Actual and perceived risk

Abdullah suggests another barrier to PrEP uptake. There is a perception that HIV is no longer an urgent priority and that the risk of infection is low. This, he says, has led to lower public awareness of the importance of behaviour change and the need for young people at risk to protect themselves.

Recent data from a Human Sciences Research Council survey and the District Health Barometer indicate that condom use is declining in South Africa. While the reasons for the decline are not clear, one theory is that it is driven by the perceived risk of HIV infection having reduced over time.

Will more choice help?

Currently only oral PrEP is routinely available in the public sector, but PrEP in the form of a two-monthly injection and a monthly vaginal ring have been approved by the South African Health Products Regulatory Authority and is being offered to people taking part in pilot projects. It is likely that the prevention injection will become much more widely available once its price drops sufficiently – which is anticipated to happen once generic manufacturers enter the market in around three years’ time. Products that combine PrEP and a contraceptive into a single pill or injection are also under development.

Mitchell Warren, director of Avac, a global HIV advocacy organisation, is optimistic about people being offered a choice between the three types of PrEP. While condoms were widely available in public clinics in the 1990s, Warren says he noted the desire of people to buy condoms from spaza shops, shebeens, or pharmacies. This didn’t replace clinic supplies, he clarifies, but it did bring into sharper focus the importance of providing choice to people.

“But even with three different PrEP options, what we clearly have known for many years now is that PrEP is not only about the products, PrEP is really a programme, helping people identify not just their personal risk, but their desires, what they want and need out of relationships,” he says.

Government perspective

Foster Mohale, spokesperson for the National Department of Health, says the department is aware of reports of youth experiencing problems accessing PrEP at healthcare facilities.

Mohale maintains that healthcare workers are sufficiently trained to provide comprehensive HIV prevention services to all groups of people. He says that clinicians, counsellors, health promotors and peer educators have access to online training platforms. “These training modules are availed offline on flash drives to facilitate access to facilities and health care providers that do not have easy access to wifi or data to access the online version of the training materials,” he says.

Republished from Spotlight under a Creative Commons licence.

Source: Spotlight

Categories : HIVTags :

SA Company Set to Manufacture HIV Prevention Ring

On By ModernMedia

By Catherine Tomlinson for Spotlight

Photo by Miguel Á. Padriñán: https://www.pexels.com/photo/syringe-and-pills-on-blue-background-3936368/

A company headquartered in Johannesburg will start making flexible silicone rings to protect women from HIV. The move signals a strong vote of confidence in an African firm to supply the ring at adequate scale and affordable prices, and a crucial step to making the continent self-reliant, reports Catherine Tomlinson.

A South African company has secured the rights to manufacture a vaginal ring used to prevent HIV infection. The ring, which is inserted and removed by the user, provides protection for a month, after which it has to be replaced with a new ring. The ring contains an antiretroviral drug called dapivirine.

While studies show that the dapivirine vaginal ring is less effective at preventing HIV than HIV prevention pills and injections, it has benefits over other tools that have led the World Health Organization (WHO) to recommend its inclusion in the package of sexual health services available to women.

One advantage of the ring over HIV prevention pills is that it can be used discreetly by women, allowing users to use the ring without having to negotiate or discuss its use and purpose with their sexual partners. This is particularly important in the context of South Africa where women face high rates of gender-based violence, which erodes their autonomy over their bodies and sexual and reproductive health.

“We need to give women more control over their health and bodies and access to a range of safe and effective options, including the dapivirine ring, to choose from so they can decide to use what works best for them at different times of their lives,” wrote several prominent women African activists in 2022.

Limited access

While the WHO recommended that the ring is offered to women, its current price is a barrier to broad use and rollout in South Africa. The only dapivirine vaginal ring approved by the South African Health Products Regulatory Authority that is currently available in the country is called the DapiRing.

The DapiRing is manufactured by a Swedish company, Sever Pharma Solutions, under a licence from the Population Council (formerly the International Partnership for Microbicides). It can be bought in South Africa’s private sector for R320, excluding dispensing fees.

The DapiRing is not available in South Africa’s public sector outside of study and pilot sites, as the National Essential Medicines List Committee, the body that determines which health technologies should be available in the country’s public health facilities, determined that the product is unaffordable at its current price. They estimate that the product will become affordable for South Africa’s public sector at a threshold price of R52 per ring.

Local company to boost access

The Population Council, the entity that owns the intellectual property on the dapivirine vaginal ring, selected South African pharmaceutical company Kiara Health to manufacture and supply the ring across Africa.

Kiara Health’s CEO, Dr Skhumbuzo Ngozwana, told Spotlight that while it is not yet known what the price of the Kiara manufactured ring will be, it is expected to be lower than the current price of the Swedish-manufactured DapiRing.

Licensc to manufacture

The council told Spotlight that the initial focus of the licence and partnership will be to develop manufacturing capacity at Kiara Health to supply the dapivirine vaginal ring across Africa. In the long term it is hoped that Kiara will be able to serve markets outside of Africa where there is a need for the ring.

The Population Council’s selection of an African-based manufacturing partner is notable as holders of intellectual property protections on HIV health technologies have typically sought out companies in Asia, and India in particular, as manufacturing partners.

Professor Linda-Gail Bekker, CEO of the Desmond Tutu HIV Foundation, told Spotlight: “If the “COVID-19 pandemic taught us anything, it is the value of being self-reliant as a region – being able to manufacture the vaginal ring is a step closer to Southern African self-reliance.”

Ngozwana said that Kiara Health appreciates that the Population Council have bucked the trend by not going to the East. “[A]ll these new technologies tend to go to the East, but instead they’ve partnered with an African company”.

Dapivirine vaginal ring. Credit: Columbia University Mailman School of Public Health

He added that future technology transfers to other manufacturers in Africa may be pursued if there is a need.

Exclusive supply licence

The Council told Spotlight that it intends to pursue an exclusive supply licence with Kiara Health for the sole supply of the dapivirine ring in Africa. The pursuit of an exclusive supply licence is a strong vote of confidence by the Population Council in the ability of Kiara Health to supply the ring at adequate scale and affordable prices.

Since Kiara Health’s exclusivity is for the supply of the ring, if there is a need, the company will be able to supply a dapivirine vaginal ring that is made by the Population Council’s Swedish manufacturing partner, Sever Pharma Solutions, that is already widely authorised for use in countries in Africa.

This would also guard against supply shortfalls that sometimes occur when only one manufacturer supplies a market, doctor Brid Devlin, the Population Council’s chief scientific officer, told Spotlight. “We would have two registered manufacturers right out the gate to guard against any shortfalls and have the opportunity to continue the supply as the demand grows.”

Why Kiara Health was chosen

Devlin added that the Population Council did not have a formal bid process through which Kiara Health was selected as the manufacturing partner for the ring, but rather that Kiara Health was selected following years of engagement with the company.

“We had a team that went to Kiara last year to see this site and it was a really impressive operation, both in terms of the staff but also the entire manufacturing operation,” she said.

Ngozwana told Spotlight that Kiara Health has existing manufacturing facilities in Johannesburg where capacity to produce the ring will be established.

Kiara Health’s manufacturing facilities already hold the quality assurance certifications (cGMP certification) required to manufacture medicines and have adequate space in Johannesburg to establish and scale manufacturing capacity for the ring, Ngozwana told Spotlight.

What is needed to manufacture the ring locally?

Critical steps include technology transfer, securing financing, procuring and importing manufacturing equipment, developing validation batches, and seeking regulatory approvals.

At this stage, there are still unknowns regarding the extent of data and testing that will be required to gain regulatory approval of Kiara Health’s dapivirine vaginal ring. To aid regulatory authorisation, Ngozwana and Devlin noted that Kiara Health would use the same manufacturing technology and inputs, including active pharmaceutical ingredients (API) used by Sever Pharma Solutions. This will require Kiara Health to import manufacturing equipment and API from Europe.

However, in the long term, Ngozwana said that Kiara Health would hope to increasingly procure manufacturing inputs, including potentially dapivirine API from the Pretoria-based API manufacturer CPT Pharma. (Spotlight previously reported on CPT Pharma’s work on API production here).

Ngozwana and Devlin told Spotlight that the anticipated time-limiting factors for establishing manufacturing capacity are securing financing and procuring and importing manufacturing equipment.

Funding has long been a challenge for African-based pharmaceutical companies since it has historically been scarce and only available on unfavourable terms. However, Ngozwana told Spotlight that Kiara Health is already engaging potential funders for support and exploring different financing sources, including grants and debt instruments.

Ngozwana and Devlin noted that technology transfer, which is a process for transferring manufacturing skills and knowledge, has already begun.

Can this license boost further domestic manufacturing capacity?

While vaginal rings are a relatively new type of health technology, they have multiple potential applications. A vaginal ring to prevent pregnancy has been available since the early 2000s and work is underway to develop a ring that is effective in combating both HIV and pregnancy. A dapivirine ring that reduces one’s risk of contracting HIV for three months – as opposed to one month – is also under development.

Kiara Health will seek to position itself to manufacture other vaginal rings entering the market, Ngozwana said. He added that in the long term, the company hoped that the partnership with the Population Council will be broadened to allow for local manufacturing of other sexual and reproductive health technologies in their product portfolio.

Republished from Spotlight under a Creative Commons licence.

Source: Spotlight

Categories : HIVTags :

Pilot Project in SA Now Offering HIV Prevention Injection

On By ModernMedia
Taking antiretrovirals to prevent HIV infection is available in the form of pills, vaginal rings, and injections. (File photo: Nasief Manie/Spotlight)

A new HIV prevention injection is now available to a select number of people in South Africa. That a single shot provides two months of protection is one of the injection’s major selling points. In this story, Elri Voigt unpacks how much of the jab is available, who is choosing to get it and what other anti-HIV drugs are being rolled out.

By Elri Voigt for Spotlight

Earlier this month, a young person in Cape Town became one of the first people in the country to receive a new HIV prevention injection outside of a clinical trial. The injection contains a long-acting formulation of the antiretroviral drug cabotegravir (CAB-LA for short). It provides two months of protection against HIV infection per shot.

“We were excited and nervous at the same time because (we) didn’t know how this person is going to react to an injection,” said Pakama Mapukata, a nurse and study coordinator. She added that the first person who received the CAB-LA injection responded well and told her that the injection was less painful than an sexually transmitted infection (STI) injection they had to receive in the past.

While the injection is not readily available for most members of the public just yet, a select number of people in the country will be able to access it via several implementation studies, also called pilot projects. One of these pilots is a study called FAST PrEP, conducted by the Desmond Tutu Health Foundation (DTHF) in Cape Town. Technically, access to the injection is limited to a FAST PrEP sub study called Prepare to Choose.

Taking antiretrovirals to prevent HIV infection is referred to as pre-exposure prophylaxis (PrEP). PrEP is available in the form of pills, vaginal rings, and injections.

According to Elzette Rousseau, a social behavioural scientist and the lead co-investigator in the implementation team for FAST PrEP, on the first day it was offered, five people opted to get the CAB-LA shot. “The first two, at least, that came through was a young MSM [men who have sex with men] and one was a young woman, which is definitely exciting because that is the population that we would want to come to our services which will benefit most from it,” she said. As of 21 February, 19 injections in total had been administered.

‘Real-world experience’

Professor Linda-Gail Bekker, Chief Executive Officer of the DTHF and Principal Investigator of the study, explained that once CAB-LA demonstrated efficacy in phase three clinical trials, it was decided to first do some implementation science studies in the country, alongside the other new PrEP option which is the dapivirine vaginal ring (DPV-VR), before rolling it out in the public sector.

Both the CAB-LA injection and the dapivirine ring have been approved by the South African Health Products Regulatory Authority (SAHPRA). Prevention pills, also called oral PrEP, were approved several years earlier and are already widely available in the public sector and at pharmacies.

She explained the idea is that these implementation studies can help transition the product from the clinical trial setting to a real-world rollout in the public sector. Essentially the pilots would serve as a way of introducing the injectable and the ring on a smaller scale and lessons learnt from the pilots could be used to inform the future, larger rollout of these products. It also helps pick up any potential issues or safety concerns that may not have been seen in the clinical trials.

She added that pilot projects also help inform what the demand for a product like CAB-LA and the DPV-VR will be, which can help with advocacy efforts and give the manufacturers and companies who create generic products an idea of whether it’s worth investing in these products.

“There really are limited pilots going on in the country to date,” Bekker said. The pilots that are offering CAB-LA in addition to the DTHF are being conducted by Ezintsha and Africa Health Research Institute (AHRI), as well as the Wits Reproductive Health and HIV Institute (Wits RHI). Spotlight reported on this in-depth last year.

CAB-LA delays

Bekker told Spotlight the volumes of CAB-LA available in the country remain constrained for now.

While SAHPRA approved the injection in late 2022, limited supply and the product’s high price has limited uptake around the world. A recent HIV investment case for South Africa found the injection not to be cost-effective at the current price compared to PrEP in the form of pills. For now, the only supplier of CAB-LA is the pharmaceutical company ViiV Healthcare. Generic products are anticipated to enter the market in three to four years.

Despite SAHPRA approval for the product, the pilot projects have experienced delays in getting CAB-LA to their participants. As Spotlight reported last year, the National Department of Health stated that there were challenges getting the CAB-LA injections donated for the implementation studies into the country as the packaging did not meet South African regulatory requirements.

Bekker said that an alternative is to import CAB-LA through a phase 3b study (in this case the Prepare to Choose study), approved by SAHPRA’s Clinical Trial committee. Writing up protocols and having the study approved by an ethics committee and SAHPRA took some time, and once it was approved, CAB-LA still needed to be imported and ViiV Healthcare had to ramp up manufacturing to meet demand.

Bekker told Spotlight that to date, CAB-LA has not yet been purchased by the National Department of Health for distribution to the public, and the only other way to get CAB-LA into the country will be through a donation by the United States President’s Emergency Plan for AIDS Relief (PEPFAR).

“PEPFAR has been able to import the product into Zambia and Malawi…as the first two PEPFAR countries to get it as a PEPFAR donated public rollout and we hope South Africa is in that queue further down the line,” she said.

The Prepare to Choose Study

At the moment, Prepare to Choose can only offer CAB-LA to a few hundred people. Bekker said that ideally, they would have wanted to offer all their FAST PrEP clients a three-way choice of either the vaginal ring, oral PrEP pills or CAB-LA. But for now, CAB-LA is only being offered within Prepare to Choose, which is a single-nested sub study within FAST PrEP.

Mapukata, who was present during the first CAB-LA injection in the implementation study, said it will be interesting to see what participants choose now that they have an additional PrEP option. “People have been waiting for injection for the longest time, so we are seeing lots of excitement from the participant side,” she said.

Rousseau told Spotlight that Prepare to Choose currently has enough CAB-LA doses for 900 participants over an 18-month period.

She said they have thus far observed that “people are still choosing what [PrEP option] suits them” when offering existing or potential FAST PrEP participants the choice to access CAB-LA.

So far those who have chosen CAB-LA are primarily adolescent girls and young women with an average age of 22. Some have been on PrEP before, while others are starting PrEP for the first time. “In that cohort we know that the burden of HIV exists, so that’s encouraging at this point,” Rousseau said.

Trends observed in FAST PrEP 

FAST PrEP is being implemented at 12 public sector health facilities in the Klipfontein and Mitchells Plain Health Sub-Districts in the Western Cape, as well as in four mobile clinics that operate in the area. Since the start of FAST PrEP, just under 11 000 participants have enrolled, according to Rousseau. This means that around 11 000 people have accessed either prevention pills or the DPV-VR through the study.

When FAST PrEP started, the assumption was that the study can enrol between 20 000 and 23 000 participants, but it is not necessarily targeting to enrol that exact number of participants. Rousseau added that the study currently has funding to continue offering PrEP until late next year but access to these options may potentially continue beyond that.

The study reaches participants in public sector healthcare facilities by having two peer navigators in each facility. These peer navigators are young people trained and employed by the study coordinators. They can educate and counsel young people about FAST PrEP. The study coordinators also offer training, particularly sensitisation training, to nurses and other staff members.

The four mobile clinics travel around the Klipfontein and Mitchells Plain Health Sub-Districts, particularly where there is a high incidence of HIV, as well as spaces where young people are present. These include 16 secondary schools in the area where the mobile clinics have permission to enter the school grounds.

Demand for the DPV-VR

Rousseau told Spotlight that so far, just under 200 women in the study have chosen to use the DPV-VR. However, it’s important to note that within the whole study population, not everyone is eligible to use the ring. It is currently being offered to women who are over 18, not pregnant and not breastfeeding.

She added that for participants who are eligible for both the ring and oral PrEP, the pill is still more popular – with a rough estimate of around 15% of eligible participants opting for the ring. Most participants, at this stage, who choose to use the ring are those who have tried oral PrEP first and struggle to take pills daily or found it doesn’t suit their lifestyle. Very few participants to date have started on the ring and then switched to the daily pill.

Dapivirine vaginal ring. Credit: Columbia University Mailman School of Public Health

She said the demographics of who prefers the ring over oral PrEP haven’t been explored in-depth, but it’s something that the study will be looking at and analysing data on in future.

Bekker added to this saying: “We always expected it to be a bit of a niche product because you know definitely for many the idea of swallowing a pill is perhaps an easier concept than using a vaginal ring. So, it has started slowly, we’ve now administered hundreds as opposed to thousands of rings.”

She noted that interest in the ring has built overtime and is starting to pick up more. “Our first, preliminary data suggests that the women who choose rings are coming back [for it] …they’ve decided they want to go that road and they’ve committed,” Bekker said.

Counselling for Choice

While the ring was found to be effective in two phase 3 trials, its efficacy in those trials was far from 100% and the evidence for the ring’s efficacy is generally less impressive than that for pills and the injection. Interpreting findings from PrEP trials is also somewhat muddied by whether or not pills are taken as prescribed, and the ring is used and replaced as prescribed – that a single shot provides two months of protection is one of the injection’s major selling points.

Compared to placebo, there was a 30% reduction in HIV infection for ring users in phase three trials, while there was a 50 to 60% reduction in infection when the ring went to open-label, Bekker noted.

She said that it has previously been observed that clinical trial efficacy results can differ from real-world results, particularly when it comes to HIV prevention. For instance, she said, oral PrEP in clinical trials initially showed no evidence of efficacy in the prevention of HIV in women. Yet, real-world evidence showed it works in all populations if taken as prescribed.

What both these cases have shown, according to Bekker, is that it’s not necessarily that the product isn’t working, it’s that the product isn’t always being used as intended. When it comes to the ring, she said, the drug within the ring is efficacious and will kill the virus, but the ring must be present at the time that the individual is exposed to HIV. “Once you take the ring out, the [prevention] effect is lost,” she said.

When asked how women are counselled about the ring in the FAST PrEP study, Bekker said it is done very carefully and with guidance of their peers – this is where the peer navigators play a big role.

FAST PrEP was designed using a lot of engagement from young people, Bekker said. For a year before the pilot started, a group of 100 young people from diverse populations were enrolled from the community to give feedback on how to design the pilot so it can best reach young people. This group also essentially helped troubleshoot the information coming from the pilot to ensure that the PrEP choices were communicated in an appropriate way.

“They are very instrumental at the moment in making sure that that message [on DPV-VR] is clearly communicated,” she said.

Bekker added that if an individual needs time to think about which PrEP option to use, they are advised to start with oral PrEP and that they can switch later if they want.

Mapukata explained how the counselling process plays out on the ground. Participants in FAST PrEP, once they have spoken to a peer navigator, are taken into a counselling room and given a quiz where their scores are used to indicate what PrEP option might work for them. This is used as a starting point to counsel participants about the different PrEP options and which options they are eligible for and most comfortable using.

“It’s a lot of counselling that goes in before that choice [of PrEP] is made,” Mapukata said.

Young people who are members of the FAST PrEP youth reference group speak of the project in glowing terms. “And it’s so nice because you have a variety to choose from, you’re not obligated [to only] be on PrEP, on the oral, because there’s a variety of options,” one of them told Spotlight.

Republished from Spotlight under a Creative Commons licence.

Source: Spotlight

Categories : HIV Medical IndustryTags :

First HIV Antiretrovirals Manufactured in Space Delivered Back to Earth

On By ModernMedia

For the first time, unique commercial pharmaceuticals produced using the zero gravity of outer space have been returned to Earth. After being stuck in space waiting for clearance to land, a capsule containing the small but extremely valuable cargo of HIV antiretrovirals landed in the desert in the US state of Utah. Drugs produced this way have higher purity and often improved pharmacokinetics, but have been too costly to produce until now.

In June 2023, a miniature pharmaceuticals factory built by Varda Space Industries was launched into Earth orbit. This small space startup company had only been around since 2020 – and the COVID pandemic had inspired them to look for a way to use the unique properties of space to directly benefit the health of people on Earth.

Zero gravity process can give drugs new properties

According to Varda co-founder Delian Asparouhov, gravity has significant effects somewhere between the microscopic scale and the atomic scale. This has beneficial applications in all manner of processes like crystal formation in drug manufacturing. For example, it is possible to give certain solid state pharmaceuticals improved solubility, turning a four-hour intravenous infusion into a couple of subcutaneous injections. The number of oral pills required for a treatment could be reduced. Since treatment compliance is a major obstacle to treatment, such improved drugs could significantly improve outcomes.

There are many drugs that were abandoned simply because administration was too impractical. Zero gravity manufacturing could open up these libraries of discarded drugs, Asparouhov says. It could also be possible to modify certain drugs to cross the blood–brain barrier.

Antiviral Drug Polarized crystals (photographed through a microscope) of the drug 2-3 dideoxyadenosine, also known as ddA, a drug that is closely related to AZT or azidothymidine. The antiviral effect of ddA against HIV was discovered at the National Cancer Institute. Credit: Larry Ostby (Photographer), National Cancer Institute, National Institutes of Health

Onboard the small space factory is a pharmaceutical manufacturing system designed to produce ritonavir, an antiretroviral which was initially used to treat HIV. This early antiretroviral has a number of notorious gastrointestinal and metabolic side effects. In 1998, there was a major production crisis when it was discovered that were production defects in the the oral form stemming from crystallisation problems.

Nowadays, ritonavir has been surpassed by newer antiretroviral drugs for the treatment of HIV but has been investigated for cancer treatment and during the pandemic received emergency use authorisation for COVID treatment. The samples retrieved from the capsule will only be used for evaluation purposes, to help inform the production of other pharmaceuticals.

Producing drug proteins in space is nothing new. This has been done on space stations for decades – however, these were for research purposes in developing drugs and understanding biological processes. It is only now that technology has advanced to the point where it has become cheap enough to use the unique environment of outer space to manufacture high-value products.

The capsule with its onboard factory is specially designed to be recovered and reused to minimise costs. This has only been possible thanks to rockets becoming vastly cheaper. NASA’s space shuttle cost US$65 400 for each kilogram of cargo launched into space. Today, SpaceX’s Falcon 9 rocket costs a mere 4% of that, with costs set to fall further.

Such breakneck technological development was bound to run into a snag – this one consisting of red tape. The agency that regulates commercial air and spaceflight, the Federal Aviation Administration (FAA) gave Varda a licence for their payload to be launched, but not for the capsule to re-enter the atmosphere. The vast majority of satellites don’t have to worry about that, simply burning up in the atmosphere when they can no longer function. The FAA is obviously concerned about a large module returning intact but out of control.

Eventually, after more than six months of delays and looking at alternatives such as landing in Australia instead, Varda was able to secure a re-entry permit for 21st February and its capsule returned to Earth under a parachute in the Utah desert.

Asparouhov envisions a time when much larger orbital factories produce pharmaceuticals and other valuable materials in orbit.

Categories : HIVTags :

New Trial Highlights Incremental Progress Towards a Cure for HIV-1

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Colourised transmission electron micrograph of an HIV-1 virus particle (yellow/gold) budding from the plasma membrane of an infected H9 T cell (purple/green).

Antiretroviral therapies (ART) stop HIV replication in its tracks, allowing people with HIV to live relatively normal lives. However, despite these treatments, some HIV still lingers inside cells in a dormant state known as “latency.” If ART is discontinued, HIV will awaken from its dormant state, begin to replicate, and cause acquired immunodeficiency syndrome (AIDS). To create a cure, researchers have been attempting to drive HIV out of latency and target it for destruction.

A new clinical trial led by Cynthia Gay, MD, MPH, associate professor of infectious diseases, David Margolis, MD, the Sarah Kenan Distinguished Professor of Medicine, Microbiology & Immunology, and Epidemiology, and other clinicians and researchers at the UNC School of Medicine suggests that a combination of the drug vorinostat and immunotherapy can coax HIV-infected cells out of latency and attack them.

The immunotherapy was provided by a team led by Catherine Bollard, MD, at the George Washington University, who took white blood cells from the study participants and expanded them in the laboratory, augmenting the cells’ ability to attack HIV-infected cells, before re-infusion at UNC.

Their results, published in the Journal of Infectious Diseases, showed a small dent on the latent reservoir, demonstrating that there is more work to be done in the field.

“We did show that this approach can reduce the reservoir, but the reductions were not nearly large enough, and statistically speaking were what we call a “trend” but not highly statistically significant,” said David Margolis, MD, director of the HIV Cure Center and senior author on the paper. “We need to create better approaches to flush out the virus and attack it when it comes out. We need to keep chipping away at the reservoir until there’s nothing there.”

DNA inside cell nuclei is kept in a tightly packed space by chromosomes, which act as highly organised storage facilities. When you unfurl a chromosome, you’ll find loop-de-loop-like fibres called chromatin. If you keep unfurling, you’ll see long strands of DNA wrapped around scaffold proteins known as histones, like beads on a string. Finally, when the unfurling is complete, you will see the iconic DNA double helix.

Vorinostat works by inhibiting a lock-like enzyme called histone deacetylase. By stopping this mechanism, tiny doors within the chromatin fibres unlock and open up, effectively “waking up” latent HIV from its slumber and making it vulnerable to an immune system attack. As a result, a tiny blip of HIV expression shows up on very sensitive molecular assays.

But the effects of vorinostat are short lived, only lasting a day per dose. For this reason, Margolis and other researchers are trying to find safe and effective ways to administer the drug and keep the chromatin channels open for longer periods of time.

For the study, six participants were given multiple doses of vorinostat. Researchers then extracted immune cells from the participants and expanded the cells that knew how to attack HIV-infected cells.

This immunotherapy method, which has been successful against other viruses such as Epstein-Barr virus and cytomegalovirus, involves giving participants back their expanded immune cells in the hopes that these cells will further multiply in number and launch an all-out attack on the newly exposed HIV-infected cells.

However, in the first part of this study, only one of the six participants saw a drop in their HIV reservoir levels. To test whether the result was simply random or something more, researchers gave three participants their usual dose of vorinostat, but introduced five times the amount of engineered immune cells. All three of the participants had a slight decline in their reservoirs.

But, statistically speaking, the results were not large enough to be definitive.

“This is not the result we wanted, but it is research that needed to be done,” said Margolis. “We are working on improving both latency reversal and clearance of infected cells, and we hope to do more studies as soon as we can, using newer and better approaches.”

Many of the participants in the study have been working with Margolis’s research team for years, sacrificing their own time and blood for research efforts. Their long-term partnership and commitment have been essential for data collection. The data, which follows the size of the viral reservoir in these people over years prior to this study, makes the small changes found more compelling.

“People living with HIV come in a couple of times a year, and we measure residual traces of virus in their blood cells, which doesn’t have any immediate benefit to them,” said Margolis. “It’s a very altruistic action and we couldn’t make any progress without their help.”

Source: University of North Carolina Health Care

Categories : HIVTags :

Starting HIV Treatment Early may be Key to Remission

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Colourised scanning electron micrograph of HIV (yellow) infecting a human T9 cell (blue). Credit: NIH

Some people with HIV, known as “post-treatment controllers,” have been able to discontinue their antiretroviral treatment while maintaining an undetectable viral load for several years. Starting treatment early could promote long-term control of the virus if treatment is discontinued.

Scientists from the Institut Pasteur and other institutes used an animal model to identify a window of opportunity for the introduction of treatment that promotes remission of HIV infection. The findings, published in Nature Communications, suggest that starting treatment four weeks after infection promotes long-term control of the virus following the interruption of treatment after two years of antiretroviral therapy.

These results highlight how important it is for people with HIV to be diagnosed and begin treatment as early as possible.

Research on the VISCONTI cohort, composed of 30 post-treatment controllers, has provided proof of concept of possible long-term remission for people living with HIV. These individuals received early treatment that was maintained for several years.

When they subsequently interrupted their antiretroviral treatment, they were capable of controlling viraemia for a period lasting more than 20 years in some cases. At the time (in 2013), the team leading the VISCONTI study suggested that starting treatment early could promote control of the virus, but this remained to be proven.

In this new study, the scientists used a primate model of SIV1 infection which allowed them to control all the parameters (sex, age, genetics, viral strain, etc.) that may have an impact on the development of immune responses and progression to disease.

They compared groups that had received two years of treatment, starting either shortly after infection (in the acute phase) or several months after infection (in the chronic phase), or no treatment.

The reproducible results show that starting treatment within four weeks of infection (as was the case for most of the participants in the VISCONTI study) strongly promotes viral control after discontinuation of treatment.

This protective effect is lost if treatment is started just five months later.

“We show the link between early treatment and control of infection after treatment interruption, and our study indicates that there is a window of opportunity to promote remission of HIV infection,” comments Asier Sáez-Cirión, Head of the Institut Pasteur’s Viral Reservoirs and Immune Control Unit and co-last author of the study.

The scientists also demonstrated that early treatment promotes the development of an effective immune response against the virus.

Although the antiviral CD8+ T immune cells developed in the first weeks after infection have very limited antiviral potential, the early introduction of long-term treatment promotes the development of memory CD8+ T cells, which have a stronger antiviral potential and are therefore capable of effectively controlling the viral rebound that occurs after treatment interruption.

“We observed that early treatment maintained for two years optimises the development of immune cells. They acquire an effective memory against the virus and can eliminate it naturally when viral rebound occurs after discontinuation of treatment,” explains Asier Sáez-Cirión.

These results confirm how important it is for people with HIV to be diagnosed and begin treatment as early as possible.

“Starting treatment six months after infection, a delay that our study shows results in a loss of effectiveness, is already considered as a very short time frame compared with current clinical practice, with many people with HIV starting treatment years after infection because they are diagnosed too late,” notes Roger Le Grand, Director of IDMIT (Infectious Disease Models for Innovative Therapies) and co-last author of the study.

“Early treatment has a twofold effect: individually, as early treatment prevents diversification of the virus in the body and preserves and optimises immune responses against the virus; and collectively, as it prevents the possibility of the virus spreading to other people,” adds Asier Sáez-Cirión.

Finally, these results should guide the development of novel immunotherapies targeting the immune cells involved in the remission of HIV infection.

These are the initial results of the p-VISCONTI study, which began in 2015 in collaboration with the institutions cited above and received funding from MSD Avenir and the support of ANRS Emerging Infectious Diseases as part of the RHIVIERA consortium.

1 SIV: simian immunodeficiency virus only affects non-human primates. SIV infection of animals recapitulates the key features of human HIV infection.

Source: Institut Pasteur

Categories : HIVTags :

Opinion: This is How SA can Meet its HIV Targets

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Photo by Miguel Á. Padriñán

By Yogan Pillay for Spotlight

“The path to ending AIDS is clear,” states a recent UNAIDS report. “HIV responses succeed when they are anchored in strong political leadership, have adequate resources, follow the evidence, use inclusive and rights-based approaches, and pursue equity. Countries that are putting people first in their policies and programmes are already leading the world on the journey to ending AIDS by 2030,” it reads.

Ending AIDS and the HIV epidemic mean different things to different people.

This very ambitious language is found in Sustainable Development Goal 3.3: “By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases”. The global target is to reduce the newly HIV infected population (per 1 000 uninfected population) to 0.05 by 2025 and to 0.025 by 2030.

Another version is “ending AIDS as a public health threat by 2030” which has been characterised as being “consistent with the three zeros vision: zero deaths, zero new infections and zero discrimination, operationalized as a 90% reduction of annual new HIV infections and AIDS-related deaths in 2030 compared to 2010”.

A third approach calls for countries to reach the 95-95-95 targets – 95% of people living with HIV are diagnosed, 95% of those that have been diagnosed are on antiretroviral treatment and 95% of those on treatment are virally suppressed – by 2025.

A fourth, more realistic approach, is to reduce the number of new HIV infections below the number of deaths from HIV – labelled ‘epidemic control’ – to an endemic status beyond 2030.

Regardless of the definition of ‘ending AIDS’, what should South Africa do in determining its path towards reducing the burden of HIV?

First, let’s start with what we think the HIV epidemic will look like in 2030. Whilst we do not have a crystal ball, we do have a well-recognised mathematical model – the Thembisa model, which is also used as the basis for UNAIDS’s HIV estimates for South Africa. The latest Thembisa model outputs, published last year, include projections up to 2030.

The model projects that in 2030 there will be around 128 535 new HIV infections with the bulk of these, over 54% (70 412) being young women between the ages of 15 and 24 years. Using the definition of a 90% decrease in new infections between 2010 and 2030, South Africa is projected to reach 65.7%.

The model projects that in 2030 around 8.1 million people will be living with HIV with 6.4 million being on antiretroviral treatment. The total number of AIDS deaths projected by the model in 2030 is 40 486 compared to 149 257 deaths in 2010. (This is a 72.9% reduction – not quite the 90% expected by one of the definitions noted above).

How well is the country doing in reaching the 95-95-95 targets?

According to the Thembisa model, the percentage of people ever tested for HIV stood at 83.7% in 2022 (projected to reach 86.1% in 2030). The percentage of people living with HIV who had been diagnosed was at 94.5% in 2022 and projected to reach 96.4% in 2030. The percentage of diagnosed people on treatment in 2022 stood at 77.4% and is projected to reach 81.1% in 2030.

The percentage of all people living with HIV who were virally suppressed was at 65.4% in 2022 and projected to reach 71.3% in 2030. (These percentages are slightly higher if a viral load cut-off of 1000 copies/mL rather than 400 is used). This means only one of the 95s (percent diagnosed) is expected to be reached. (If the third 95 is defined as percentage of people on HIV treatment who are virally suppressed, rather than percentage of all people living with HIV who are virally suppressed, it will also be met.)

A more optimistic picture has been reported by the Human Sciences Research Council (HSRC) through their recently completed national survey. This survey found that 90% of 15-year-olds and older living with HIV knew their status (this included self-reported status), with 91% of them on treatment, and 94% of those on treatment being virally suppressed (at the 1000 copies/mL threshold).

Based on the Thembisa projections, South Africa is not expected to reach epidemic control by 2030. So, what needs to be done to achieve significantly fewer new infections and deaths?

What to do

In his address to the 2023 South African AIDS conference, the Minister of Health outlined what the Department of Health considered as necessary. He noted that the country has achieved 94:77:92 against the UNAIDS targets – far lower than the HSRC survey found. This means that, according to the Department’s data, there are over two million people who are living with HIV but not on treatment and a further 1.6 million people who are on treatment but are not virally suppressed. This is far higher than the 1.9 million that the HSRC survey suggests are not on treatment and not virally suppressed.

Regardless of which data is correct, it is urgent that these patients are found, initiated on treatment and supported to reach viral suppression.

While the Minister did not quantify the number of people living with HIV who are not being reached, he did outline the following interventions that he proposed should be prioritised:

  • Immediate implementation of the revised and consolidated ART Clinical Guidelines, which includes an integrated approach on prevention of vertical transmission, a focus on TB/HIV given high levels of coinfection, and differentiated service delivery.
  • A focus on the 100 identified health facilities which are lagging in reaching the 2nd and 3rd 95s (treatment coverage and viral suppression).
  • The need to close the testing and treatment gaps for men and children through HIV self-testing and index testing (an approach whereby the exposed contacts of an HIV-positive person are notified and offered an HIV test).
  • A focus on re-engaging those who have stopped taking treatment and scaling up of community treatment, 3-month dispensing of treatment medication as well as the use of community health workers in tracking and tracing people living with HIV.
  • A greater effort on combination prevention, using all currently available prevention methods as well as Cab-LA, which is an antiretroviral HIV prevention injection that provides two months of protection per shot.

These are well known interventions and if health workers and communities are committed to their urgent and full implementation, it is possible to achieve further reductions in new HIV infections, as well as further reductions in death. However, as most deaths in people living with HIV are due to TB, a greater focus should be placed on testing people living with HIV for TB  – given the estimated 59% co-infection rates; and ensuring that they are successfully treated and initiating those that test negative for TB, on TB preventive therapy.

How do the Minister’s prescriptions align with the recently completed HIV investment case?

As recently reported in Spotlight, the only HIV intervention found to be cost saving for the health system in South Africa was condoms. However, the recent HSRC survey found that reported condom use at last sexual encounter declined in all age categories. The 2017 survey found that 68% of males aged 15-24 years reported condom use, compared to 50.6% in the latest report. Similarly, 53.4% of males aged 25-49 years reported condom use in 2017 compared to 44% in 2023.

Whilst the Minister noted in his speech at the South African AIDS conference the availability of Cab-LA for HIV prevention, the investment case found that at the current price, this was not a good investment and unaffordable! The investment case outputs suggest that it was most cost effective to increase HIV self-testing, focusing on improving linkage to treatment, as well as increasing the rate of testing infants for HIV at 10 weeks after birth.  It is therefore important to prioritise HIV interventions, as noted in the investment case, given that the National Treasury has reduced the HIV conditional grant by R1 billion and that the National Strategic Plan for 2023-2028 is not fully funded!

In UNAIDS’s path to ending AIDS, the organisation suggests what countries can do to intervene. These include: political commitment to ending AIDS, respecting human rights, engaging affected communities, removing criminalising policies and laws, addressing gender inequities, stigma and discrimination, as well as a focused approach to prevention. Some of the barriers to ending AIDS are listed as: inadequate prevention programmes, large treatment gaps, and lack of sufficient funding.

In summary, to respond to the call to end AIDS by 2030:

Firstly, it is critical to agree on its definition.

Secondly, it is important to have accurate data, including at sub-national level given that national averages hide variability by province and district. District level data by sex, age and by key populations will allow a more targeted approach to reaching those that the health system typically does not reach.

While South Africa largely funds much of its HIV response – despite the reduction noted above, the possibility of reduced external funding – through PEPFAR (a US government’s effort to address HIV globally) and The Global Fund (an international financing and partnership organisation to fight AIDS, TB and Malaria) in the future, requires the country to move to a more efficient HIV response, with more precise targeting and with greater levels of accountability. For this more granular and real time data will be required.

*Dr Pillay is extraordinary professor at the Department of Global Health, Stellenbosch University and director for HIV and TB delivery at the Bill and Melinda Gates Foundation.

Note: Spotlight receives funding from the Gates Foundation, but is editorially independent and a member of the South African Press Council. The views expressed in this opinion piece are not necessarily shared by Spotlight.

Republished from Spotlight under a Creative Commons licence.

Source: Spotlight

Categories : General Interest HIVTags :

Interview: “I Used That Anger to Feed My Activist’s Soul,” Says Former TAC General Secretary

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Dr Vuyiseka Dubula-Majola, the former General Secretary of the Treatment Action Campaign, reflects on her journey and new role at the Global Fund. PHOTO: Joyrene Kramer

By Biénne Huisman for Spotlight

Dressed in a dark jacket, rain is pelting Vuyiseka Dubula-Majola’s face as she rushes past bare trees in Geneva, Switzerland. Along with her two children, Dubula-Majola has newly moved into a house in nearby Genthod, from where she commutes to work by train.

In October, the Global Fund to Fight AIDS, Tuberculosis [TB] and Malaria, appointed Dubula-Majola as head of their community, rights and gender department. The Global Fund has allocated tens of billions of dollars around the world to fight HIV since its inception in 2002.

Five weeks into the job, Dubula-Majola tells Spotlight that a big challenge for her will be to hone a new tool – that of diplomacy.

Laughing, the former General Secretary of the Treatment Action Campaign (TAC) says that in the past, diplomacy has not been her greatest strength.

“In this new job, I am required to be diplomatic,” she says. “Basically, diplomacy is being nice in the face of atrocities, and I am not that person. So it will be a huge challenge for me, it’s going to take a shift. I will have to keep asking myself, ‘what value I can add in this position?’ While developing new tools and new ways of fighting, without being the noisy person in the room.”

The power of collective action

Known for not mincing her words, the activist-scholar is talking to Spotlight over Zoom while walking to the Global Fund’s offices in central Geneva. She adds: “Activists don’t like bureaucracies by nature, but you have a voice here. You have political currency to shift things. It’s a tough one, but I’m there.”

In a 2014 TedX talk hosted in London, an inflamed Dubula-Majola told the audience that she is angry – angry with her father, angry with her government, angry at everyone. But that she was using her anger to fuel her work.

Vuyiseka Dubula-Majola was recently appointed at head of the Global Fund’s community, rights and gender department. PHOTO: Supplied

While she is in Switzerland, Dubula-Majola’s heart still brims with African proverbs, such as: “When spider webs unite, they can tie up a lion.” She has experienced the power of such collective action first-hand at the TAC, but now she’ll be applying it on a different stage. Indeed, her new job is “to ensure that the Global Fund strongly engages civil society and promotes human rights and gender equality”, with a particular focus on supporting community led organisations.

As a role model for her new diplomatic duties, Dubula-Majola cites American public health official Loyce Pace. “Loyce Pace who runs the health program in the United States government, she is very effective in what she does while hardly saying anything in public. But she is shifting norms – bringing priority to black and poor people. She uses her allies and many other people similar to her to say things louder than she could…I guess this is another step of growth in my activist journey – to still be as effective, as radical, the very same eagerness and passion, but silently.”

‘There was no time to dream’

Dubla-Majola grew up in a village near Dutywa in the Eastern Cape. Aged 22 in Cape Town in 2001, she spiralled with depression after being diagnosed with HIV. But instead of resigning herself to what was then still a death sentence for most people, she joined the TAC – working night shifts at the McDonalds drive-through in Green Point, while by day she joined the fight to bring antiretrovirals and other medicines to South Africa.

“As a 22-year-old, I did not have fun, there was no time to dream,” she recalls. “I was fighting for my life and the lives of others. I never thought I would have children, I never thought I would get married, I never thought I would love again. Because there was also the issue of who infected me, how did this happen? You start resenting relationships.”

At the forefront of social justice activism for most of South Africa’s young democracy – a role model for people living with HIV, and for those fighting inequality – Dubula-Majola lead the TAC from 2007 to 2013, after which she joined Sonke Gender Justice as director of policy and accountability. She holds an MA in HIV/AIDS management from Stellenbosch University; her PhD from the University of KwaZulu-Natal examined “grassroots policy participation after a movement has succeeded to push for policy change,” using MSF’s [Médecins Sans Frontières] pioneering antiretroviral sites in Khayelitsha and Lusikisiki as samples.

‘Build and regain the dignity of poor people’

In 2018, when Stellenbosch University offered her a job as director of its Africa Centre for HIV/AIDS Management, Dubula-Majola was circumspect. Why take up appointment at a white male-dominated institution shackled by slow transformation, in an elitist town? But she took on the challenge to become the transformation she wanted to see.

Dubula-Majola tells Spotlight that while relishing the privilege of academia – a space to reflect – it saw her away from “the heat of the activist fire” for too long. Five years later, a new challenge awaits.

Reflecting on Stellenbosch, she says: “This [job at the Global Fund] is even harder, because it’s not just one country, one university. This is all the continents of the world. All of them facing the same thing, the struggle here is to build and regain the dignity of poor people around the globe.”

Despite her early misgivings about relationships, Dubula-Majola married fellow TAC activist, Mandla Majola. Their children, now aged 10 and 16, are HIV-negative. Presently Majola is helping with their friend Zackie Achmat’s independent campaign for the 2024 general elections, after which he will join his wife in Geneva. The family will unite in Switzerland for Christmas though – “which will be the most miserable and cold Christmas,” says Dubula-Majola, laughing. “It will be our first winter Christmas and our last. As we just arrived a month ago, it doesn’t make sense to travel back to South Africa for the holidays.”

Overall she says she remains hopeful, adding that movements like #MeTo are lessons in global solidarity.

Her thoughts on continuing the fight against HIV: “It is up to HIV positive people, and those who want to remain HIV negative, to steer towards an AIDS-free generation. We must stop complaining, thinking politicians will do everything for us, and do it ourselves.”

Meanwhile, Global Fund representatives have voiced confidence in Dubula-Majola’s ability to lead. Marijke Wijnroks, head of the organisation’s strategic investment and impact division, said in a statement: “Following an extensive search process, I am delighted to say that we found the ideal person for this role. As a person living with HIV, Vuyiseka’s lived experience and leadership style are well aligned to what we need from this critical role.”

Note: Dubula-Majola is a former General Secretary of the TAC. Spotlight is published by SECTION27 and the TAC, but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.

Republished from Spotlight under a Creative Commons Licence.

Source: Spotlight

Categories : HIV PaediatricsTags :

Treating Newborns with HIV in 1st 48 Hours may Result in Medication-free Remission

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Photo by Christian Bowen on Unsplash

An unexpectedly high percentage of children, who were born with HIV and started treatment within 48 hours of life, exhibit biomarkers by two years of age that may make them eligible to test for medication-free remission, according to a multinational study published in The Lancet HIV.

“Moving away from reliance on daily antiretroviral therapy (ART) to control HIV would be a huge improvement to the quality of life of these children,” said Protocol Co-Chair and senior author Ellen Chadwick, MD, at Ann & Robert H. Lurie Children’s Hospital.

Conducted in 11 countries including South Africa, the proof-of-concept study was charged with replicating the case of HIV remission as seen in the “Mississippi baby” that was reported in 2013. In that case, the infant started ART at 30 hours of life, was treated for 18 months, and achieved 27 months of ART-free remission before the virus rebounded. Typically, if ART is stopped, the virus rebounds within a month.

The study included a three-drug ART regimen initiated within 48 hours of life, with the fourth drug added within 2-4 weeks. This is very early treatment compared to the standard of care where three-drug ART may not begin until 2-3 months of age.

In the US, however, based on earlier findings from this study, very early treatment is now the norm for infants at high risk of acquiring HIV infection from their mother.

“With earlier treatment, we hope to limit or prevent the establishment of viral reservoirs in the body. These viral reservoirs hold small amounts of hidden virus which are hard to reach with ART. By shrinking these reservoirs, we expect to increase the amount of time that patients can be in remission, without needing daily ART,” said co-author and Protocol Co-Chair Jennifer Jao, MD, MPH, from Lurie Children’s.

Dr Chadwick adds: “Another benefit of smaller viral reservoirs might be that newer treatments such as long-acting antibody therapies or therapeutic vaccines could potentially be used instead of daily ART.”

“Our results show a higher percentage of children might be eligible to interrupt therapy than we expected, and the next step is to stop ART and see how many children actually achieve remission,” said Dr Chadwick.

“If even one child achieves remission, that would be considered a success. Today, newer more effective and better tolerated HIV medications are available for infants than when the study began, strengthening the prospect of limiting viral reservoirs and testing for possible remission in infants and children with HIV. Overall, this is an exciting advancement and an opportunity to change the course of pediatric HIV infection.”

The study was conducted in 11 countries – Brazil, Haiti, Kenya, Malawi, South Africa, Tanzania, Thailand, Uganda, USA, Zambia and Zimbabwe.

Source: Ann & Robert H. Lurie Children’s Hospital of Chicago

Categories : HIVTags :

In-depth: How do Long-acting HIV Treatments Work?

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Photo by Miguel Á. Padriñán

By Elri Voigt for Spotlight

Researchers have been trying to develop antiretroviral medicines that can last for weeks, months or even years per dose. It is thought that such long-acting therapies may eventually end up replacing the daily pills taken by most people living with HIV today.

As pointed out by Dr Anushka Naidoo, a Clinical Pharmacologist and Principal Investigator and Scientist at the Centre for AIDS Programme of Research in South Africa (CAPRISA), three such long-acting HIV medicines have made it to market so far. They are the injectables cabotegravir (CAB-LA) and rilpivirine (RPV-LA) and the dapivirine vaginal ring (DPV-VR). Of these only CAB-LA (two-monthly) and DPV-VR (monthly) have so far been approved by the South African Health Products Regulatory Authority (SAHPRA) for HIV prevention. CAB-LA and RPV-LA have been approved for HIV treatment in the United States, but not yet by SAHPRA.

Image: DOH

CAB-LA and DPV-VR are being rolled out as HIV pre-exposure prophylaxis (PrEP) in pilot studies in South Africa. Spotlight earlier this year provided an update on these pilots here.

How do long-acting formulations work?

Dr Sindiswa Maphumulo, a Specialist Virologist and lecturer at the University of the Free State, tells Spotlight that designing long-acting formulations is a very complex and costly process. She explains that when designing any drug, whether it is long-acting or not you need to look at two things – pharmacodynamics and pharmacokinetics. Basically, she says, pharmacokinetics refers to what the body does with the drug in question while pharmacodynamics refers to what the drug does to the body.

“So you’re going to have to know what is the human body going to do to this drug once you’ve administered it and also what is the drug targeting or aiming to do in the human body once it has been given,” she says. For long-acting drugs, studies need to determine what the half-life (how long it lasts in the body) of the drug is so the doses can be timed correctly. It is also essential that different populations are studied to determine how individual’s bodies react to the drug.

“You want to make sure that there is a steady release of that specific drug, which depends on the drug class that you’ve chosen because we target different sites of HIV [with different drug classes],” she adds.

Naidoo tells Spotlight that: “Long-acting drug delivery formulations enable slow drug release after administering a single dose over the course of days, weeks, months or even years, and can maintain a steady pharmacokinetics profile.”

Naidoo says that long-acting drugs are formulated so that they form a “depot” of the drug, either through the way the drug is released into the body or the way device that contains the drug is designed to slowly release it over time. Several ways of achieving this has been investigated, including long-acting injectables, implants, infusion pumps, and patches. Long-acting injections and implants, for example, are already widely used in South Africa as contraceptives.

For HIV this means that ARVs can either be stored in the body and slowly absorbed or be stored in a device that is placed in the body which releases consistent drug levels over time. For example, “long-acting injectables are usually the same medication that is taken in pill form but when injected they allow for the slow release of medication into the blood over a longer period of time,” says Naidoo.

How CAB-LA works

Maphumulo explains that CAB-LA and DPV-VR fall under different drug classes which target different stages of the HIV viral replication cycle inside the human body. Cabotegravir is an Integrase Strand Transfer Inhibitor (INSTI) – which is to say it targets the integrase enzyme that allow HIV to integrate itself into a cell’s DNA.

“Cabotegravir’s unique physiochemical and pharmacokinetic properties have permitted its formulation and delivery both as an oral tablet for daily administration and as a long-acting nanosuspension for monthly to quarterly intramuscular injection,” Naidoo says.

“Cabotegravir LA is made from the free acid form of cabotegravir, which has a low water solubility, a long systemic half-life and high antiviral potency,” says Emmanuella Chinonso Osuala, a Research fellow and PhD student based at CAPRISA.

She explains that the properties of this drug make it suitable for a so-called nanosuspension delivery system and allows for high levels of the drug be contained in a small volume that can be administered through an intramuscular injection. This is achieved by manufacturing cabotegravir, through a process called wet-bead milling, to form nanocrystals – approximately 200nm in size. These have a large surface which allows for “a slower and controlled release of the drug over time”.

“[The] drug is released from the injectable suspension over several months due to the slow dissolution of crystals from the suspension,” Osuala explains.

How DPV-VR works

Naidoo explains that DPV-VR is a ring made of “a flexible silicone polymer” and contains the drug dapivirine, which is slowly released over the course of a month and can be inserted and replaced by the women themselves each month. A three-month ring is also currently in development.

“The ring delivers dapivirine directly at the site of potential infection, with low systemic exposure (it acts at the site of action in the vagina and is not released in significant amounts into the blood circulation), which could minimise side effects…and reduce the risk of developing HIV (drug) resistance,” she says.

Dapivirine, according to Maphumulo is part of a drug class called Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), which block the reverse transcriptase enzyme on the HIV virus that allows for the transcription of HIV – which is an RNA virus into DNA. It is this transcription which would allow HIV to enter the human cell nucleus and replicate there.

Making current treatments long-acting

While long-acting forms of cabotegravir and dapivirine are clearly useful, these are far from the most widely used ARVs. Most HIV treatment in South Africa today is with a combination of three drugs, with the key one being dolutegravir. Earlier this year we reported on how more than 4.7 million people in the country have started or switched to dolutegravir-based HIV treatment in the last five years.

One group of researchers are trying to develop long-acting formulations of these commonly used ARVs. Using so-called drug combination nanoparticles (DcNP) they have developed a long-acting formulation of the ARVs tenofovir, lamivudine, and dolutegravir (LA-TLD) that shows some promise as a monthly injection. Early findings presented at this year’s International AIDS Society (IAS) conference in Australia and published in the journal AIDS suggest that the formulation achieves sufficient drug concentrations in non-human primates to allow for monthly dosing.

Dr Rodney Ho, an expert in biomedical science and pharmacology based at the University of Washington in the United States who led the research, tells Spotlight the study wanted to address a seemingly impossible question.

“Can we make three incompatible oral antivirals – tenofovir, lamivudine (which are water soluble) and dolutegravir (which is oil soluble and water-insoluble) – compatible and create a long-acting drug combination injectable product? With creativity and hard work, our team finally found a way to make this happen,” he says.

He explains that the three drugs were bound to lipid (fatty) nanoparticles using DcNP technology, which stabilises them so that the combination of drugs do not get released at the injection site immediately. Instead, the drugs are taken up by the body’s lymph and lymph nodes, which allows the drug to be metabolised within the body’s cells, which host the HIV virus, before it is taken up in the blood stream.

“As a result of this intentional design, LA-TLD has now provided data verifying that we are able to provide the necessary long-acting drug profile while achieving targeted drug exposure in cells and tissues of interest for an extended time,” Ho says.

“These results verified that a stable and scalable long-acting product, previously considered impossible, is now proven to be possible. This novel LA-TLD product can be administered via subcutaneous injection and will reach therapeutic drug levels within hours (not days which is needed for CABENUVA – LA-CAB and LA-RPV taken as HIV treatment). Thus, two-month oral leading doses may not be necessary,” he says.

Challenges around long-acting formulations

Osuala says there are several scientific challenges when it comes to long-acting formulations. This includes ensuring that: the drugs remain stable when released over long periods of time; sustained drug release is maintained; and the biocompatibility of the materials used in the product. Other challenges include issues around drug potency, as the amount of drug required for the formulation depends on its potency; as well as the cost and access to the formulations, as it is currently expensive to develop and manufacture which may hinder the accessibility of these products in low-and-middle-income (LMIC) countries.

Further challenges, according to Naidoo include the added complication that if adverse events occur for long-acting injectables, “one cannot simply stop taking the medication like one can with daily pills” since the drug will continue to be released into the body. One way to reduce this risk is through having an oral lead-in period where the drugs, like cabotegravir and rilpivirine that are set to be injected are first taken in pill form for four weeks, which can be stopped if an adverse event like hypersensitivity, an allergy or a severe side effect occurs.

Other challenges include the cold-chain storage requirements that some long-acting formulations and injections have, Naidoo says, “which can be challenging in LMIC settings so formulations without cold chain needs are needed.”

“The development of long-acting injectable formulations are a complex, time-consuming, and costly process. One of the challenges in the development of long-acting injectable formulations is the limited selection of ‘polymers’ and ’excipients’ (materials used to formulate the long-acting injectables that are available). As a result, some innovator companies develop proprietary excipients for use in long-acting injectable formulations, which can delay the development of generic long-acting injectable products,” she adds.

Republished from Spotlight under a Creative Commons Licence.

Source: Spotlight