Category: HIV

Categories : Cardiovascular Disease HIVTags :

Why a Major Finding on HIV and Statins may not be That Relevant in SA

On By ModernMedia
Photo by Miguel Á. Padriñán

By Elri Voigt

One of the biggest stories in HIV in the last year was that a class of medicines called statins could help reduce cardiovascular disease in people living with the virus. In response, treatment guidelines in the United States were quickly updated, but the picture is more complicated in South Africa. Spotlight’s Elri Voigt explores why the case for widespread use of statins by people living with HIV is less compelling in South Africa than in some other countries.

People living with HIV, provided they are stable on antiretroviral therapy, are affected by the same diseases as those who don’t have HIV, including cardiovascular disease, says Professor Mpiko Ntsekhe, head of Cardiology at Groote Schuur Hospital in Cape Town.

The key difference, he says, is that although both groups of people get the same spectrum of diseases, people living with HIV get those diseases more frequently and earlier. One way to think about this, he explains, is to imagine twins who are identical in every way except one is living with HIV. The twin living with HIV is more likely to get cardiovascular disease than the other twin.

And these differences can be substantial. Current evidence shows that people living with HIV have a twofold increased risk of developing cardiovascular disease compared to people not living with HIV, says Professor Hans Strijdom. He is the Head of the Division of Medical Physiology and Deputy Director of the Centre for Cardio-Metabolic Research in Africa (CARMA) at Stellenbosch University.  The cardiovascular risk attributable to HIV, Strijdom adds, is now believed to be equivalent to that posed by traditional risk factors such as smoking. This prompted an editorial in 2018 in one of the top cardiovascular journals, Circulation, advocating for HIV to be recognised as a major cardiovascular risk factor.

He explains that people living with HIV who are stable on treatment are living longer, making them susceptible to the normal risk posed by older age. They also have “modifiable risk factors, in other words lifestyle risk factors”, like a higher smoking and alcohol use incidence, as well as increasing rates of being overweight and obesity. Strijdom says that living with HIV, even when someone is stable on treatment, causes low-grade inflammation, which over time increases a person’s risk for cardiovascular disease. “That all in combination are the current theories [of] why we think that they have a bigger risk of cardiovascular disease,” he says.

Important study findings

Arguably, the biggest news from last year’s International AIDS Society (IAS) Conference in Australia was findings from a study on heart disease in people living with HIV. The trial, called REPRIEVE, showed that a class of cholesterol-busting drugs called statins can prevent a lot of cardiovascular disease events in people living with HIV whose cardiovascular disease (CVD) risk score meets a certain threshold. Spotlight previously reported on these findings, which showed that compared to placebo, daily treatment with 4mg oral pitavastatin – a specific statin – led to a 35% reduction in major adverse cardiovascular events (MACE) in people living with HIV classified to be at risk of cardiovascular disease.

When the findings were presented at the IAS conference, the study’s principal investigator, Dr Steven Grinspoon, said that while the researchers still have to assess more of the data collected to get a clearer picture of things, like the mechanisms driving cardiovascular disease across regions and conduct additional sub-group analyses, the study has already shown that using pitavastatin can save lives.

These sub-group analyses were discussed in greater detail at the Conference on Retroviruses and Opportunistic Infections (CROI) held in Denver in March this year. For the most part, the use of pitavastatin in the manner prescribed by REPRIEVE was considered a huge success, and the United States has since changed its guidelines to include the use of statins in the primary prevention of atherosclerotic cardiovascular disease.

Why it is different in South Africa

However, for low-and-middle-income countries like South Africa, the case for pitavastatin might not be as clear-cut. In fact, a panel discussion at CROI was dedicated to exploring the implications of the REPRIEVE findings for such countries.

Ntsekhe, who was a speaker on the CROI panel, tells Spotlight that data from REPRIEVE’s sub-group analyses reveal there was a striking difference in event rates – which in the case of the study are MACE in those who were getting the placebo – by country income status. He explains that as predicted in high-income countries, the event rates were high, while in low-and-middle income countries – particularly in Sub-Saharan Africa – event rates were very low.

He says one of the reasons for the difference in event rates was that the screening tool used in REPRIEVE worked well to identify those people living with HIV who might benefit from pitavastatin in high-income countries like the United States, but it did not work well in Sub-Saharan Africa.

This means using pitavastatin as part of a primary prevention strategy is a much more effective intervention in high-income countries than in low-and-middle income countries like in Sub-Saharan Africa because the cardiovascular disease profile is so different.

Ntsekhe explains the term cardiovascular disease itself is broad and all-encompassing and there are many forms, including valve disease, heart muscle disease, and vascular disease. The dominant form of cardiovascular disease in the high-income countries (which he refers to as the Global North) is known as atherosclerotic cardiovascular disease, which is characterised by a build-up of fatty deposits and plaque in the arteries.

In Sub-Saharan Africa though, Ntsekhe says “atherosclerotic cardiovascular disease is but one of many forms of cardiovascular disease”, taking the fourth or fifth place in the ranking of types of major heart disease.

Research conducted in high-income countries don’t always take differences in disease burden into account, according to Ntsekhe. This means that interventions researched in high-income countries and shown to be effective in that context won’t necessarily work as well in low-and-middle income countries like South Africa.

Strijdom concurs that while results from REPRIEVE in the global context were a game-changer, the findings are not easily transferable to South Africa’s context because pitavastatin is mainly aimed at reducing “bad cholesterol” and coronary artery disease (also called atherosclerosis).

‘Taking money away’

During the panel discussion at CROI, Ntsekhe asked whether Sub-Saharan Africa could justify taking money away from other health programmes that work in order to invest in pitavastatin.

“I said basically what should be a priority for us is a) finding tools that can better identify those at risk and b) continuing to focus on what our local data suggests are the priority areas,” Ntsekhe says.

“If your entire prevention strategy is aimed at atherosclerotic cardiovascular disease, but it isn’t the dominant cause of disease [in your country], you’re going to be treating a whole host of people to try and tackle this thing that affects very few in a sense,” he says.

“It was not anything about REPRIEVE, it was a wonderful study, the hypothesis was tested, and it was shown to be correct, the intervention we know works,” Ntsekhe says. “It really then comes down to regional areas to think very carefully about how best they’re going to get their biggest bang for their buck,” he says. “We have to carefully consider the local context, local burden, we have set local health priorities, and weigh benefit and cost before we adopt new interventions or recommendations.”

SA’s cardiovascular disease burden

While Strijdom says we don’t have great data, he points to a large systematic review and meta-analysis published in 2018 in Circulation, which estimates that around 15% of the total cardiovascular disease burden in South Africa is attributable to HIV. “It’s probably higher than that. I would say that probably about one in five people with heart disease have heart disease because of HIV in South Africa,” he says, adding “that figure is probably only going to increase”.

Because of this, he says, there is a need for proper and clear primary healthcare guidelines specifically aimed at managing cardiovascular disease in people living with HIV, which we don’t currently have.

Strijdom says what we have at the moment since the rollout of the 2019 National ART Clinical Guidelines is very basic guidelines. This involves screening someone who has just been diagnosed with HIV by taking their blood pressure, and testing urine for glucose and proteins, and an assessment of their general cardiovascular disease risk by taking their medical and family history. These guidelines, according to Strijdom, only make provision for routine screening at baseline, but screening guidelines at follow-up visits are insufficient.

“I am, however, aware of the fact that there is progress especially from the integrated chronic disease management model which is currently being piloted in South Africa – and hopefully with that will come much more definitive and universal guidelines,” he says. “The bottom line is that South Africa, in its public health [sector] especially, really very quickly needs to come up with very clear and more comprehensive guidelines to actively manage cardiovascular disease risk in people with HIV.”

Need for annual screening

Strijdom suggest that to improve screening for cardiovascular disease risk in people living with HIV, there needs to be annual screening of people’s weight, their measure of body fat based on height and weight, waist circumference, blood pressure, cholesterol and triglyceride levels as well as testing urine samples for kidney function. There also needs to be a thorough family and medical history conducted for each patient.

“It’s not really a very expensive or very exhaustive list of stuff that you have to do. Unless of course they have specific symptoms and signs that leads you in a specific direction that you then have to perhaps do an ECG [a test used to evaluate the functioning of the heart] or cardiac imaging but that is usually determined by what you get from their history and clinical examination,” he says.

Ntsekhe says public health strategies to combat the growing burden of non-communicable diseases (NCDs), including cardiovascular disease, in South Africa must be strengthened. These include screening and prevention tools like checking a patient’s blood pressure and blood glucose, advising against smoking and alcohol as well as promoting health lifestyle choices like exercise and weight loss. These interventions should be offered to everyone, regardless of whether they are living with HIV or not, he says.

“The thing about NCDs and cardiovascular disease, for the most part, they are diseases of lifestyle and behaviour. So, when you talk prevention, it’s not always about drug prevention,” he says. “It’s more about intensification of those [interventions] that are already in the public domain, are very effective, and cost very little. Many of the public health and primary healthcare guidelines do advise local ministries, local health authorities on what should be happening.”

In terms of public education, Stritjdom says people need to be aware that there is something like high blood pressure. “If people are aware they will come to the clinic and will say please measure my blood pressure,” he says.

“Our health system is understandably focused on infectious diseases, but if we are not careful, we will then be totally unprepared to tackle the epidemic that will have replaced it. Namely, cancer, heart disease, stroke, obesity, diabetes, and it will totally overwhelm our public healthcare system,” he says.

Republished from Spotlight under a Creative Commons licence.

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Categories : HIV Respiratory DiseasesTags :

What we can Learn about TB at the Autopsy Table

On By ModernMedia
Credit: Scientific Animations CC4.0

By Tiyese Jeranji for Spotlight

In addition to shedding light on what people actually die of, autopsies can also play an important role in helping us to better understand disease. Tiyese Jeranji unpacks tuberculosis-related autopsy research in the Western Cape and delves into some of the fascinating complexities of this branch of TB research.

Figuring out how many people in South Africa die every year of tuberculosis (TB) is not straight-forward. On the one hand, Stats SA’s frequent mortality reports put the number at under 30 000, on the other hand, the World Health Organization (WHO) estimates that it is over 50 000.

While this may at first glance seem like a large discrepancy, there is a simple explanation. The Stats SA figures are based on what is written on death notifications, and these notifications very often do not tell the full story of what a person died of. The WHO estimate, is derived using mathematical modelling that triangulates estimates based on several data sources.

Looking at the numbers from studies that determine the cause of death (or what people actually died of) is one of the ways we know that relying on death notifications result in an undercount of TB deaths. Such autopsy studies have consistently found that many people had undiagnosed TB at the time of death and that the undiagnosed TB was often the actual cause of death.

One review study published in the journal AIDS concluded that “in resource-limited settings, TB accounts for approximately 40% of facility-based HIV/AIDS-related adult deaths” and that “almost half of this disease remains undiagnosed at the time of death”. According to WHO figures, of the estimated 280 000 people who fell ill with TB in South Africa in 2022, over 65 000 were not diagnosed.

Importance of autopsy research

Dr Muhammad Osman, Academic Portfolio Lead and Senior Lecturer: Public Health at the University of Greenwich, tells Spotlight that it is important to do TB autopsy studies because it enables us to identify TB that was not diagnosed during life – and this helps us understand the true burden of the disease.

Osman says identifying TB at autopsies has significant benefits. He says by overlaying health seeking behaviour (how people visit clinics), we can identify missed opportunities for TB screening and design interventions to improve screening for TB. “We could trace family contacts of the deceased and offer TB screening and prevention. This is not taking place at present,” he says.

Osman and his colleagues published a paper in the International Journal of Infectious diseases in 2021  looking at TB in people with sudden unexpected death (SUD) in Cape Town. They found that active TB was identified at post-mortems in 6.2% of the 770 cases they studied. More strikingly, in around 92% of those cases the TB had not been diagnosed while the person was alive.

Osman says that these days there is an increasing awareness of undiagnosed and untreated TB. He points out that new interventions to improve TB testing and diagnosis have been implemented such as targeted universal testing — an approach by which people who do not have any TB symptoms, but who are considered to be at high risk of TB, are routinely offered TB tests.

He says these days healthcare worker risk is considered more carefully and he stresses the importance of protecting forensic and pathology teams. (Forensics focuses on determining the cause and manner of death while  pathology  is the study and diagnosis of disease through examination of tissue, cells, autopsies, and so on.)

Closing the gaps

Osman says their study also identified a gap between the pathology services and access to routine health service records. “We thought that this is an essential gap to close – the forensic/pathology services need access to routine health service. For a limited number of these deaths we were able to match their records to the public health clinic and hospital records – and many of them had contact with the health services in the six months before death,” he says.

“If forensic pathologists are given full access to the health records, they would know the timing of previous TB and the treatment outcomes of those episodes. The lung changes seen with TB are different in the case of active TB and healed/recovered TB. There are well documented macroscopic (what’s is seen by the examination) and microscopic (seen through histology and microbiology) findings,” says Osman.

A complex disease

The study of TB is complicated by the fact that TB can occur at several stages on a continuum and can impact several different parts of the body.

Professor Threnesan Naidoo, research pathologist at the African Health Research Institute (AHRI), tells Spotlight that when people think of TB, they usually think of the person who’s been coughing for a few months, loss of weight, loss of appetite, having night sweats, and maybe coughing up some blood. “But there’s a journey to that point and then generally beyond that point, and clinically, there’s a continuum of the disease. We refer to it as latent disease, subclinical, active and then healed TB,” he says. It is an area in which things are changing fast – a paper published in the Lancet medical journal last week proposed dividing TB into five stages.

Naidoo says autopsies provide an opportunity to study TB at different stages (latent, subclinical, active, healed) especially when someone with TB dies of another cause. He says they  can encounter people at any stage along the TB continuum because at any point someone could be shot, stabbed, or involved in a motor vehicle accident. “You (pathologist) have a unique opportunity to study the effect of TB on cells and tissue physically under a microscope and not through imaging (x-ray),” Naidoo says.

Autopsies also presents the opportunity to look at TB disease not only in the lung, but also the brain, thyroid gland, kidney or urinary system since TB has the capacity to spread everywhere, explains Naidoo.

“Autopsy gives you the opportunity to study TB everywhere,” he says. “Clinically (when someone is alive), you don’t  go about investigating the entire body. Neither is it practical nor feasible or safe. But [with an] autopsy you’re examining the entire body anyway. We study TB in totality,” he says.

How it is done

The standard manner of doing an autopsy involves a thorough examination of the body. Naidoo explains that the process starts with an external examination to document injuries, marks, and other physical characteristics that are visible. The internal examination involves dissecting organs, tissues, and body cavities to identify any abnormalities or signs of disease. Samples may be taken for further analysis, such as toxicology tests, histological examination, or TB research.

Any findings from the samples, Naidoo notes, must be interpreted taking into account changes that occur in a dead body. “[In] the living, you know, it’s a living person and they’re able to do things and you’re able to see things on imaging (X-Ray), but in the dead you have to account for the fact that the person has now demised and certain changes occur after death.”

Autopsy study at UCT

An ongoing study at the University of Cape Town is exploring the role of lymph nodes in the spread or containment of TB disease by looking at tissue of the deceased.

Much TB research so far have been done on animals and not on humans, points out Dr Virginie Rozot, research officer at the South African TB Vaccine Initiative (SATVI) and co-principal investigator of the UCT study. “We have great non-human primate and great mice studies that try to underline the mechanism of the  disease progression. However, animal models are not a true reflection of what happens in humans.

“For the longest time in these human studies, most studies have been done in the blood and what is happening in the blood has been taken to correlate with what is happening in the lung.”

In short, autopsies allow researchers to look directly at lung, brain and other tissue in a way that simply isn’t feasible in living people.

“So the only way you can actually access tissues is to do post mortem studies. Post mortem studies have been happening since the beginning of last century. And they were like fantastic studies, but the tools were not the same as we have today.  I think that should come back to the front of the scene of research because then you can ask all the questions we’ve been trying to answer on what is happening in the tissue by looking into the blood,” she says. “Autopsy allows us to study the exact part we want to study not just the blood.”

Collecting samples

In collaboration with the Western Cape Forensic Pathology Service, UCT has created  a postmortem sample collection platform to help with TB research. By leveraging the Inquest Act of 1959, which states that people that die of unnatural causes  must undergo a medico-legal investigation to determine the cause of death, Rozot and her team come in to conduct a post-mortem to get their samples. They aim to do the post-mortem in less than 24 hours after death.

Since starting this study about eight months ago, they have done 125 autopsies , with a consent rate of 64%. “I think our consent rate is incredible. We are still putting together our findings to determine how many cases of TB we have found so far by looking at autopsies,” says Rozot.

Representative samples

Dr Laura Taylor, forensic pathologist at the Western Cape Forensic Pathology Services, says the bodies that they look at, in line with the Inquest Act relating to unnatural deaths, are representative of people in South Africa. “However, they are not exactly representative of the entire South African population because there are certain socio economic groups that are more likely to die of unnatural deaths due to increased prevalence of trauma and violence in their communities,” she says.

Because there is no central database, Taylor couldn’t say how many cases of TB they find among the deceased. “[T]here are autopsy records or reports which are written for each case, but there is no central database for TB specifically detected [through] autopsy,” she says.

Forensic autopsy and other diseases

Rozot and Naidoo share the view that, if done well, TB autopsy studies can help shed light on other diseases.

The value of this information is that people dying with or from TB will also have any of  the other conditions such as hypertension, HIV, and diabetes, Naidoo says.

“You can work out all those variables… [people] don’t just come with diabetes, the diabetes changes the face of TB, HIV changes the face of TB and TB changes the face of those diseases as well. So, the complexity of it becomes something that we need to pay attention to, and look at all the common variables, like the association of TB and HIV is a big one. So studies might look at HIV infection and how it may affect TB and vice versa. Same with diabetes, hypertension, any of the other non-communicable diseases as well,” he concludes.

Republished from Spotlight under a Creative Commons licence.

Source: Spotlight

Categories : HIVTags :

Dramatic Decline in Condom Distribution in SA, New Figures Show

On By ModernMedia
Photo by Reproductive Health Supplies Coalition on Unsplash

By Catherine Tomlinson for Spotlight

Condom distribution in South Africa has dropped dramatically over the last five years, finds a Spotlight analysis of data recently published in the Health System Trust’s District Health Barometer.

The South African government distributed 45% fewer male condoms in 2022 than it did in 2018. The total number of male condoms distributed dropped by over 300 million from 728 million in the financial year from March 2018 to February 2019 to 403 million in 2022/2023. Female condom supply also declined over this period, but not as sharply.

The full extent of the actual decline in condom supply across the country over the past five years has not previously been reported. The Democratic Alliance, though, did raise the alarm bells about condom supply challenges in Gauteng in April 2023.

Provincial departments of health have pin-pointed the time required for certification of condoms by the South African Bureau of Standards (SABS) following the start of a new condoms tender in 2022 as a key driver of the decline, yet Health System Trust’s District Health Barometer (DHB) data shows that condom distribution figures have in fact steadily declined over the past five years. Similarly, while COVID-19-related supply chain interruptions were a contributing factor to supply shortages at the height of the pandemic, the decline in government supplied condoms started before the pandemic and continued after COVID-19 supply chain disruptions were resolved (as shown in the below graph).

The large decline in condom distribution in South Africa is alarming in the context of the country’s ongoing fight against HIV. While other biomedical interventions are now available to protect against HIV (such as HIV prevention pills), condoms should remain a cornerstone of countries’ HIV prevention strategies according to the World Health Organization.

Research conducted by the University of Witwatersrand’s Health Economics and Epidemiology Research Office (HE2RO) has found that condoms are not only the most cost-effective intervention available to government to combat HIV, but that provision of condoms is in fact cost saving for the country’s health system.

Where did condom distribution fall the most in 2022?

According to the DHB data, all provinces except for the Free State saw a decline in condom distribution in 2022/2023 compared with 2018/19 levels (as shown in the below graph).

The Eastern Cape distributed 65% fewer condoms in 2022/23 than it did in 2018/19, Gauteng and the Northern Cape distributed around 60% fewer, Limpopo 52% fewer, and the Western Cape around 46% fewer. With a reduction of around 19% over the five years, the decrease was much less pronounced in KwaZulu-Natal than in South Africa’s other provinces with large populations.

Male condoms distributed by province

Province2018/192019/202020/212021/222022/23
Eastern Cape73 672 41678 817 15751 122 50945 839 58825 490 700
Free State50 756 15053 246 00052 248 00055 352 80052 469 700
Gauteng172 953 486135 857 486146 303 254129 075 30369 220 678
KwaZulu-Natal111 028 599108 503 92096 529 200106 967 00089 664 600
Limpopo82 563 32267 818 20053 325 90052 862 90038 910 442
Mpumalanga67 150 60051 749 40038 316 00031 364 06635 627 000
Northern Cape13 934 96012 959 40010 825 9299 518 0005 194 000
North West50 820 28355 579 92139 841 97142 361 09730 810 803
Western Cape103 322 80082 055 96053 632 22672 031 60055 420 700
*This table shows a breakdown of male condoms distributed by province, according to data from the Health Systems Trust’s District Health Barometer.

What caused the decline in condom supply?

Condoms are tendered nationally by the National Department of Health for a three-year period. Condoms procured by government must be tested and certified by the SABS before distribution.

Neither the National Department of Health, nor the Gauteng Department of Health responded to questions from Spotlight about the reasons for the decline in condom distribution. However, Gauteng’s Department of Health has previously pinpointed SABS certification processes as the culprit for condom supply shortages in the province. According to an April 2023 media statement by the Gauteng Department of Health, suppliers that received tenders to supply condoms to the public sector were unable to supply condoms to the province while awaiting SABS certification in 2022 – resulting in low condom stock in the province.

Spokesperson for the Eastern Cape Health Department, Sizwe Kupelo, told Spotlight in response to questions for this article that in 2022/23 “for most of the year there were no condoms to distribute”.

Kupelo said that the decline in condom distribution in the Eastern Cape was due to a combination of lags in supply availability while condom suppliers were awaiting SABS certification and challenges in delivering condoms to distribution sites in the province.

“2022/23 was the end of the condom supply contract and the period to award a new contract effective from 1st April 2022. This transition experienced a delay in availing the condoms due the SABS quality assurance process that could be finalised only around September 2022,” said Kupelo, adding that the province started to receive condoms from October of the same year.

“The second reason were related to suppliers who were not finding it easy to deliver to Eastern Cape areas due to the high cost of transportation to the identified 26 delivery distribution sites across the province. Suppliers are all based in Gauteng,” said Kupelo.  This matter he said was now resolved.

Kupelo added that condom supply in the province is now improving. He said that the province had reached 96.7% of its target to distribute 17 million condoms in quarter 3 of 2023/24 (quarter 3 of 2023/24 is September to November 2023).

The SABS’ response

Lungelo Ntobongwana, acting CEO of the SABS, told Spotlight that all condoms that are distributed nationally by the Department of Health are tested at the SABS condom laboratory in Groenkloof, Pretoria. “The laboratory is an accredited and dedicated laboratory for the testing of condoms,” he said.

“Downtime or challenges to operations as a result of unplanned disruptions have been experienced on rare occasions and the SABS has incorporated contingency plans to ensure that the testing processes and deliverables would not be negatively impacted.

“The value chain, from the production of condoms to the distribution and usage of condoms, requires the intervention of various role players. When there is a shortage of condoms, it could be due to several reasons and chinks in the value chain.  The SABS can categorically state that there are currently no challenges in its laboratory or deliverables regarding the testing of samples,” said Ntobongwana.

Did clinics run out of condoms in 2022/23?

The National Department of Health insisted in April 2023 that while Gauteng was facing low stocks of condoms, there were no serious condom shortages in the country.

Surveys conducted by community-lead clinic monitoring group Ritshidze also show that condoms remained available in most facilities – but not all – throughout the year, but also indicate a pattern of rationing by health care workers and clinics. In some cases, they say condoms are only available in public clinics on request, and key populations often face stigma and discrimination when seeking to access condoms and lubricant.

Surveys conducted by Ritshidze in 2022, found that only 55% of sex workers could get enough condoms at public facilities. Ritshidze recommends that “condoms and lubricants should be available at all facilities and can easily be placed in the toilets or other areas of the clinic where people could take them without the fear of being seen and judged by others, or being told to put some back”.

Anele Yawa, General Secretary of the Treatment Action Campaign (a member of Ritshidze), told Spotlight that the organisation faced challenges in accessing adequate condoms for its community outreach efforts. He said when TAC undertakes community outreach efforts, its members request condoms from public health facilities for distribution in communities but are sometimes told that there are not enough condoms for this.

Yawa added that people seeking condoms from public clinics are often told they can only take a limited number of condoms because of stock availability and that in some clinics “the condom box is empty, there are no condoms”.

Has the decline in condom availability impacted condom usage?

There are some concerning indicators that condom usage in the country is declining, which may in part be related to the drastic decline in condom supply.

The Human Science Research Council (HSRC), which conducts regular surveys of HIV knowledge and sexual behaviour in South Africa, recently released early data from its 2022 survey. The survey showed that teenagers and young adults between 15 and 24 years old reported lower rates of condom use at last sex than in previous survey years. The data presented did not pin-point a cause for the decline – apart from supply constraints, other factors like a decrease in people’s perceived risk of contracting and dying of HIV may also play a role.

The HSRC will release its full survey results in April 2024, which are expected to provide more insight into why condom use at last sex declined among 15- to 24-year-olds in 2022.

Another concerning indicator of declining condom usage is the reported rise in sexually transmitted infections (STIs) in Gauteng.  Spotlight reported in February that the worried resurgence in reported cases of STIs in Gauteng in 2023 is a wake-up call that control and management strategies are not keeping pace with the growing disease burden in South Africa’s most populous province.

In response to the increase in STIs, Gauteng’s Health MEC Nomantu Nkomo-Ralehoko recommended expanded, consistent condom use – noting a number of factors including non-use of condoms, inconsistent use of condoms, and the forgoing of condoms by people using Pre-Exposure Prophylaxis (PrEP) as contributors to the rise in STIs. PrEP refers to antiretrovirals taken to prevent HIV infection.

Dismissing the conclusion of a causal relationship between a higher number of people being initiated on PrEP and the higher recorded number of STIs, Professor Linda-Gail Bekker, director of the Desmond Tutu Health Foundation, told Spotlight that there is no evidence to back up the claim that PrEP is leading to lower rates of condom usage. She added that the increase in STI diagnoses may be attributed to increased rates of testing, which has increased in the PrEP era.

“The notion that sexually transmitted infections have suddenly increased in the era of PrEP does not have evidence to support this,” said Bekker, adding “we have no strong evidence to suggest that people are having more condomless sex than before”.

“The value of condoms as a measure against sexually transmitted infections as well as unwanted pregnancy is not disputed and condoms remain the corner stone of the HIV response” said Bekker. “However, we know that for many people, and particularly young women and young men who have sex with men, the choice to use male condoms is not always a given and negotiating condom use may not be easy and can be dangerous,” she said.

Republished from Spotlight under a Creative Commons licence.

Source: Spotlight

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

On By ModernMedia
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

On By ModernMedia
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

On By ModernMedia
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