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.
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.”
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.
“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.
Dr Vuyiseka Dubula-Majola, the former General Secretary of the Treatment Action Campaign, reflects on her journey and new role at the Global Fund. PHOTO: Joyrene Kramer
By Biénne Huisman for Spotlight
Dressed in a dark jacket, rain is pelting Vuyiseka Dubula-Majola’s face as she rushes past bare trees in Geneva, Switzerland. Along with her two children, Dubula-Majola has newly moved into a house in nearby Genthod, from where she commutes to work by train.
In October, the Global Fund to Fight AIDS, Tuberculosis [TB] and Malaria, appointed Dubula-Majola as head of their community, rights and gender department. The Global Fund has allocated tens of billions of dollars around the world to fight HIV since its inception in 2002.
Five weeks into the job, Dubula-Majola tells Spotlight that a big challenge for her will be to hone a new tool – that of diplomacy.
Laughing, the former General Secretary of the Treatment Action Campaign (TAC) says that in the past, diplomacy has not been her greatest strength.
“In this new job, I am required to be diplomatic,” she says. “Basically, diplomacy is being nice in the face of atrocities, and I am not that person. So it will be a huge challenge for me, it’s going to take a shift. I will have to keep asking myself, ‘what value I can add in this position?’ While developing new tools and new ways of fighting, without being the noisy person in the room.”
The power of collective action
Known for not mincing her words, the activist-scholar is talking to Spotlight over Zoom while walking to the Global Fund’s offices in central Geneva. She adds: “Activists don’t like bureaucracies by nature, but you have a voice here. You have political currency to shift things. It’s a tough one, but I’m there.”
In a 2014 TedX talk hosted in London, an inflamed Dubula-Majola told the audience that she is angry – angry with her father, angry with her government, angry at everyone. But that she was using her anger to fuel her work.
Vuyiseka Dubula-Majola was recently appointed at head of the Global Fund’s community, rights and gender department. PHOTO: Supplied
While she is in Switzerland, Dubula-Majola’s heart still brims with African proverbs, such as: “When spider webs unite, they can tie up a lion.” She has experienced the power of such collective action first-hand at the TAC, but now she’ll be applying it on a different stage. Indeed, her new job is “to ensure that the Global Fund strongly engages civil society and promotes human rights and gender equality”, with a particular focus on supporting community led organisations.
As a role model for her new diplomatic duties, Dubula-Majola cites American public health official Loyce Pace. “Loyce Pace who runs the health program in the United States government, she is very effective in what she does while hardly saying anything in public. But she is shifting norms – bringing priority to black and poor people. She uses her allies and many other people similar to her to say things louder than she could…I guess this is another step of growth in my activist journey – to still be as effective, as radical, the very same eagerness and passion, but silently.”
‘There was no time to dream’
Dubla-Majola grew up in a village near Dutywa in the Eastern Cape. Aged 22 in Cape Town in 2001, she spiralled with depression after being diagnosed with HIV. But instead of resigning herself to what was then still a death sentence for most people, she joined the TAC – working night shifts at the McDonalds drive-through in Green Point, while by day she joined the fight to bring antiretrovirals and other medicines to South Africa.
“As a 22-year-old, I did not have fun, there was no time to dream,” she recalls. “I was fighting for my life and the lives of others. I never thought I would have children, I never thought I would get married, I never thought I would love again. Because there was also the issue of who infected me, how did this happen? You start resenting relationships.”
At the forefront of social justice activism for most of South Africa’s young democracy – a role model for people living with HIV, and for those fighting inequality – Dubula-Majola lead the TAC from 2007 to 2013, after which she joined Sonke Gender Justice as director of policy and accountability. She holds an MA in HIV/AIDS management from Stellenbosch University; her PhD from the University of KwaZulu-Natal examined “grassroots policy participation after a movement has succeeded to push for policy change,” using MSF’s [Médecins Sans Frontières] pioneering antiretroviral sites in Khayelitsha and Lusikisiki as samples.
‘Build and regain the dignity of poor people’
In 2018, when Stellenbosch University offered her a job as director of its Africa Centre for HIV/AIDS Management, Dubula-Majola was circumspect. Why take up appointment at a white male-dominated institution shackled by slow transformation, in an elitist town? But she took on the challenge to become the transformation she wanted to see.
Dubula-Majola tells Spotlight that while relishing the privilege of academia – a space to reflect – it saw her away from “the heat of the activist fire” for too long. Five years later, a new challenge awaits.
Reflecting on Stellenbosch, she says: “This [job at the Global Fund] is even harder, because it’s not just one country, one university. This is all the continents of the world. All of them facing the same thing, the struggle here is to build and regain the dignity of poor people around the globe.”
Despite her early misgivings about relationships, Dubula-Majola married fellow TAC activist, Mandla Majola. Their children, now aged 10 and 16, are HIV-negative. Presently Majola is helping with their friend Zackie Achmat’s independent campaign for the 2024 general elections, after which he will join his wife in Geneva. The family will unite in Switzerland for Christmas though – “which will be the most miserable and cold Christmas,” says Dubula-Majola, laughing. “It will be our first winter Christmas and our last. As we just arrived a month ago, it doesn’t make sense to travel back to South Africa for the holidays.”
Overall she says she remains hopeful, adding that movements like #MeTo are lessons in global solidarity.
Her thoughts on continuing the fight against HIV: “It is up to HIV positive people, and those who want to remain HIV negative, to steer towards an AIDS-free generation. We must stop complaining, thinking politicians will do everything for us, and do it ourselves.”
Meanwhile, Global Fund representatives have voiced confidence in Dubula-Majola’s ability to lead. Marijke Wijnroks, head of the organisation’s strategic investment and impact division, said in a statement: “Following an extensive search process, I am delighted to say that we found the ideal person for this role. As a person living with HIV, Vuyiseka’s lived experience and leadership style are well aligned to what we need from this critical role.”
Note: Dubula-Majola is a former General Secretary of the TAC. Spotlight is published by SECTION27 and the TAC, but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.
An unexpectedly high percentage of children, who were born with HIV and started treatment within 48 hours of life, exhibit biomarkers by two years of age that may make them eligible to test for medication-free remission, according to a multinational study published in The Lancet HIV.
“Moving away from reliance on daily antiretroviral therapy (ART) to control HIV would be a huge improvement to the quality of life of these children,” said Protocol Co-Chair and senior author Ellen Chadwick, MD, at Ann & Robert H. Lurie Children’s Hospital.
Conducted in 11 countries including South Africa, the proof-of-concept study was charged with replicating the case of HIV remission as seen in the “Mississippi baby” that was reported in 2013. In that case, the infant started ART at 30 hours of life, was treated for 18 months, and achieved 27 months of ART-free remission before the virus rebounded. Typically, if ART is stopped, the virus rebounds within a month.
The study included a three-drug ART regimen initiated within 48 hours of life, with the fourth drug added within 2-4 weeks. This is very early treatment compared to the standard of care where three-drug ART may not begin until 2-3 months of age.
In the US, however, based on earlier findings from this study, very early treatment is now the norm for infants at high risk of acquiring HIV infection from their mother.
“With earlier treatment, we hope to limit or prevent the establishment of viral reservoirs in the body. These viral reservoirs hold small amounts of hidden virus which are hard to reach with ART. By shrinking these reservoirs, we expect to increase the amount of time that patients can be in remission, without needing daily ART,” said co-author and Protocol Co-Chair Jennifer Jao, MD, MPH, from Lurie Children’s.
Dr Chadwick adds: “Another benefit of smaller viral reservoirs might be that newer treatments such as long-acting antibody therapies or therapeutic vaccines could potentially be used instead of daily ART.”
“Our results show a higher percentage of children might be eligible to interrupt therapy than we expected, and the next step is to stop ART and see how many children actually achieve remission,” said Dr Chadwick.
“If even one child achieves remission, that would be considered a success. Today, newer more effective and better tolerated HIV medications are available for infants than when the study began, strengthening the prospect of limiting viral reservoirs and testing for possible remission in infants and children with HIV. Overall, this is an exciting advancement and an opportunity to change the course of pediatric HIV infection.”
The study was conducted in 11 countries – Brazil, Haiti, Kenya, Malawi, South Africa, Tanzania, Thailand, Uganda, USA, Zambia and Zimbabwe.
Researchers have been trying to develop antiretroviral medicines that can last for weeks, months or even years per dose. It is thought that such long-acting therapies may eventually end up replacing the daily pills taken by most people living with HIV today.
As pointed out by Dr Anushka Naidoo, a Clinical Pharmacologist and Principal Investigator and Scientist at the Centre for AIDS Programme of Research in South Africa (CAPRISA), three such long-acting HIV medicines have made it to market so far. They are the injectables cabotegravir (CAB-LA) and rilpivirine (RPV-LA) and the dapivirine vaginal ring (DPV-VR). Of these only CAB-LA (two-monthly) and DPV-VR (monthly) have so far been approved by the South African Health Products Regulatory Authority (SAHPRA) for HIV prevention. CAB-LA and RPV-LA have been approved for HIV treatment in the United States, but not yet by SAHPRA.
Image: DOH
CAB-LA and DPV-VR are being rolled out as HIV pre-exposure prophylaxis (PrEP) in pilot studies in South Africa. Spotlight earlier this year provided an update on these pilots here.
How do long-acting formulations work?
Dr Sindiswa Maphumulo, a Specialist Virologist and lecturer at the University of the Free State, tells Spotlight that designing long-acting formulations is a very complex and costly process. She explains that when designing any drug, whether it is long-acting or not you need to look at two things – pharmacodynamics and pharmacokinetics. Basically, she says, pharmacokinetics refers to what the body does with the drug in question while pharmacodynamics refers to what the drug does to the body.
“So you’re going to have to know what is the human body going to do to this drug once you’ve administered it and also what is the drug targeting or aiming to do in the human body once it has been given,” she says. For long-acting drugs, studies need to determine what the half-life (how long it lasts in the body) of the drug is so the doses can be timed correctly. It is also essential that different populations are studied to determine how individual’s bodies react to the drug.
“You want to make sure that there is a steady release of that specific drug, which depends on the drug class that you’ve chosen because we target different sites of HIV [with different drug classes],” she adds.
Naidoo tells Spotlight that: “Long-acting drug delivery formulations enable slow drug release after administering a single dose over the course of days, weeks, months or even years, and can maintain a steady pharmacokinetics profile.”
Naidoo says that long-acting drugs are formulated so that they form a “depot” of the drug, either through the way the drug is released into the body or the way device that contains the drug is designed to slowly release it over time. Several ways of achieving this has been investigated, including long-acting injectables, implants, infusion pumps, and patches. Long-acting injections and implants, for example, are already widely used in South Africa as contraceptives.
For HIV this means that ARVs can either be stored in the body and slowly absorbed or be stored in a device that is placed in the body which releases consistent drug levels over time. For example, “long-acting injectables are usually the same medication that is taken in pill form but when injected they allow for the slow release of medication into the blood over a longer period of time,” says Naidoo.
How CAB-LA works
Maphumulo explains that CAB-LA and DPV-VR fall under different drug classes which target different stages of the HIV viral replication cycle inside the human body. Cabotegravir is an Integrase Strand Transfer Inhibitor (INSTI) – which is to say it targets the integrase enzyme that allow HIV to integrate itself into a cell’s DNA.
“Cabotegravir’s unique physiochemical and pharmacokinetic properties have permitted its formulation and delivery both as an oral tablet for daily administration and as a long-acting nanosuspension for monthly to quarterly intramuscular injection,” Naidoo says.
“Cabotegravir LA is made from the free acid form of cabotegravir, which has a low water solubility, a long systemic half-life and high antiviral potency,” says Emmanuella Chinonso Osuala, a Research fellow and PhD student based at CAPRISA.
She explains that the properties of this drug make it suitable for a so-called nanosuspension delivery system and allows for high levels of the drug be contained in a small volume that can be administered through an intramuscular injection. This is achieved by manufacturing cabotegravir, through a process called wet-bead milling, to form nanocrystals – approximately 200nm in size. These have a large surface which allows for “a slower and controlled release of the drug over time”.
“[The] drug is released from the injectable suspension over several months due to the slow dissolution of crystals from the suspension,” Osuala explains.
How DPV-VR works
Naidoo explains that DPV-VR is a ring made of “a flexible silicone polymer” and contains the drug dapivirine, which is slowly released over the course of a month and can be inserted and replaced by the women themselves each month. A three-month ring is also currently in development.
“The ring delivers dapivirine directly at the site of potential infection, with low systemic exposure (it acts at the site of action in the vagina and is not released in significant amounts into the blood circulation), which could minimise side effects…and reduce the risk of developing HIV (drug) resistance,” she says.
Dapivirine, according to Maphumulo is part of a drug class called Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), which block the reverse transcriptase enzyme on the HIV virus that allows for the transcription of HIV – which is an RNA virus into DNA. It is this transcription which would allow HIV to enter the human cell nucleus and replicate there.
Making current treatments long-acting
While long-acting forms of cabotegravir and dapivirine are clearly useful, these are far from the most widely used ARVs. Most HIV treatment in South Africa today is with a combination of three drugs, with the key one being dolutegravir. Earlier this year we reported on how more than 4.7 million people in the country have started or switched to dolutegravir-based HIV treatment in the last five years.
One group of researchers are trying to develop long-acting formulations of these commonly used ARVs. Using so-called drug combination nanoparticles (DcNP) they have developed a long-acting formulation of the ARVs tenofovir, lamivudine, and dolutegravir (LA-TLD) that shows some promise as a monthly injection. Early findings presented at this year’s International AIDS Society (IAS) conference in Australia and published in the journal AIDS suggest that the formulation achieves sufficient drug concentrations in non-human primates to allow for monthly dosing.
Dr Rodney Ho, an expert in biomedical science and pharmacology based at the University of Washington in the United States who led the research, tells Spotlight the study wanted to address a seemingly impossible question.
“Can we make three incompatible oral antivirals – tenofovir, lamivudine (which are water soluble) and dolutegravir (which is oil soluble and water-insoluble) – compatible and create a long-acting drug combination injectable product? With creativity and hard work, our team finally found a way to make this happen,” he says.
He explains that the three drugs were bound to lipid (fatty) nanoparticles using DcNP technology, which stabilises them so that the combination of drugs do not get released at the injection site immediately. Instead, the drugs are taken up by the body’s lymph and lymph nodes, which allows the drug to be metabolised within the body’s cells, which host the HIV virus, before it is taken up in the blood stream.
“As a result of this intentional design, LA-TLD has now provided data verifying that we are able to provide the necessary long-acting drug profile while achieving targeted drug exposure in cells and tissues of interest for an extended time,” Ho says.
“These results verified that a stable and scalable long-acting product, previously considered impossible, is now proven to be possible. This novel LA-TLD product can be administered via subcutaneous injection and will reach therapeutic drug levels within hours (not days which is needed for CABENUVA – LA-CAB and LA-RPV taken as HIV treatment). Thus, two-month oral leading doses may not be necessary,” he says.
Challenges around long-acting formulations
Osuala says there are several scientific challenges when it comes to long-acting formulations. This includes ensuring that: the drugs remain stable when released over long periods of time; sustained drug release is maintained; and the biocompatibility of the materials used in the product. Other challenges include issues around drug potency, as the amount of drug required for the formulation depends on its potency; as well as the cost and access to the formulations, as it is currently expensive to develop and manufacture which may hinder the accessibility of these products in low-and-middle-income (LMIC) countries.
Further challenges, according to Naidoo include the added complication that if adverse events occur for long-acting injectables, “one cannot simply stop taking the medication like one can with daily pills” since the drug will continue to be released into the body. One way to reduce this risk is through having an oral lead-in period where the drugs, like cabotegravir and rilpivirine that are set to be injected are first taken in pill form for four weeks, which can be stopped if an adverse event like hypersensitivity, an allergy or a severe side effect occurs.
Other challenges include the cold-chain storage requirements that some long-acting formulations and injections have, Naidoo says, “which can be challenging in LMIC settings so formulations without cold chain needs are needed.”
“The development of long-acting injectable formulations are a complex, time-consuming, and costly process. One of the challenges in the development of long-acting injectable formulations is the limited selection of ‘polymers’ and ’excipients’ (materials used to formulate the long-acting injectables that are available). As a result, some innovator companies develop proprietary excipients for use in long-acting injectable formulations, which can delay the development of generic long-acting injectable products,” she adds.
Newly announced results of a pivotal phase 3 trial have demonstrated the effectiveness of a new one-dose treatment for gonorrhoea. The medicine, called zoliflodacin, is the first new drug developed to treat gonorrhoea in over 30 years. More than half of the 930 patients included in the trial were from South Africa, including women, adolescents, and people living with HIV.
Zoliflodacin, which was shown to be non-inferior to (as good as) the currently used treatment in treating uncomplicated gonorrhoea, provides an important new tool to combat rising rates of drug resistant gonorrhoea. It was found to be generally well tolerated and there were no serious adverse events or deaths recorded in the trial. So far, only top line results have been shared in a media release and the findings have not yet been published in a medical journal. (You can see some technical details of the study design on ClinicalTrials.gov)
The World Health Organization raised the alarm about increasing rates of drug resistant gonorrhoea in 2017, noting the emergence of cases of untreatable gonorrhoea resistant to all available antibiotics. According to the United States Centers for Disease Control and Prevention “medication to treat gonorrhoea has been around for decades, but the bacteria has grown resistant to nearly every drug ever used to treat it”. They say: “only one class of antibiotics known as cephalosporins remains to treat the infection”.
As a drug from a new class of antibiotics, zoliflodacin, offers a new potential treatment for patients whose gonorrhoea was previously untreatable, as well as a new tool for safeguarding the ongoing effectiveness of currently available antibiotics.
How zoliflodacin may change gonorrhoea treatment
Professor Sinead Delany-Moretlwe, Director of Research for Wits RHI and the National Principal Investigator for the trial in South Africa, told Spotlight that while zoliflodacin may be used to treat drug resistant gonorrhoea, it also provides an attractive new treatment option for first-line treatment of gonorrhoea in some countries (in other words, gonorrhoea that is not resistant to other treatments).
Zoliflodacin, which is taken as a single oral dose, is simpler to administer than the current standard of care, which involves a combination of injectable ceftriaxone and oral azithromycin. Removing the need for an injection could simplify the administration of gonorrhoea treatment and improve its uptake.
Using zoliflodacin as first-line gonorrhoea treatment can also help safeguard the ongoing effectiveness of cephalosporins (including ceftriaxone), according to Delany-Moretlwe, which she adds are needed not just for treatment of gonorrhoea, but also other infections.
According to Delany-Moretlwe, because zoliflodacin is the first of a new class of antibiotics with novel mechanisms of action and without existing cross resistance, the hope is that widespread use of zoliflodacin as first-line gonorrhoea treatment will slow the emergence of resistance compared with the medicines currently being used.
The Global Antibiotic Research and Development Partnership (GARDP), a non-profit that sponsored the trial, points out that: “Antimicrobial resistance [AMR] has been around for millions of years, long before the first man-made antibiotics. So, drug-resistant bacteria are inevitable and will eventually affect all antibiotics”. They state: “to beat AMR we need a steady supply of new antibiotics to be developed that are effective against drug-resistant bacteria, particularly for priority pathogens that have the greatest public health impact.”
Gonorrhoea in South Africa
South Africa has incredibly high rates of gonorrhoea, with an estimated 2 million new cases annually. While data on rates of drug resistance in the country is limited, the data that is available indicates that ceftriaxone resistance in the country is low, but azithromycin resistance is concerningly high in some parts of the country.
As there is no routine screening for gonorrhoea in South Africa, linkage to treatment remains a challenge. Currently, diagnosis is largely done through symptomatic reporting by patients. But this approach misses many cases as some patients do not self-report symptoms and some cases of gonorrhoea are asymptomatic.
In 2022, the Southern African HIV Clinicians Society released new guidelines for the management of sexually transmitted infections which called for provider-initiated symptomatic screening and provider-initiated diagnostic screening in high-risk populations.
The country’s new National Strategic Plan on HIV, TB and STIs has set a target to increase the number of pregnant women tested for gonorrhoea from 10% in 2023 to 80% by 2028 and has committed to implementing diagnostic testing in other priority populations, including adolescent girls and young women.
How will new gonorrhoea treatments be commercialised?
Zoliflodacin was developed by GARDP in collaboration with the company Innoviva Specialty Therapeutics. According to GARDP, it holds the rights to register and commercialise zoliflodacin in more than three-quarters of the world’s countries, including all low-income countries, most middle-income countries, and several high-income countries. While, Entasis Therapeutics Limited, an affiliate of Innoviva Specialty Therapeutics, “retains the commercial rights for zoliflodacin in the major markets in North America, Europe, Asia-Pacific, and Latin America”.
South Africa is one of the countries in which GARDP holds the rights to register and commercialise zoliflodacin. It is anticipated that this will be done through selection and licensing of companies to manufacture and supply zoliflodacin in South Africa and other countries where GARDP holds commercialisation rights.
GARDP recently launched a request for proposals from partners that are interested in commercialising zoliflodacin. GARDP has also signed a memorandum of understanding with two generic producers to explore opportunities to commercialise the medicine in low-and-middle-income countries.
While the price that will be offered by commercial partners for the product remains to be seen, it is anticipated that products will be made available at affordable prices in line with GARDP’s goal to ensure that “all GARDP products are available, affordable, and appropriately used across populations that need them”.
“This is the first study to address a World Health Organization priority pathogen that has been sponsored and led by a non-profit organization,” says GARDP.
“This demonstrates that GARDP’s model can play a crucial role in helping to fix the public health failure at the heart of the global AMR crisis,” says Professor Glenda Gray, GARDP board member and President of the South African Medical Research Council.
SA involvement
According to GARDP, South Africa had the highest number of participants in the global trial, across six sites in four provinces: Wits RHI in Hillbrow, Johannesburg; the Desmond Tutu HIV Foundation in Masiphumelele, Cape Town; Setshaba Research Centre in Soshanguve, Gauteng; the SAMRC’s clinical research sites in Botha’s Hill and Tongaat in KwaZulu-Natal; and Ndlovu Research Centre in Groblersdal, Limpopo.
“We have also been able to leverage our HIV experience to build capacity for trials of novel STI technologies, a previously neglected area. Undertaking this vital work on a new treatment for gonorrhoea has also given us the opportunity to focus sharply on the local situation in South Africa,” says Delany-Moretlwe.
A new injectable solution that self-assembles into a gel under the right conditions could help manage HIV unlike any currently available methods, researchers report in the Journal of the American Chemical Society. Developed by John Hopkins University researchers, the new gel releases a steady dose of the antiretroviral lamivudine over six weeks, suggesting people living with HIV could have an alternative to the daily pill regimen.
“The primary challenge in HIV treatment is the need for lifelong management of the virus, and one way to address this is to reduce dosing frequencies to help patients stick to medical regimens,” said lead researcher Honggang Cui, a chemical and biomolecular engineer. “This new molecular design shows us a future in which drug hydrogelation can do that to improve HIV treatment.”
In plasma-like conditions, Cui’s team showed the gel quickly separates into molecules of lamivudine. By injecting the gel in the backs of mice, the researchers found one injection was sufficient to maintain effective and lasting drug concentrations for 42 days with nearly no side effects.
“Our goal is to help improve people’s quality of life,” Cui said. “The antiviral substance can be injected under the skin and remain in place over an extended period, releasing the therapeutic compound slowly and consistently – a critical need for individuals with HIV.”
For people living with HIV, the key is maintaining bloodstream drug levels at concentrations that suppress virus load in the body. But that can be difficult with traditional approaches because the body naturally rids itself of these chemicals, Cui said, which is why different treatments require different dosages and dosing frequencies to work.
Most antiretroviral therapies use a combination of drugs, so the researchers plan to include other drugs in tests. Because lamivudine is an FDA-approved drug to treat HIV and hepatitis B, the researchers said the hydrogel could also help manage hepatitis B.
“This is a novel way to deliver anti-HIV meds, and this platform has the advantage that a single polymer can be programmed to deliver several different drugs simultaneously,” said co-author Charles W. Flexner, a professor of medicine, pharmacology, and molecular sciences in the Johns Hopkins School of Medicine. “One of the drawbacks of the approved injectable HIV treatments is that none have activity against hepatitis B virus, which is a common co-infection with HIV, especially in Asia and Africa. This formulation delivers lamivudine, a drug active against both HIV and HBV, but can also be modified to deliver tenofovir, which is the current standard of care for HBV treatment.”
The team envisions their hydrogel working as a preventive measure, similar to how some people take anti-HIV drugs to avoid infection.
“Keeping the high drug levels in plasma for 42 days is very impressive,” Cui said. “But in the future, we hope it will be even longer.”
Hydrogels have unique water-absorbing properties that give them a jellylike consistency resembling biological tissue. The new gel undergoes self-formulation, stays close to the site of injection, and separates into molecules that can fend off the virus without the need for additional carriers or delivery materials.
“The most exciting aspect of these gel filaments is that they consist entirely of the therapeutic agent itself,” Cui said. “Everything originates from the same compound after injection, and this simplest drug formulation could streamline the regulatory approval process once clinical efficacy is demonstrated.”
The team tweaked the molecular properties of lamivudine to act as the building blocks of a supramolecular polymer, a large chain of repeating molecules that can either stick together tightly or come apart, depending on temperature, pH, and other external conditions.
The percentage of people living with HIV receiving a three to six-month supply of ARVs at a time in the Free State has dropped from 13% last year to 3% this year, making the province the worst performer in multi-month dispensing of ARVs in the country. This while in Mpumalanga, 64% of people living with HIV receive a three to six-month refill as per national guidelines.
This is according to the latest figures from community-led clinic monitoring group, Ritshidze. In its third Free State report, released on 30 August, the group notes several challenges faced by people living with HIV, key populations that include men who have sex with men and sex workers, among others, and other public healthcare users in the province. Among these are a lack of multi-month dispensing of ARVs and long waiting times at clinics, two factors that can make it harder to take treatment as prescribed.
The report notes that multi-month dispensing often allows people living with HIV to collect their treatment at pick-up points situated at healthcare facilities or externally in the community, making it quicker and easier to collect ARVs. Yet the monitoring data shows that 41% of people using facility pick-up points said they still have to collect files, take vitals, and see a clinician before getting their parcel, which adds to unnecessary delays. “Overall, these shortcomings contribute to slow progress towards getting everyone to start and stay on HIV treatment,” the report states.
Monitoring for the new report was done in April and May this year at 21 facilities and included interviews with 1 095 public healthcare users across four districts in the province. Of the public healthcare users interviewed, 47% (516) were people living with HIV (PLHIV) and 16% (180) were younger than 25.
The recommendations
The report stresses that multi-month dispensing of antiretroviral treatment is just one of several ways to help reduce the burden on the healthcare system, and to reduce the pressure manifesting in long waiting times, overcrowded clinics, and overworked clinic staff. Ritshidze recommends – as it did in its two previous Free State reports – that “the department extends and implements refills up to three months by end of December 2023, and six months by end of September 2024”. It is also recommended that the department, “Ensures that all people living with HIV are offered a range of repeat prescription collection strategy options”, “that facility pick-up points are one-stop very quick ART collection-only, that clinic visits are under 30 minutes and there is no need to go to the clinic registry, collect folders, and to see a clinician.
“Multi-month dispensing and repeat prescription collection strategies can simplify and adapt HIV services across the cascade in ways that both serve the needs of people living with HIV better and reduce unnecessary burdens on the health system,” the report notes.
As people living with HIV often report that healthcare workers send them to the back of the queue when they miss appointments, Ritshidze recommends that staff acknowledge and understand the importance of ART continuity, that it is normal to miss appointments, and that no person living with HIV should be sent to the back of the queue if they miss an appointment as per the welcome back campaign strategy. Ritshidze also recommends that clinics must not require transfer letters to restart or continue with ART and any reports where treatment is delayed by healthcare workers requiring a transfer letter should be urgently investigated and disciplinary action taken where appropriate.
The value of multi-month dispensing
The value of multi-month dispensing is well established. Study findings on the HIV programme in Ethiopia released in May this year, for example, stressed that multi-month dispensing of antiretroviral therapy is “an integral component of differentiated HIV service delivery for people living with HIV”. Ethiopia was the first African country to implement six-month dispensing at scale.
The benefits cited by study participants included “time and cost-savings, fewer work disruptions, reduced stigma due to fewer clinic visits, better medication adherence, and improved overall health”. The perceived health system-level benefits included “improved quality of care, decongested facilities, reduced provider workloads, and improved record-keeping”.
According to Clinical Director at the Southern African HIV Clinicians Society, Camilla Wattrus, requiring people to visit healthcare facilities monthly to collect routine medication, can place a huge strain on the available resources in these facilities.
“Multi-month dispensing for eligible, stable patients on chronic medications, including ARVs can help to alleviate some of this burden, easing up the staff’s available time towards those with acute conditions and unstable patients, says Wattrus.
She says multi-month dispensing is also one way to increase access for stable patients to their medication by reducing potential adherence barriers leading to poor health and loss of income due to transport costs and time away from work – all factors identified by Ritshidze through its monitoring. External pick-up points can also help alleviate congestion at facilities and reduce waiting times.
When asked what the Free State health department can do to improve its performance on multi-month dispensing, Wattrus says establishing clear eligibility criteria will work because not all patients may be suitable. She says that patient education is vital so that they understand the importance of adherence.
“Knowing how to take and store medication, knowing where and when to collect medication, when to return for appointments, and understanding that they can return to the facility at any time they feel unwell or in the case of an emergency is very important. Adequate supply chain management to ensure an uninterrupted supply of medication along with accurate record-keeping and communication is vital,” she says. “Pharmacists, prescribers, and other staff members involved must also be adequately trained on how to deliver multi-month dispensing.”
Wattrus says in order for the Free State to do well, there needs to be an improved supply chain management system, adequate training for all involved staff, and a well-functioning pick-up point system implemented.
The reality on the ground
However, founder of the lesbian, gay, bisexual, and transgender (LGBT) organisation, Free State Rainbow Seeds, Thabiso Chaka says the Free State can do better in expanding external pickup points. “Once a person has shown interest and is also adhering to their medication, it is a bonus to say now you don’t have to come to the facility every month and every day. You can come after every three to six months. “I believe it is a good strategy to ensure that people adhere to their treatment. The reason why the Free State is doing poorly is because there is also not enough treatment viral load literacy and this creates a serious challenge and the level of care is often compromised because facilities are congested,” says Chaka.
“As the Free State Rainbow seed, we also want to become a CCMD point where we can be able to issue three to six months because by so doing our people will be comfortable.” CCMD (Central Chronic Medicines Dispensing and Distribution) is a government programme that enables stable patients to collect chronic medicines dispensed centrally from designated pick-up points. Chaka says multi-month dispensing of ARVs “is a good approach to limit issues of defaulting because the stigma attached to HIV-positive people is still there”.
According to Judy Mokoena from the Treatment Action Campaign (TAC) in the Free State, there are many reasons why the provincial department is struggling with multi-month dispensing of ARVs.
“The first one is that most facility managers and pharmacists order medication too late. Another reason is that they do not have an actual database of people living with HIV who come to their facilities. What I have noticed is that most people in the province still receive their medication inside the facilities. As TAC, we have been emphasising the issue of giving patients a supply of three to six months, but they are failing dismally,” she says. “Every year we ask the same questions when it comes to the multi-month dispensing, but there has not been a clear answer from government.”
“ARV shortage and ARV theft also play a role and could be another reason why the government is struggling to provide three to six months’ supply,” says Mokoena. “In the past, we have had challenges of stockouts in the Free State.”
