Photo by Miguel Á. Padriñán: https://www.pexels.com/photo/syringe-and-pills-on-blue-background-3936368/
The South African Pharmacy Council (SAPC) has been given judicial go-ahead to introduce its Pharmacy-Initiated Management of Antiretroviral Treatment (PIMART) initiative, which will allow specially trained pharmacists to manage and prescribe medicine to patients with HIV and tuberculosis.
Pretoria High Court Judge Elmarie van der Schyff has dismissed an application brought by a doctors’ organisation – the IPA Foundation – for the setting aside of the programme.
She said the pilot project had emphasised the value of the initiative, which was in line with the World Health Organisation’s vision to promote widely accessible primary health care.
“The untapped value of pharmacists in fighting HIV was also emphasised by the efficient role pharmacies played in meeting health care needs and providing health care services during the Covid-19 pandemic,” she said.
“The need to widen access to first line ART and TPT therapy on a community level is not a figment of SAPC’s imagination but a dire need that is also evinced in other countries.”
The IPA Foundation approached the court, under the Promotion of Administrative Justice Act (PAJA), seeking to review and set aside the SAPC’s decision to implement PIMART.
IPA claimed that the SAPC had failed to give interested parties an adequate opportunity to comment before the initiative was implemented. It further contended that PIMART unjustifiably encroached on the domain of medical practitioners and was in conflict with legislation.
IPA also accused SAPC of misleading the Director-General of Health, claiming there had been extensive consultation with stakeholders, which led to the approval and issuing of permits for the initiative.
The SAPC said the application should be dismissed. It said pharmacy-provided primary healthcare was a well known and functional concept in South Africa and PIMART was simply a “widening of this”.
Referring to the background and context, Judge van der Schyff said, in line with WHO recommendations that all people living with HIV must be provided with ART, the department of health had requested the SAPC to consider and implement interventions that would ensure that patients had increased access to medicines.
This led to the SAPC requesting the Director-General in August 2018 to consider issuing permits to pharmacists who had completed supplementary training, to manage patients and to dispense medication under PIMART.
In March 2021, the SAPC published a notice for public comment regarding the adoption of PIMART. The first permits were issued in August that year.
However, IPA submitted objections outside of the timeline for comments. It said this was because its members were struggling with another wave of the Covid-19 pandemic.
“Pharmacists and doctors operate in distinct and separate professional domains, the boundaries of which are closely guarded and some tension exists … IPA’s objection to PIMART seems to be rooted, partially at least, in this professional tension.
“This is evidenced by its fear that the decision to implement PIMART might ‘open the floodgates’ and ‘pave the way for pharmacists to ultimately treat and prescribe other schedule 4 drugs in respect of acute illnesses’,” the Judge said.
She noted, however, that the National Drugs Policy, in line with WHO guidelines, promoted “task shifting” to advance access to medicine and that at primary level, prescribing should be competency based, not occupation based.
Any alleged adverse effect that PIMART held for a medical practitioner had to be considered against the need to expand primary health care services aimed at preventing and treating HIV and providing first-line ART therapy.
Judge van der Schyff said the initiative gave members of the public a choice as to whether they wanted to approach a pharmacist, who had been issued with a permit, or a general practitioner.
In considering procedural fairness, the judge said there was nothing sinister in the timing of the notice calling for comment, that the project was not something hidden in secrecy and “I find it improbable, as alleged, that none of IPA’s members had timeous knowledge of the board notice”.
The decision to implement PIMART also fell within the ambit of the SAPC’s powers.
Evidence also showed that the PIMART training course was developed to ensure that pharmacists who successfully completed the training would be suitably qualified to safely and effectively assist in providing ART.
Judge van der Schyff dismissed the review application and ordered IPA to pay the costs.
Professor Francois Venter, former President of the Southern African HIV Clinicians Society and Director of Ezintsha, an HIV research organisation at Wits University, commented, “I hope this is the end of it. The pharmacies are an essential part of the health system, and pharmacists internationally play a big role in expanding HIV services.”
In what is likely one of the largest treatment rollouts in South African history, well over four million people living with HIV have started taking the antiretroviral dolutegravir since its introduction around four years ago. Now, according to a recent study published in the Lancet medical journal, use of dolutegravir in South Africa is associated with more people staying on treatment and higher rates of viral suppression.
The use of a three-in-one combination of the antiretroviral drugs tenofovir, lamivudine and dolutegravir (TLD for short) for the treatment of HIV was first recommended by the World Health Organization (WHO) in 2018. A year later it was recommended in the South African treatment guidelines as first line treatment for HIV and a three-year tender was awarded. Since then, dolutegravir has largely replaced another antiretroviral called efavirenz.
Today, TLD is the recommended treatment option for most people living with HIV in the country. The 2023 National antiretroviral (ARV) guidelines also include recommendations for the use of child-friendly formulations of dolutegravir and dolutegravir containing regimens in kids. Spotlight reported on these here.
Around 4.7m people in SA taking dolutegravir
According to Foster Mohale, spokesperson for the National Department of Health, in 2019 the HIV clinical guidelines were revised to include a fixed combination dose of TLD “for all eligible people for use as the first line regimen.”
Based on this, the department set a goal that 90% of those eligible for it should receive TLD as a first line regimen. In terms of meeting this goal, Mohale says that by March 2023, just over four million (4 127 427) people were on TLD. Additionally, about 650 000 (653 884) people were on other dolutegravir based regimens. Altogether, there are thus now over 4.7 million people in the country on treatment combinations that include dolutegravir.
“Based on the March 2023 data, 90% of clients on first line regimen were on TLD. However, performance varies by province,” he says.
Of the total number of people on ART in the public health sector, 75.8% are on TLD, according to Mohale.
Trends in the roll out
While on paper the country’s transition from efavirenz to dolutegravir-based regimens seems to have been smooth, the reality on the ground has been more complex. A study published in the Lancet earlier this year looked at real-world rollout data from 2019 to 2022. The study was conducted in 59 clinics across the country and collected data from two cohorts-one cohort were first time initiators of ART and the other were transitioning from regimens that did not include dolutegravir to ones that did.
In the initiator cohort, just over 45 000 people were initiated on ART between December 2019 and February 2022. Of those, 68.9% were initiated on dolutegravir-based regimens, 31.1% on efavirenz-based regimens, and 0.1% on nevirapine-based regimens.
Those initiated on dolutegravir-based regimens were more likely to still be on treatment a year later and were also more likely to be virally suppressed than those who were initiated on the other regimens.
In December 2019, in the transition cohort, just over 180 000 people were on a non-dolutegravir first line regimen. By February 2022, 67% of them had transitioned to a dolutegravir-based regimen. These people were also more likely to be retained in care at 12 months and be virologically suppressed than those who had not switched to a dolutegravir-based regimen.
“That’s good for a number of reasons. It means that the treatment’s working, people are less likely to get unwell and also, they can’t transmit the virus onto other people,” explains Dr Jienchi Dorward, one of the study authors and an academic clinical lecturer at the University of Oxford and honorary associate scientist at the Centre for the AIDS Programme of Research in South Africa (CAPRISA).
‘Bumpy transition’
Dr Yukteshwar Sookrajh, a Senior Medical Practitioner at the eThekwini Municipality Health Unit who was also involved in the study, tells Spotlight that the rollout quickly gathered momentum.
“But initially there were some issues to navigate around drug interactions; concurrent TB infection and the use of dolutegravir in women of childbearing potential,” he says. “Once those concerns were addressed, the comfort of switching to dolutegravir was increased and we find that the majority of our patients have now safely transitioned across to dolutegravir-based regimens.”
In many ways South Africa was slow in rolling out dolutegravir compared to other African countries, according to Professor Francois Venter, the head of Ezintsha at Wits University. Reasons for this, he says, include an initial concern around the safety of dolutegravir use among pregnant women, and disruption in training due to the COVID-19 pandemic.
He says that the South African Clinicians society was alerted during the COVID-19 pandemic that many patients in the public health sector had still not been transitioned to dolutegravir. An education campaign was then launched to encourage clinicians to start or switch patients to dolutegravir.
However, as it stands now the rollout of the drug in the public sector has been a huge success, despite what Venter calls a “bumpy transition”.
Initial safety concerns
One important reason to conduct the study reported in the Lancet, according to Dorward, was a safety concern regarding the use of dolutegravir by pregnant women. An earlier study conducted in Botswana called Tsepamo found a higher prevalence of neural-tube defects (a type of birth defect) associated with dolutegravir exposure at conception than with other types of antiretroviral exposure. As more data has been gathered since, it has however become clear that dolutegravir does not in fact increase the risk of neural-tube defects.
But the Tsepamo scare did impact who was initiated and transitioned onto dolutegravir in first two years of the rollout.
“The initial concerns around neural-tube defects and the use of dolutegravir in women of childbearing potential clearly hampered rollout of dolutegravir in women – and this has been clearly demonstrated in this study,” says Sookrajh.
The Lancet study found that pregnant women and non-pregnant women were less likely to be initiated on dolutegravir than men early in the rollout, with the biggest difference between women and men aged 15 to 24 years old. This difference decreased with age and by age 55 there was no difference between men and women receiving dolutegravir.
But this changed over time and by September 2021 women were as likely to get initiated on dolutegravir as men. Spotlight previously reported that the rollout was done in two stages. In the first stage men, adolescent boys, women on reliable contraception, and older women were prioritised.
Of those who started treatment during the study period, 46.9% of the pregnant women in the cohort were initiated on dolutegravir-based regimens, while 63.9% of the non-pregnant women and 82.3% of the men in the cohort were initiated on dolutegravir-based regimens.
“In both those groups [cohorts] we found that women were less likely than men to get dolutegravir, but interestingly, this was particularly in younger women,” Dorward explains. “As time went on, the difference between men and women became much less…around June to September 2021 was a time period where we found that women and men pretty much began to equally get dolutegravir.”
Dorward says the data showed an uptick in women in the study being given dolutegravir once the South African guidelines changed to reflect that there was no longer a concern around neural-tube defects. It is thus likely that the safety concern was responsible for the lower initial uptake among young women.
He adds that the messaging around this potential risk was based on the evidence available at the time and was clearly outlined in the guideline document and training for dolutegravir use, but these did not appear to adequately allay these concerns among healthcare workers.
“The risks versus benefits needed to be messaged in a more effective way such that healthcare workers were more comfortable and confident in offering dolutegravir to women,” he says. Based on this experience Sookrajh adds that in future there needs to be more engagement with “practitioners on the ground to determine what type of messaging and supportive materials are required to facilitate better understanding of guidelines at the coal face.”
Another concern for some healthcare workers has been that dolutegravir-based regimens have been associated with greater weight gain than efavirenz-based regimens. But, as argued in a recent editorial in the Southern African Journal of HIV medicine, association is not the same as causation and it may well be that efavirenz inhibits weight gain rather than dolutegravir promoting it. People living with HIV who start taking antiretroviral medicines often gain weight as their health recovers.
New guidelines should further boost uptake
Sookrajh says that the National Department of Health’s antiretroviral (ARV) 2023 guidelines will further improve the uptake of dolutegravir in the public healthcare system.
“With the April 2023 National Department of Health ARV Guidelines, we actually find that further barriers to switching to dolutegravir have been removed and dolutegravir is clearly placed as the preferred drug of choice in almost all scenarios for both first- and second-line antiretrovirals,” he says.
“I think the new [ARV] guidelines hopefully will be a big improvement for people who are on treatment, and part of that is possible because we’re using the drug that is better. You’re less likely to get resistance with dolutegravir so we’re less worried if people don’t take treatment properly that they might get drug resistance, although we still need more research to be sure about that,” Dorward says. “And it’s still very important for people to take treatment consistently to suppress the virus and maintain their own health and prevent onward transmission.”
According to Venter, there needs to be proper resistance surveillance to detect potential dolutegravir resistance.
“We can’t take for granted we’ll never have resistance [to dolutegravir]…eventually there will be the occasional patient that does have resistance, but we need proper surveillance there,” he says. “And then we need to keep an eye on things. There are still patients getting HIV…there’s still a lot of new infections…we need to make that stop…we’ve got amazing PrEP and way too few people getting it. So, we do need to start addressing that.” (PrEP, or pre-exposure prophylaxis, refers to antiretrovirals taken to prevent HIV infection.)
Venter adds that while successful in the public health sector, the uptake of dolutegravir has been extremely slow in the private health sector for reasons unknown to him.
Several sessions at the 11th SA AIDS conference, recently held in Durban, highlighted the worrying fact that key HIV numbers such as treatment coverage are much lower in children than in adults. There is hope, however, that new treatments and new treatment guidelines might help close the gap.
In a plenary session, Dr Sandile Buthelezi, Director General of the National Department of Health, told delegates that on UNAIDS’ 95-95-95 targets, children in South Africa are at 81-65-68. This means that 81% of children living with HIV have been diagnosed, 65% of those diagnosed are on antiretroviral treatment, and 68% of those on treatment are virally suppressed. For the South African population as a whole, the numbers are at 94-76-92.
Throughout the conference, various speakers highlighted the fact that only 65% of children who have been diagnosed are on treatment as a particular concern. To close the gap and reach UNAIDS’ target of 95%, just over an additional 88 000 children would need to be initiated on treatment.
Professor Lee Fairlie, Director of Maternal and Child Health at Wits RHI, said in a presentation that only 52% of children younger than 14 living with HIV are on treatment. Fairlie also pointed out that children lagged behind substantially when it comes to viral suppression, and this is particularly challenging in the youngest age groups.
Not all bad news
But it was not all bad news at this year’s conference. One piece of good news is that new and better child-friendly antiretroviral formulations are being rolled out in South Africa. These new treatments should make it easier for children to start and stay on treatment – children often find it difficult to take medicines formulated for adults, due to factors like incorrect dosing, large pills, and bad taste.
The National Department of Health recently updated the country’s antiretroviral treatment guidelines to allow for the use of several of these new formulations and better HIV treatment regimens for children. Most notable is the introduction of a new regimen consisting of the medicines abacavir, lamivudine and dolutegravir (ALD for short).
Speaking at the conference, Dr Leon Levin, a paediatrician who has been treating infants, children, and adolescents living with HIV for almost three decades, pointed out that the availability of new paediatric formulations had a major impact on the new treatment guidelines. (Spotlight previously reported on the registration of some of these new formulations here.) Levin is also the Senior Technical Advisor in Paediatrics at the NGO Right to Care.
One such child-friendly formulation is a 120/60mg scored, dispersible tablet of abacavir and lamivudine that can be taken in patients who weigh between 3 and 25kg. It is given once daily and two generics are registered with the South African Regulatory Authority (SAHPRA). “It’s going to literally replace all the other paediatric Abacavir+3TC formulations. You can swallow it, chew it, crush it, or dissolve it in water. So [it’s] very versatile,” he said.
Also important is a paediatric formulation of the antiretroviral dolutegravir – a medicine that forms the backbone of HIV treatment in adults. According to Levin, the child-friendly version of dolutegravir is not available to everyone yet, and many clinicians still need to undergo training on how to use it. It is a 10mg dispersible, scored tablet given once daily that can be used at 3kg and higher and from four weeks of age onward. There are two generic versions of this product registered with SAHPRA.
The introduction of paediatric dolutegravir is likely to overshadow the introduction of a four-in-one formulation of abacavir, lamivudine, lopinavir/ritonavir. The four-in-one combination has to be taken twice daily, is strawberry flavoured and comes in a powder form. “Unfortunately, this product to nobody’s fault was launched at the same time as paediatric dolutegravir. Which means paediatric dolutegravir is going to take centre stage and this product unfortunately is not going to be used much,” Levin said.
Updated guidelines
Levin explained that the changes to South Africa’s treatment guidelines focused on doing two main things when it comes to children living with HIV, the first is to implement an optimised regimen – the ALD regimen and the second is to create an “enabling environment to support engagement in care and adherence”. He said that with the new guidelines, we can expect “much improved [viral] suppression, optimised regimens, improved synchronisation of clinic visits, happier patients and their families and clinicians as well”.
A big change to the guidelines is that now children who weigh 3kg and are four weeks of age should be started on the ALD regimen, instead of the abacavir, lamivudine, and lopinavir/ritonavir regimen that was previously recommended. “This is a major change. It’s a fantastic, well-tolerated regimen. It’s potent and you’re going to get around a lot of the issues you had with these younger children,” Levin said.
Once the children on this regimen get to 30kg, they will be switched to a regimen containing tenofovir, dolutegravir, and lamivudine (TLD for short). TLD is also the regimen adults living with HIV in South Africa are offered when starting treatment for the first time.
For children who are already on treatment, the new guidelines recommend that all children who are four weeks of age and older and weigh 3kg or more should be transitioned to a dolutegravir-containing regimen. For children with suppressed viral loads, the switch to ALD or TLD is straightforward, while for children without viral suppression, it can get more complicated.
Another important change is that children over five years of age are now eligible for Repeat Prescription Collection Strategies (RPCs) if they are virally suppressed and had an age-appropriate disclosure, which means that their HIV status has been explained to them in a way that is appropriate for their age, as outlined in the guidelines. For children under five, they can be given a three months supply at a time, providing they are at least six months old. Levin pointed out that whenever RCPs or a three months supply is considered for children, it is essential to look at where and how the parents may be receiving their own antiretroviral treatment so that it can be co-ordinated, and parents don’t have to go to two different places to collect the medications.
New options in the pipeline
While the paediatric formulations included in the new guidelines are a step forward, there are experimental treatments in the pipeline that may make treatment yet more convenient for children.
“There’s a rich pipeline of new combinations and drug delivery developments. Hopefully, this will further improve access, clinical and virological outcomes,” Fairlie said in a conference presentation. “Obviously, the paediatric market is extremely small and then one has to maintain enthusiasm for manufacturers to actually continue to look at the paediatric population. And so, merging of treatments and prophylaxis regimens is really what would work going forwards.”
In her presentation, she specifically referred to long-acting formulations of cabotegravir (CAB-LA) and rilpivirine (RPV). CAB-LA has already been approved by SAHPRA for HIV prevention in adults and, as Spotlight reported last week, pilot projects evaluating how to best provide the CAB-LA injection in South Africa are set to start soon. The combination of CAB-LA and rilpivirine injections has been approved for the treatment of HIV in adults by the United States Food and Drug Administration, but not yet by SAHPRA. The injections are administered every two months.
Fairlie says that currently there are several studies either ongoing or set to start soon for the use of these agents in the paediatric and adolescent age groups. In addition, there are also trials planned to test another long-acting medication called lenacapavir in adolescents and broadly neutralising antibodies (bNAbs) in children.
She also highlighted several improved delivery methods that are in the pipeline for paediatrics. These include a mechanism that doesn’t require water, like oro-dispersible tablets, also known as fast melts, which disintegrate in the mouth as well as oral films that stick to the mouth, disintegrate there, and dissolve. There are also various tablet options that are small enough for children to swallow easily. Like multi-particulates, which are small and solid, multiple-unit dosages that can take the form of granules, pellets, or beads. Mini-tablets are also a prospect – these are compressed tablets no larger than 4ml. Finally, there are novel mechanisms like long-acting oral drug delivery systems and micro-array patches. Fairlie explained that long-acting oral drugs are where a drug is stored in the centre of a capsule that has a number of “arms”, which are able to keep the capsule in the stomach and slowly dissolve and release the drug into the stomach. This allows for slow-release dosing. The “arms” tend to break down after about seven days.
In the RADIANT-TB randomised controlled trial carried out in Khayelitsha, researchers found that tuberculosis (TB) patients with HIV taking a double dose of dolutegravir had similar viral suppression to those taking a single dose plus placebo. The findings, published in The Lancet HIV, suggest that a only once-daily dolutegravir is feasible in patients with HIV-associated tuberculosis.
WHO’s preferred first-line antiretroviral therapy (ART) regimen for adults and adolescents with HIV is dolutegravir, combined with tenofovir and lamivudine or emtricitabine. A disadvantage of dolutegravir is substantial drug–drug interaction with rifampicin, which is important as tuberculosis is the most common cause of hospitalisation and mortality among people living with HIV.
The drug–drug interaction between rifampicin and dolutegravir can be overcome by supplemental dolutegravir dosing, but is a challenge in resource-constrained settings. The researchers sought to investigate whether virological outcomes with standard-dose dolutegravir-based ART are acceptable in people with HIV on rifampicin-based antituberculosis therapy.
RADIANT-TB was a phase 2b, randomised, double-blind, non-comparative, placebo-controlled trial in Khayelitsha, Cape Town, South Africa. Participants were aged over 18 years, with plasma HIV-1 RNA >1000 copies/mL, CD4 count > 100 cells/μL, ART-naive or first-line ART interrupted, and on rifampicin-based antituberculosis therapy for less than three months. Participants were assigned (1:1) to receive either tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus supplemental 50mg dolutegravir 12h later or the same drugs but with placebo in place of the supplemental dolutegravir. Participants received standard antituberculosis therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol for the first two months followed by isoniazid and rifampicin for four months). The primary outcome was the proportion of participants with virological suppression (HIV-1 RNA <50 copies/mL) at week 24 analysed in the modified intention-to-treat population.
No treatment-related dolutegravir resistance emerged in the trial, and though not significant, an increase in insomnia was noted in the supplemental dolutegravir arm. In terms of future research, it is questionable whether a phase 3 trial would be needed given the significant time required for a policy change. Limitations included the study not being powered to compare efficacy.
The authors concluded, “Our findings suggest that twice-daily dolutegravir dosing might be unnecessary in people with HIV-associated tuberculosis. More evidence, from cohort studies or possibly a phase 3 trial, might be necessary to change policy on the need for a supplemental dolutegravir dose with rifampicin-based antituberculosis therapy.”
Both health minister Dr Joe Phaahla and health authorities in the Free State last week denied claims from activists that there are shortages of antiretroviral medicines at health facilities in the province. Authorities did however confirm that some people living with HIV are only given a two-week supply of medicines at a time.
“I can confidently say that there are no stockouts or shortages of ARVs in the Free State,” Phaahla told Spotlight at the World AIDS Day commemoration event in Mangaung.
This was reiterated by spokesperson for the Free State Department of Health, Mondli Mvambi saying, “We do not have shortages of HIV medicines in the province.”
He says allegations of patients not receiving their medication are very serious and cannot be taken lightly. He says should the department hear from patients who are not receiving their HIV medicine, they will investigate.
But Makhosazana Mkhatshwa, a research officer at the Treatment Action Campaign (TAC), says in the past three months, nine clinics in the province indicated that patients have left their facility without the medicine that they needed and of these nine clinics, three of them had sent people home because there was a stockout of HIV medication. She says impacted clinics include Poly Clinic and MUCPP in Mangaung, and Namahadi Clinic in Thabo Mofutsanyana District.
According to community-led monitoring group Ritshidze’s latest report on clinic services in the Free State, there were 40 patient reports this year of shortages of HIV medication compared to 13 patient reports last year. The report states that the most commonly reported medicine shortages by public healthcare users were contraceptives, HIV, and TB medicines. The report was based on monitoring at 28 clinics. TAC is a Ritshidze partner organisation.
Only 7 or 14-day supply for some
One woman Spotlight spoke to at the World AIDS Day commemoration event held in Mangaung last week says she is a patient at Pule Sefatsa Clinic in Botshabelo, Mangaung. “I am forced to go to clinic every week because they only give me a supply for eight days. This is an inconvenience for me because I have to skip work every week just to get my medication.”
Another public healthcare user from Bloemfontein tells Spotlight that for two weeks in October he was stranded without ARVs. He says that he is usually given a 14-day supply at a time. When he requested a full month’s supply to last him through a work-related trip to Cape Town he says his request was declined at the Poly Clinic at Pelenomi Hospital. He says he ended up going without medication.
Aron Malete, District Health Manager for Mangaung, told Spotlight there are no ARV shortages in the district, but asked for details of the above cases so that he could investigate.
The problem is not stockouts per se, but a shortage of medication, says Sello Mokhalipi, Secretary General of Positive Action Campaign. “You will find that there is a shortage of ARVs for seven days, then the next week it will be available,” he says.
Mokhalipi, like other activists Spotlight spoke to, is opposed to giving people only a seven or 14-day supply of medication at a time. He says people should be given enough for three to six months.
When Spotlight put the concerns and calls for multi-month dispensing to Mvambi he says, “We have identified people who are clinic hoppers who steal medicine. They get three months and thereafter run to another clinic to get another three months’ supply. To curb this practice,” Mvambi says, “we keep people on seven and 14 days’ supply The idea is to give them a few days because they claim to have forgotten their clinic cards.”
According to him, people get three months’ supply when they have their clinic card because clinic staff can verify who they are and what medicine they have been receiving.
Doing ‘exceptionally well’ but there are concerns
According to Phaahla who delivered a speech at the World AIDS Day commemoration event, the province has done “exceptionally well in terms of testing, having already surpassed the 94 percent threshold”. Phaahla said 94 percent of people who are living with HIV in the province know their status, 86 percent of those who know their status are on antiretroviral treatment, and 92 percent of those who are on treatment are virally suppressed.
He, however, singled out some districts such as Xhariep and Lejweleputswa where he says the “number of people with HIV and on treatment fare poorly on the target of being virally suppressed”. “This,” Phaahla says, “is very concerning and we must urgently intervene to create a balance among the targets in order to achieve zero new infections by 2030. This includes ensuring that services are brought closer to the people and that our health facilities are adequately resourced with medicine and related necessities.”
“Results for each of the sub-populations vary with adult females at 95 – 91 – 93, adult males at 93 – 77 – 93, and children at 82 – 65 – 68,” says Mvambi. “To achieve the 95 – 95 -95 targets the Free State must increase the number of adult men on ART by 25 745, adult women on ART by 9 744, and children on ART by 5 138.”
“As you can see,” says Mvambi, “the women are more likely to get tested, be initiated on ART, and have their viral load suppressed than their counterparts.”
According to the Free State Department of Health’s latest annual report for the financial year 2021/2022, the number of patients initiated on ARV treatment dropped from 36 776 in 2019/2020 to 26 364 in 2021/2022. In the report, the department states that it failed to meet its target for retaining adults on ART in care. The ART adult remain-in-care rate in 2019/20 was 68%. In 2020/21, it dropped to 52.8% and picked up in 2020/21 at 67.3%. Among the reasons the department cites are the high number of loss to follow-up of clients and “poor tracing by community healthcare workers due to poor supervision”.
NOTE: An employee of the TAC is quoted in this article. 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.
The national Department of Health (DOH) has managed to secure a significant reduction in prices for antiretroviral medicines that treat HIV, with the price of the regimen that is prescribed to most new patients (tenofovir/lamivudine/dolutegravir – TLD) dropping over 30%, from R99 to R68. By comparison the regimen costs well over R250 in the private sector.
TLD is recommended by the World Health Organisation as the preferred first-line regimen for adults living with HIV.
Currently over 4 million South Africans are using this regimen, according to statistics from the DOH. There are about over 5.5 million people receiving treatment for HIV, and 8 million people living with the virus in this country.
Prices of ABC/3TC, commonly used to treat children with HIV, also fell with the DOH’s new contract.
Khadija Jamaloodien, director of the Affordable Medicines Directorate in the DOH, told GroundUp that South Africa is the biggest buyer of ARVs in the world. She said because of the sheer number of people needing ARVs, the department was able to bring the price down.
“Our volumes are just so huge that it makes it more efficient for manufacturers to be able to supply at reasonable prices,” said Jamaloodien.
She said another reason the department was able to reduce the price was that the manufacturers were applying for a three-year contract with “a certainty of demand”. She said constant communication with manufacturers about changes in demand also helped. If demand is likely to be reduced, the department would inform manufacturers who then would not “sit with stock that they are going to have to write off”.
The contract, which is already being executed, was awarded from July 2022 and ends in June 2025.
Jamaloodien said lower prices meant that the department could serve more patients and provide more medicines within the same budget envelope. (ARVs are provided free to public sector patients.)
Juliet Houghton, CEO of the Southern African HIV Clinicians Society (SAHCS), praised the DOH’s efforts to secure the ARVs so cheaply. She said a “healthy” degree of competition between manufacturers also helped drive prices down.
Houghton added that the reduction in prices “offers an opportunity to reinvest some of the savings into more expensive, particularly prevention drugs, that are coming”.
“As a country, we don’t want to just keep treating more and more people with HIV, we actually want to prevent it,” said Houghton. She said that the remaining budget could also be invested in prevention injectables, which might be more expensive.
Jamaloodien said that the injectable pre-exposure prophylaxis (PrEP) medicines are not yet registered with South African Health Products Regulatory Authority (SAHPRA). These help prevent sexually active people from contracting HIV. She said after the medicines are registered, they will have to look at whether they are affordable.
Francois Venter, executive director of Ezintsha at Wits, also praised the DOH’s “excellent work in securing these price reductions”.
“We also need the department to start using these processes better to secure similar world-class treatments for other common diseases – including diabetes, cancer, obesity, and TB,” he said.
The Treatment Action Campaign (TAC) has called on former president Thabo Mbeki to offer an apology to the public for the “dissident” views he expressed about HIV/AIDS while delivering a speech at the University of South Africa (UNISA) last week Wednesday.
In a scathing statement published by the TAC on Tuesday, the organisation said the “repetition of his scientifically erroneous views with such insensitive arrogance is an insult to the 8 million people living with HIV in SA and the families of 4 million South Africans who have died from HIV over the last three decades”.
Mbeki, who is also the Chancellor at UNISA, was speaking to students, diplomats and members of the media at an event which takes place twice each year and allows students to interact with him on pertinent issues that affect Africans.
The TAC accuses Mbeki of misleading the public when he questions the cause of AIDS. The organisation also goes on to say that they were stunned again by Mbeki’s support of the views of the late former Minister of Health, Manto Tshabalala-Msimang “who was ridiculed for promoting garlic and beetroot as the essential ingredient to manage AIDS, giving it a higher premium than antiretroviral (ARV) treatment”.
“Whilst there may be benefits in all healthy foods, the idea that these vegetables are what are most required in the management of AIDS has no basis in fact and is misleading to the public,” said the statement.
Speaking about HIV/AIDS after a question was raised in the event, Mbeki said the questions that he raised then, he would still raise today. He emphasized that AIDS was a syndrome and not a disease.
“Now this syndrome in medical terms is a group of diseases. So all of these diseases which fall under this syndrome, meningitis, TB, they’re in the syndrome.”
“Causes of Tuberculosis are known and historical, but it’s part of the syndrome. So you can’t say one virus causes all of these illnesses, what you can say is this virus impacts negatively on the immune system, it’s that weakened immune system which results in a syndrome.”
“But there’s a consequence to that kind of thinking which is when you go to test and that test says HIV positive… it does not necessarily mean you’ve got the virus. What it means is that the immune system is responding to something that is threatening the body, and therefore you need a clinical analysis in order to determine what is this thing that the immune system is rejecting. It’s in all the medical documents that go about it, and it’s correct, because then you have to go and do this clinical examination in order to determine which of these illnesses in the syndrome is the one that’s affecting this person. And then you treat the person for that particular disease,” said Mbeki.
Mentioning the views of Tshabalala-Msimang, Mbeki started off by saying as government they had to respond in an effective manner to the HIV/AIDS pandemic and various interventions were needed to do this.
“Which is why the question was raised by the then Minister of Health in a very dramatic fashion. Nutrition. Nutrition is very very critical to solving this problem and that’s why she was saying that we must take garlic and beetroot and so on. She was not saying that with those things you’re going to be cured.”
“She was raising the matter about the importance of nutrition. And those particular types of foods even today have been raised in the context of this Covid-19,” said Mbeki.
The TAC, which successfully campaigned in the 2000s for Mbeki’s government to roll out life-saving medicines, was not impressed.
“There is much ongoing stigma and denial when it comes to HIV and we call on Mr Mbeki to desist from statements about HIV that have no basis in fact,” said the TAC statement.
It said: “The former president’s statements remind us that his unscientific views led to a delay in the rollout of the ARV programme during his presidency.”
The TAC’s General Secretary, Anele Yawa, said that if Mbeki was not prepared to apologise, the organisation would make sure that his HIV denialism and the thousands of deaths that resulted, would be the only thing that he would be remembered for.
These are the facts when it comes to HIV/AIDS under Thabo Mbeki’s presidency
By Nathan Geffen, GroundUp Editor
It’s seldom clear what Thabo Mbeki means when it comes to HIV/AIDS. There is much obfuscation. But the key facts are this:
HIV destroys immune system cells in infected people.
Usually over a period of several years, if left untreated, the immune system collapses, causing the person to become ill with life-threatening infections. This is known as AIDS.
Only antiretroviral medicines can halt this process. They have been so effective that the life-expectancy for people with HIV who take them is brought back to almost normal.
HIV tests are reliable. If proper protocols are followed the odds of an incorrect result are extremely small.
Mbeki’s government delayed the rollout of antiretroviral treatment in the public sector until 2004, even though an effective combination of antiretroviral medicines was available from the mid to late 1990s.
It was only due to pressure from the TAC and its allies that Mbeki’s government made antiretrovirals available in the public sector.
The prices of these medicines also became affordable because of the TAC’s (and its allies) campaigning against pharmaceutical companies. Mbeki’s government was largely AWOL in these efforts, despite Mbeki’s rhetoric about these companies.
Two different studies have estimated that the delayed rollout of antiretrovirals resulted in well over 300 000 avoidable deaths. These estimates are conservative.
These estimates also exclude those who died because they were convinced by Mbeki, Tshabalala-Msimang and their acolytes to try treatments promoted by as alternatives to antiretroviral medicines. The promotion of these nonsense remedies by Mbeki and his health minister continued long after the antiretroviral treatment rollout began.
Geffen was involved with the TAC from 2000 to 2013.
Dolutegravir-based antiretroviral therapies (ART) for HIV-1 are more effective for pregnant individuals than some other ART regimens commonly used in the US and Europe, according to a study available online in NEJM.
The study, led by Harvard T.H. Chan School of Public Health researchers, showed that pregnant individuals who took dolutegravir-based regimens had a high probability of being virally suppressed at delivery. No differences were seen in adverse birth outcome risks (preterm birth, low birth weight, small for gestational age, or neonatal death) between dolutegravir-based regimens and the other contemporary regimens.
“Globally, a dolutegravir-based regimen is currently recommended for treating HIV, and this is the first study to directly compare regimens including dolutegravir to other antiretroviral regimens, such as raltegravir-based regimens, that are also listed as ‘Preferred’ in US perinatal guidelines,” said senior research scientistKunjal Patel, lead author of the study.
Dolutegravir, is a newer antiretroviral part of a once-a-day regimen that has been shown to be more effective, easier to tolerate, and less likely to create new drug resistance in people with HIV-1. However, limited data have been available about its effectiveness and safety in pregnancy compared with regimens that commonly have been used during pregnancy in the US and Europe.
In the current observational study, the researchers compared dolutegravir use in pregnancy with atazanavir/ritonavir, darunavir/ritonavir, and raltegravir antiviral regimens that are currently classified as “Preferred” for use in pregnancy in the US About half of the participants started ART before conception. At delivery, 96.7% of pregnancies of participants who received dolutegravir were virally suppressed, whereas those of participants who took atazanavir/ritonavir or raltegravir had viral suppression of 84.0% and 89.2%, respectively.
“We think the observed differences are due to dolutegravir’s ability to rapidly decrease viral loads and its ease of use as part of a once-daily regimen that’s available as a fixed-dose combination,” said Patel. “Our results highlight the continual need for systematic studies that compare new antiretroviral regimens with those already in clinical practice to help inform the evolution of guidelines and clinical practice over time.”
Specifically designed cocktails of broadly neutralising antibodies (bNAbs) could help treat HIV while minimising the risk of the virus escaping treatment, researchers reported in eLife.
The study shows that computational approaches to selecting combinations of bNAbs based on viral genetics could help prevent viral escape, making HIV treatment more effective. It may also offer a strategy for designing effective combinations of bNAbs for treating other rapidly evolving pathogens.
bNAbs offer a promising new tool to treat or potentially cure infections with rapidly evolving viruses such as HIV. Clinical trials using a single bNAb to treat HIV have shown that some viral strains may survive the treatment and lead to a rebound of viruses in the blood. Combinations of bNAbs may therefore be a more effective approach, but finding the best combinations is a challenge.
“For our study, we proposed using a computational approach to predict the effectiveness of bNAb combinations based on the HIV genetics,” said researcher Colin LaMont.
LaMont and colleagues analysed the genetics of HIV viruses collected over 10 years from 11 untreated patients with HIV, and used this data to predict which viral strains might be able to escape treatment with different bNAbs and whether dodging bNAbs had a survival cost. Next, using computational methods, they applied the knowledge gained to predict viral rebounds in three real-life trials of bNAbs.
Finally, the team used their computational approach to find a combination of bNAbs that is least likely to allow any virus to escape. They also found that some bNAbs, such as 10-1074, are better against diverse populations of viruses because mutations that allow viruses to escape also make the virus less likely to survive. Others, including PGT121, are more effective against less diverse viral populations because mutations that enable escape are rare. Overall, the results suggested that the optimal combination includes three bNAbs: PG9, PGT151 and VRC01.
“We’ve shown the combination of PG9, PGT151 and VRC01 reduces the chance of viral rebound to less than 1%,” LaMont said. “It does this by targeting three different regions of the virus’ protective outer wrapping, or envelope.”
“Combining bNAbs, administered via intravenous infusion every few months, with current antiretroviral therapies (ART) that require daily doses could further improve long-term HIV treatment success,” suggested senior author Armita Nourmohammad, Assistant Professor at the University of Washington.
ART hinders HIV multiplication and ability to create new variants, limiting the genetic diversity of the viral population and reducing the odds of bNAb escape variants emerging. The authors say that more studies are needed to confirm the potential benefits of combining ART and bNAbs.
“Our study shows that leveraging genetic data can help us design more effective HIV therapies,” Asst Prof Nourmohammad concluded. “Our approach may also be useful for designing therapies against other rapidly evolving agents that cause disease, such as the Hepatitis C virus, drug-resistant bacteria, or cancer tumour cells.”
The South African HIV Clinicians Society (SAHCS) have recently announced a clinical update on the dolutegravir (DGT)-based regimens for first- and second-line antiretroviral therapy. This comes in the wake of positive findings from a number of clinical trials.
“Based on data from several recent trials, we now recommend that all patients > 10 years old and 35 kg on tenofovir/emtricitabine (or lamivudine)/efavirenz (TEE/TLE) or NVP-based regimens be switched to tenofovir/lamivudine/dolutegravir (TLD) regardless of the viral load (VL) result. In addition, all patients > 10 years old and > 35 kg on a regimen of two nucleoside reverse transcriptase inhibitors (NRTI) with a boosted protease inhibitor (PI) (eg, lopinavir/ritonavir (LPV/r) or atazanavir/ritonavir (ATV/r)) and a suppressed VL can be switched to TLD, regardless of prior resistance patterns or treatment history.”
In South Africa, pre-treatment resistance to nonnucleoside reverse transcriptase inhibitors (NNRTI)-based antiretroviral therapy regimens has been rising. Meanwhile, DTG has a higher barrier to resistance and reduced side effects. This prompted the Department of Health to recommend that patients on NNRTI-based ART regimens be switched to DTG-based regimens. This transition is slower than desired partly because a documented suppressed VL is required prior to switching from TEE/TLE to TLD. Since this recommendation was first made, evidence from several trials (NADIA, VISEND and ARTIST) has demonstrated that tenofovir with lamivudine can be safely and effectively recycled from a first- to a second-line regimen. Therefore, the SAHCS has stated that “in patients with virological failure on a TEE or TLE regimen a single drug can be switched (efavirenz to dolutegravir ie, TLD as secondline), resulting in virological suppression comparable to or better than alternative second-line options.”
The guidelines also outline the results of the NADIA, VISEND and ARTIST trials conducted in southern African countries, as well as the single-arm DAWNING trial.
