New tuberculosis medicine studied in South Africa approved in United States

By Amy Green

Despite the fact that often-deadly extensively drug-resistant tuberculosis (XDR-TB) is found in roughly 127 countries, up until now it has been treated with a ‘kitchen sink’ approach. Doctors, using their discretion, throw many often-toxic drugs into a lengthy treatment regimen – unsure if the combination will lead to a cure. XDR-TB is by definition resistant to many key tuberculosis medicines used today.

The United States Food and Drug Administration (FDA) on Wednesday approved the medicine pretomanid used in combination with specific other medicines for the treatment of XDR-TB. The approval brings hope to many in the field while others see the move as hasty and caution that it may set a dangerous precedent. Pretomanid is only the third new TB medicine to be approved by a leading regulatory authority in the last fifty years following on bedaquiline and delamanid earlier this decade.

Pretomanid was approved for use as part of a combination regimen including existing drugs bedaquiline and linezolid for the treatment of adults with pulmonary XDR-TB and treatment-intolerant or non-responsive multi-drug resistant TB (MDR-TB).

This three-medicine regimen, called BPaL, drastically shortens the treatment duration for XDR-TB from the current 18 months or longer to just six months. It has been shown to cure around nine out of 10 XDR-TB patients in a trial conducted in South Africa.

One of the principle investigators for the NixTB trial – which generated most of the evidence for the FDA decision – local scientist Dr Francesca Conradie described this as a “watershed” moment for the fight against hard-to-treat forms of TB.

“The annals of time are measured before and after Christ, whether you agree with that or not. Now people will refer to the history of drug-resistant TB as pre-Nix or post-Nix – that is the significance,” she said.

Paul Sommerfeld, who heads up the United Kingdom-based non-profit TB Alert, said drug resistant -TB has been a death sentence for far too many people for far too long.

“With pretomanid and other new drugs, cure rates for XDR-TB can be greatly increased,” he said. If there is also political will to introduce these drugs in every country, local communities and the individuals within them facing treatment can truly believe that they will be cured and in much shorter time with safer, more tolerable medication than those used in current regimens.”

But some have raised concerns that the decision is based on weak evidence and could set a dangerous precedent for other novel TB drugs in the future.

“We are excited and encouraged about the opportunity for people with difficult-to-treat forms of TB to have access to shorter and simpler treatments,” Lindsay McKenna, from the United States’ Treatment Action Group (TAG), told Spotlight.

“But we are concerned that this regimen, and specifically the new agent pretomanid, was only studied in a small group of 109 patients in the NixTB trial, which goes against the usually-stringent requirements of most new medicines,” she said.

Also, she said, the NixTB trial was started in a time where the prognosis for patients with XDR-TB was extremely poor, and much has changed since drugs like bedaquiline and delamanid have come into wider use over the past few years.

For example in South Africa, in 2012, only 19% of XDR-TB patients used to be cured even if they completed the gruelling two years of toxic treatment, according to the National Department of Health’s head of drug-resistant TB Dr Norbert Ndjeka. By 2016, 67% of XDR-TB patients in South Africa given bedaquiline were cured.

While BPaL achieved 90% cure rates in a clinical trial setting this might not be the same in a programmatic setting which has less patient support and more confounding factors.

However, said Ndjeka, more than one in 10 people drop out of current XDR-TB treatment because of its long duration and multitude of side-effects, risking death as well as the spread of this resistant bacteria in their communities. According to Ndjeka, having a drastically shorter regimen with much fewer side-effects could improve the drop-out rates.

A single-arm trial

McKenna noted that the single-arm NixTB trial was not randomised and controlled, which is the usual standard by which new drugs are measured by regulatory bodies.

Conradie said that NixTB couldn’t ethically include a control arm, which would compare BPaL with the then standard of care, because historic XDR-TB treatment has such devastatingly poor success rates.

“It is a small body of evidence, I agree. While 109 patients were exposed to pretomanid in NixTB, over 1,000 in total have been exposed to the drug. We know it is safe. It doesn’t cause heart or liver problems. And there are many incidences of drugs being registered without a control arm where there were clear benefits to the regimen and where clinicians had no other treatment options for example with hepatitis C,” said Conradie.

McKenna said that while this is true, TAG would advocate for more studies to be undertaken to compare BPaL with, for example, the current bedaquiline-containing 18-month regimen currently being used in South Africa.

There are also questions about the benefit of pretomanid over delamanid, another new TB drug which has already been studied in higher numbers of patients and is already registered in many countries. The drugs have a similar mode of action and activists have called for a head-to-head study comparing BPaL to a similar regimen that replaces pretomanid with delamanid.

In its submission to the FDA about the BPaL regimen, TAG requested the body to grant pretomanid conditional approval, as it has done in the past for urgently-needed drugs with smaller bodies of evidence. Such conditional approval would have required pretomanid innovator the TB Alliance to conduct further trials of pretomanid to keep its approval status.

According to the Global TB Community Advisory Board’s testimony submitted to the FDA, full approval for pretomanid could “set a precedent with the potential to lower the evidentiary standard for the future approval of new TB drugs and regimens” noting the importance that “well-intentioned efforts to expeditiously serve the needs of TB patients today do not inadvertently do a disservice to TB patients in the future”.

Implications for South Africa

But what does a decision made by a United States’ regulatory body mean for South Africa?

The World Health Organisation (WHO) is set to discuss this evidence in a November meeting, meaning the earliest time it would issue recommendations to this effect would be early next year. Previously South Africa had not waited for WHO approval to make changes to its TB programme, as was the case with the introduction of the TB medicine bedaquiline.

“Most of the research has been done in South Africa and clearly we would like to be either the first country, or among the first, to offer it to patients,” said Department of Health deputy director-general Dr Yogan Pillay. “But the issue is cost. Because the numbers of patients with XDR-TB are small, around 1,000 a year, it would be hard to negotiate price reductions based on large numbers.”

Rather than a routine and programmatic adoption of the regimen into the country’s guidelines, the department is looking to reach an arrangement where the BPaL regimen would be used in an “operational research setting”.

Pillay said that in anticipation of the FDA’s announcement, a meeting had been arranged for August 20 with stakeholders to discuss this potential arrangement with the focus being on multi-drug resistant TB (MDR-TB) patients. MDR-TB is TB that is resistant to rifampicin and isoniazid, two of the key tuberculosis medicines.

Although the focus on MDR-TB might seem peculiar, Ndjeka said that “there are 10 times as many MDR-TB patients, 10,000, compared to 1,000 XDR-TB patients a year, and for us the real benefit will come when we give newer and more effective regimens to greater numbers of people”.

The latest available data on the bedaquiline-containing nine-month MDR-TB regimen in the country showed a 73% cure rate and a 9% drop-out rate.

The objective would be to garner evidence for the BPaL regimen’s efficacy in MDR-TB to inform local and global guidelines to this effect. While Ndjeka said his department will also advocate for the inclusion of XDR-TB patients in this operational research arrangement – which could mean the country accesses the drugs for free – “it will still be a good thing if we only get it for MDR-TB”.

Even though the country won’t need to wait for WHO approval, Ndjeka said that “unfortunately it’s not a TB programme decision and involves the South African Health Products Regulatory Authority and other stakeholders”.

He added that it took about 18 months for both bedaquiline and delamanid to get past the red tape required to introduce the drugs locally.

“Realistically, considering the bureaucracy we’ve experienced in the past, I see it only coming to South Africa next year June or maybe even August – and that’s if we are fast,” he said.

Marius, a Cape Town-based participant in the Nix-TB trial, said that prior to joining the trial, lengthy treatment for XDR-TB in 2011 interfered with his job and quality of life. “I couldn’t take it anymore. For nine months I took 23 tablets every day. Every day, an injection. It was terrible and still I was not being cured. I felt dizzy the whole day and could only stay lying down,” he said.

A six-month course could help patients keep their jobs as they would need less time off work and could contribute to the wellbeing of entire families when bread winners fall ill.

Said Marius: “This new treatment is good. I can do what I want to do. And I feel like the old Marius again.”

Disclosure: Spotlight editor Marcus Low is a member of the Global Tuberculosis Community Advisory Board referred to in this article.

The plan to revive medicines regulation in South Africa

By Catherine Tomlinson

The South African Health Products Regulatory Authority (SAHPRA) is responsible for the regulation of medicines in South Africa to ensure that medicines marketed in the country are safe, effective and of good quality. In addition, SAHPRA is responsible for the regulation of medical devices, clinical trials and radiation-emitting devices.

SAHPRA replaced South Africa’s previous medicine regulatory authority, the Medicines Control Council (MCC), in February 2018 with the objective of creating an effective regulator that is responsive and publicly accountable and able to make timeous regulatory decisions. However, SAHPRA inherited many historical challenges that plagued the MCC, including slow regulatory decision times, an extensive backlog of pending regulatory applications, and a culture of non-transparency and resistance to public accountability. Since its formation, SAHPRA has developed a range of plans to overcome these challenges, which were outlined in its recent 2019/2020 annual performance plan.

Inherited challenges

At its establishment, SAHPRA inherited a massive backlog of around 16 000 medicine regulatory applications from the MCC. These include applications for “new registrations, variations, duplicates, clones, multiple doses and different dosage forms”.

While 50% of backlogged applications were submitted in the past five years, the backlogged applications date all the way back to 1992 and include applications for high priority public health products, including medicines for HIV, tuberculosis, cancer and diabetes.

The University of Western Cape’s Henry Leng and colleagues have highlighted the adoption of policies to promote generic access as key drivers of the accumulated backlog. In the early 2000s, South Africa adopted policies to fast-track the registration of medicines of high public health priority and to promote generic access. The adoption of these policies led to a large influx of applications for the registration of multiple generic versions of high priority products.

In general, the registration and availability of multiple generic versions of individual medicines is critical to improving medicine access, because competition between generic suppliers drives down prices and improves affordability. Research conducted by the United States’ medicines regulatory authority, the Food and Drug Administration, has shown that it generally takes the introduction of multiple generic products to bring down prices, as the first generic companies to enter the market tend to price their products close to the prices offered by originator companies.

While broad generic competition plays an important role in enabling medicine access, the introduction of policies to promote generic access in South Africa contributed to a regulatory backlog, as they were not coupled with an expansion of capacity at the regulator to process the influx of applications. At the same time, South Africa has struggled with “frivolous” regulatory filings by companies that fail to market their products after receiving registration. In a review of eight priority medicines, Leng et al. found that only 54% of registered generic medicines were actually marketed in the country following registration. Leng et al. suggested that the comparatively low cost of filing for registration in South Africa may encourage filings by companies without serious intentions to market their products, and cautioned that time and resources spent by the regulatory authority on fast-track approval of unmarketed products for which there are already existing alternatives, delays the registration of new products for which there is no equivalent in the country, or existing competition.

Inadequate capacity

SAHPRA has indicated that even without the large inherited backlog, the regulatory authority does not currently have the capacity to timeously process new applications. Evidence shows that while SAHPRA receives an average of 4 700 new applications annually, it is only able to process around 2 550 applications per year. With inadequate capacity to process backlogged and new applications, timelines for registration of medicines in South Africa are typically extremely long.

Research conducted by Keyter et al. demonstrated that the median time for approval of new chemical entities by the MCC was 1 161, 1 678, and 1 422 calendar days in 2015, 2016 and 2017, respectively. Keyter et al. further demonstrated that the median time for approval of fast track applications was 1 218, 921, and 609 calendar days in 2015, 2016 and 2017, respectively – far slower than the regulatory authority’s target for approval of fast-track applications in 250 days.

Slow regulatory decision times in South Africa have serious public health consequences, as they impede access to important and life-saving medicines, as well as cheaper generic versions of medicines, long after they are available on the global market. Recognising this challenge, SAHPRA has set a target to reduce regulatory decision times to 275 working days for new chemical entities and 180 days for registration of generic products. SAHPRA has also set a target to clear the regulatory backlog in two years.

The recently released annual performance plan outlines SAHPRA’s plans to “re-engineer” the regulatory authority to achieve its targets. Its plans include (among other interventions) the strengthening of its human resource capacity, the introduction of a new fees model and the digitisation of key processes.

SAHPRA’s strategy to address the medicine regulatory backlog

SAHPRA has set a target to clear the regulatory backlog in two years – but notes that, at current capacity with no new applications, clearing the backlog will take up to eight years. SAHPRA’s annual performance plan clarifies that the regulator has developed a costed strategy to clear the backlog and has secured ring-fenced funding for the backlog clearance strategy from the government, development partners and donors.

SAHPRA’s strategy to reduce the backlog involves three key elements, including reducing the number of backlogged applications to remove applications that are no longer relevant, prioritising the remaining applications for review according to public health needs and risk, and implementing new regulatory pathways to reduce regulatory decision times.

Given that the regulatory backlog dates back to 1992, it is expected that some applications may no longer be of commercial interest to applicants or of public health relevance. SAHPRA will seek to remove applications that are no longer relevant through requiring applicants who submitted applications in 2013 or earlier to indicate that they would still like their applications to undergo review through a survey template and requiring all applicants to update their applications to meet current requirements. SAHPRA has already begun to implement this and noted in a May 2019 communication that 3 000 applications in the backlog have already been deemed to be withdrawn. Moving forward, SAHPRA has indicated that it will prioritise the remaining backlogged applications for review according to public health risk and need. Public health need will be based on the government’s priority therapeutic areas and unmet medical need, and public health risk will be based on the complexity and type of application and “level of prior scrutiny by recognised regulators”.

In addition to reducing the number of applications and prioritising applications for review according to public health need and risk, SAHPRA has committed to implementing “new evaluation models” to clear the backlog, as well as to facilitate timeous registration of new applications. This strategy will involve the implementation of so-called reliance pathways to facilitate greater collaboration and information sharing with other regulatory authorities.

Reliance pathways provide mechanisms for collaboration across global regulatory agencies, and with the World Health Organisation, by creating pathways that allow regulators to access and use data and reports, and rely on other evaluator decisions, in domestic regulatory decision making. Reliance pathways provide important mechanisms to reduce times to regulatory decision making when capacity challenges impede timeous local decision making. Medicine regulators in both developing and developed countries struggle to manage their workloads and make timeous regulatory decisions due to increasing application volumes, and the need to monitor the compliance of foreign producers to good manufacturing practices (GMP).

Historically, South Africa’s medicine regulators (the MCC and SAHPRA) have not utilised reliance pathways – despite arrangements and collaborations in place with other regulatory bodies to facilitate their use – and selected instead to conduct full scientific reviews of quality, efficacy and safety data for all regulatory applications. However, SAHPRA has now committed to operationalising these pathways to address the backlog and reduce regulatory decision times for new applications. SAHPRA has further indicated that it will formalise processes to facilitate the use of several different reliance pathway models, including full review, abridged review, verified review, recognition and notification – each requiring different levels of local review and evaluation.

Implementation of the “abridged review” model, for example, would allow SAHPRA to rely on regulatory data and evaluations from other agencies (such as the European Medicines Agency), while requiring local review and evaluation of domestic contextual issues – such as the interaction of the medicine under review with HIV treatment.

Building SAHPRA’s human capacity

A further challenge faced at SAHPRA is its limited human resource capacity to effectively fulfil its mandate. According to information provided to Spotlight by SAHPRA’s CEO Portia Nkambule in November 2018, SAHPRA then had 178 full-time employees and around a similar number of external evaluators supporting regulatory activities. SAHPRA is seeking to significantly increase its staff capacity to around 450 full-time staff over the next five years and has already initiated a hiring drive, advertising more than 100 new posts in May 2019. SAHPRA has further indicated that staff members were recently transferred from the National Department of Health’s Pharmaceutical Trade and Product Regulation programme to SAHPRA under a section 197 transfer agreement and, according to SAHPRA’s annual performance plan, the transferred staff will support core programmes responsible for medicines evaluation and registration and authorisation management.

While SAHPRA is seeking to strengthen staff capacity in all of its programmes, the 100 recently advertised posts included 17 new posts for medicines regulation and 19 posts for the backlog clearance project. A key goal of SAHPRA is to build its internal capacity to fulfil its medicines regulatory functions, unlike the MCC which relied heavily on external evaluators. SAHPRA’s annual performance plan explains that its reliance on a “dwindling” number of external evaluators creates difficulties in managing and optimising regulatory decision times due to the lack of contractual performance agreements with external evaluators. The annual performance plan clarifies that while SAHPRA hopes to absorb some external evaluators as internal staff, it will also seek to build its internal capacity through upskilling existing staff and recruiting new staff – but notes challenges in attracting and recruiting new internal evaluators.

SAHPRA did not respond to requests for more information on the difficulties it is facing in recruiting new internal evaluators. However, recruiting challenges faced by SAHPRA may include challenges identified by regulatory authorities in other jurisdictions – such as shortages of required skills in the domestic labour market and difficulties in competing with higher salaries offered by the industry.

Opportunities and challenges for public engagement

SAHPRA has taken significant and commendable steps since its establishment in February 2018 in outlining reform plans and processes to improve its functioning to effectively fulfil its mandate. In addition to the adoption and initiation of a strategy to address the regulatory backlog and its efforts to build its staffing capacity, SAHPRA has developed plans to digitise key processes and implement a new fees model (among other interventions). These steps have been taken despite significant challenges faced by the new regulatory agency in its first year of operations, including staff protests and the closure of its offices in the Civitas building due to unsafe working conditions.

While SAHPRA should be commended for its important work to date, responsiveness to the public and accountability remains a challenge despite the regulators commitments to improving and demonstrating transparency and accountability. Health NGOs in South Africa continue to express frustration due to the non-responsiveness of the regulator following requests for information and engagement. Additionally, despite questions Spotlight sent SAHPRA for this article, no responses were received.

In December 2018, SAHPRA CEO Nkambule noted that the regulatory authority was seeking to create a culture of transparency and that in the current transitional phase it would prioritise the implementation of a formal communications strategy and systems. SAHPRA’s annual performance plan notes that a communications strategy has been drafted and has been approved to be implemented during 2019. The plan further adds that through implementing the communications strategy, SAHPRA will endeavour to (among other goals) “develop mechanisms to allow all stakeholders to communicate easily with the regulator including being able to lodge queries and complaints”.

Beyond the implementation of a communications strategy, the Minister of Health should introduce legislative reforms to require greater transparency and accountability from SAHPRA. Vawda and Gray recently undertook a review of secrecy provisions contained in section 34 of the Medicines and Related Substances Act No 101 of 1965 and concluded that section 34 “violates the right to access to information in section 32 of the Constitution of SA”. They added that section 34 “appears to grant the MCC/SAHPRA unfettered authority to refuse access to information, except on limited grounds, based on its sole discretion”. Vawda and Gray recommended the amendment of section 34 to accommodate the right to access to information and added that the regulatory reform processes underway “provides an opportunity to redress a serious anomaly in our regulatory framework, and to align it with our constitutional paradigm, in order to reflect greater openness, transparency and accountability in our public institutions”.

As SAHPRA moves forward with the development and implementation of plans to re-engineer the authority, there is significant scope for civil society to monitor developments to demand meaningful transparency and accountability from the regulator (including necessary regulatory reforms) and ensure that the development and implementation of reforms serve the public interest.

 

 

 

HIV in SA: Seven graphs that tell the story

By Marcus Low and Sean MacDonell

The recently published outputs of the Thembisa mathematical model (version 4.2) of HIV in South Africa paint a remarkable picture of the history of HIV in this country. For the period from 1990 to 2019, we’ve plotted seven graphs below using the estimates published on the Thembisa website. For all the graphs, a solid line indicates data which have been ‘matched’ against available survey data, while a dashed line represents data that are more uncertain as they are the Thembisa model’s projections or ‘best guesses’ based on previous trends in the data. A shaded region surrounding a line represents the upper and lower estimate (or 95% confidence interval).

Life expectancy

This graph shows life expectancy at birth in South Africa. It shows a dramatic drop to 53.2 as the HIV epidemic grew to its peak in 2004. The impressive increases since then has been attributed to the wide rollout of ARVs by the state (see next graph). This graph also makes it clear that, impressive as these increases are, they are only a relatively modest improvement on pre-HIV levels. Life expectancy in 1994 was 62; 25 years later in 2019 it is estimated to be 66.5.

Antiretroviral treatment (ART)

This graph shows the total number of people in South Africa receiving antiretroviral treatment. Comparing this to the previous graph, notice how dramatically life expectancy increased as antiretrovirals (ARVs) became more widely used from the mid-2000s.

Number of new infections and HIV deaths

The blue line on this graph shows the number of new HIV infections in South Africa by year. The good news is that the rate of new infections is decreasing from its peak of around 570 000 per year at the turn of the century. The red line represents HIV deaths per year and shows that yearly deaths peaked in 2005 at around 284 500 and then started declining (note the similar time that ARVs became more widely used in the previous graph). Notice how the red line is lower than the blue line – in other words, more people are becoming newly infected with HIV than people are dying of HIV. The result of this, as we will see in the next graph, is that the number of people living with HIV in South Africa is increasing. (Not shown on the graph: by 2019 a total of around 3.6 million people have died of HIV-related causes in South Africa.)

Number of people living with HIV

This graph shows the number of people living with HIV in South Africa. That this number is continuing to increase is both a bad and a good thing. As we can see from the previous graph, this effect is driven by the still high rate of new HIV infections (bad) and by the fact that people living with HIV are living longer and no longer dying at the same rates as before (good).

HIV prevalence

This graph shows HIV prevalence in South Africa. It is worth including here since HIV prevalence figures are often quoted in the media. Prevalence in this case is an indication of the percentage of the population who are living with HIV in a particular year. Prevalence is driven by the same forces driving the total number of people living with HIV (shown in the previous graph). The one key difference is that it also factors in that the total population of South Africa is growing. If you extend the model’s predictions into the future, HIV prevalence is expected to stay at around 12.9% until 2024, when it is anticipated to start coming down slowly – while the total number of people living with HIV is anticipated to keep increasing to around 8.2 million by 2030.

Viral suppression

This graph shows the percentage of people living with HIV in South Africa in whose bodies HIV has been suppressed to the extent that they are essentially non-infectious. It suggests that from 2018 more than half of all people in South Africa who are living with HIV are non-infectious. It also indicates that by 2018 the virus was not suppressed in around 46% (over 3.4 million) people living with HIV in South Africa – getting more of these people onto treatment and virally suppressed will be critical to reducing the rate of new infections.

A telling ratio

One way to assess South Africa’s HIV response is to compare the rate at which people are started on antiretroviral therapy with the rate at which people are becoming newly infected. If more people are being started on treatment than becoming newly infected, things are going in the right direction. This graph shows the ratio between these two numbers. It indicates that the rate at which people were starting ART only became greater than the rate of new infections in 2009. As long as we keep this ratio above 1 (the horizontal line) we are generally making progress – although the higher we can get it the better.

You can download these seven graphs as slides here.

Note: The graphs in this article were produced using RStudio and the ggplot2 package. Graphs are exclusively based on publicly available Thembisa model outputs. Spotlight takes full responsibility for any errors or misrepresentations there may be in the graphs.

High price delays introduction of new TB prevention therapy

By Amy Green

Despite being an ancient disease, tuberculosis (TB) remains the world’s leading infectious disease killer from a single infectious agent. For decades effective preventive therapy has existed, but has not been widely used. Recent optimism about a shorter and safer form of prevention therapy has been dampened because of its high price. While price negotiations continue behind closed doors, Spotlight asks when this new therapy will become available in South Africa.

A quarter of humanity is infected with the TB bug, according to the World Health Organisation (WHO). If left untreated, TB infection can develop into active TB disease, the form of TB that makes people sick and is capable of being transmitted from one person to another.

Only a small percentage of infected people, up to an estimated 15%, ever progress from TB infection to active disease, but the rates are much higher in children as well as people living with HIV and other diseases affecting the immune system. South Africa’s high rates of HIV raise this risk tremendously.

Additionally, while the global levels for infection with the TB bug, known as latent TB infection, are high, they are much higher in South Africa. “More than half of the South African population has latent infection,” says Professor Harry Hausler, chief executive officer of TB HIV Care. “The idea is to treat this latent infection so that it doesn’t progress to TB, and the focus up until now has been on people living with HIV because of their higher risk.”

According to Lotti Rutter of Health GAP, an international HIV advocacy organisation with a presence in South Africa, despite the fact that “people living with HIV with latent TB infection are 21 times more likely to develop active TB than HIV negative people, and one third of all HIV-related deaths are due to TB, fewer than one million people with HIV were started on preventive TB therapy in 2017”.

A large proportion of these were in South Africa, mostly receiving the drug isoniazid. So-called isoniazid preventive therapy (IPT) has to be taken for anything from six to 36 months.

According to Deputy Director General at the National Department of Health (NDoH) Dr Yogan Pillay there was a slight increase in the number of newly diagnosed HIV patients started on isoniazid between 2017 and 2018: from 40 7602 to 48 4982.

A new TB prevention option

“Isoniazid preventive therapy is long in duration, carries a higher risk of liver toxicity and is less likely to be completed in full than novel therapies using the drug rifapentine,” says Rutter.

Rifapentine-based preventive therapy, commonly referred to as 3HP, only has to be taken for three months.

At a cost of $45 for the three-month course 3HP is widely considered to be unaffordable to most countries, including South Africa. The sole manufacturer, pharmaceutical giant Sanofi, has been in talks with global funders since 2017 to reduce the price.

The target price is $15 per course which has been deemed affordable to funders like Pepfar, a United States government funding mechanism, and Unitaid, a multilateral aid organisation. Earlier this year Pepfar indicated that they would be able to procure 3HP for their programmes at this, or a lower, price.

Citing University of Liverpool research, the New York-based health advocacy organisation Treatment Action Group (TAG) has argued the regimen could be sold for as little as $10 per course and still provide Sanofi with a reasonable return.

The negotiation process with Sanofi was kicked into action following a 2017 Unitaid grant for the IMPAACT4TB project which had a direct goal to lower the price of rifapentine and to foster generic competition to radically ramp up access to 3HP in high-burden countries.

Initial negotiations included Unitaid but after a generic manufacturer registered a 3HP product for WHO prequalification earlier this year, UNITAID decided it would make more sense to wait.

Spotlight has learned from two reliable anonymous sources that the manufacturer responsible for the generic, in the form of a fixed-dose-combination, is India’s Macleods Pharmaceuticals.

Macleods and other generic players will increase competition in the market and should in time bring down the cost significantly. Most countries, however, have to wait for the WHO prequalification process to conclude, with some like South Africa requiring registration with national medicines regulators, before they can begin procuring generic 3HP.

According to Professor Gavin Churchyard, chief executive officer of The Aurum Institute, South Africa will likely be one of the first countries in which generic manufacturers will register their 3HP options but “given how long it took for Sanofi to register 3HP locally – about two years – registration is not going to happen right away.”

The NDoH has placed rifapentine on tender and Sanofi has responded, according to Pillay, and currently the negotiations are happening between these two parties alone.

“Unitaid is open to procuring Rifapentine from Sanofi to facilitate 3HP introduction in early adopter countries before generic formulations come to market at scale, provided a reasonable price is offered. Several countries want to move with 3HP now. For South Africa, even if the first generic product receives prequalification in 2020, the duration of the national Health Products Regulatory Authority process would mean that it is unlikely to be available in South Africa before 2021,” says Unitaid’s director of operations Robert Matiru.
“We are monitoring the outcome of South Africa’s negotiations with Sanofi for a lower rifapentine price and feel it’s important that the final price is extended to other low and middle-income countries,” he said.

Additionally, in March the results of the DOLPHIN study were announced providing evidence that 3HP is compatible with the antiretroviral dolutegravir which Pillay said would be introduced as the first-line HIV treatment in South Africa on 1 September (initially set for 1 August). Previously, a small study had raised questions as to whether 3HP and dolutegravir could safely be taken together.

IPT for the time being

Locally, says Hausler, 3HP is only available on a miniscule scale at three demonstration sites. Instead, isoniazid is given to people living with HIV for a minimum of six months to a maximum of 36 months.

According to Churchyard, most people living with HIV in South Africa are prescribed isoniazid for a year, after active TB disease has been ruled out. Those in which latent infection has been confirmed are meant to take the drug for 36 months and a six-month course is given to people who have not started taking antiretroviral treatment.

Hausler explains that studies have shown that people living with HIV who have taken the full course they have been prescribed have been protected against active TB for up to three years.

One of the biggest problems with this regimen is the long duration of treatment and that very few patients who are started on the drugs actually complete the course, says Hausler.

Pillay told Spotlight that the treatment completion rates are “very low” but he was not able to provide concrete figures because “we do not monitor this.”
However, according to Hausler, the government does attempt to record this data but it is problematic. “At every patient visit, clinicians are meant to write down whether they received isoniazid or not and below 40% actually do. But we know that completion rates are low and definitely not where we want them to be,” he says.

The only quality data is on how many newly diagnosed HIV patients given ART are also given isoniazid, even though the current guidelines state that TB prevention treatment should also be offered to any HIV positive person as well as children under the age of five living in the same household as someone with active TB.

Guidelines to be updated

The NDoH is in the process of finalising new guidelines on preventive TB treatment which will extend its offering of isoniazid, as well as 3HP when it becomes available, to all household contacts of persons with active TB. At the moment only children aged five or younger and contacts living with HIV are eligible.

Pillay says that the guidelines are not, however, on the agenda of the next meeting of the National Health Council’s technical committee set for the first week of August and will only likely be discussed at the following meeting. These meetings generally happen every six weeks.

Hausler says that this is where 3HP will have most of its benefit over isoniazid. People already on daily drugs for HIV might not mind an additional pill for a year in the form of isoniazid, but HIV negative people might rather choose to take 3HP which is given once a week for three months.

“Intuitively, it’s hard for people to grapple with the concept of prophylaxis: taking drugs when they are not sick, to prevent and not to treat. So, a shorter course for these groups is very important,” he says.

Currently 3HP comes in the form of 10 pills per week which is a high pill burden for anyone, according to Pillay, who said that South Africa is hoping for the WHO to approve (pre-qualify) a fixed-dose-combination version as soon as possible.

In the meantime, activists are hoping for a quick resolution to the high cost of Sanofi’s regimen.

“Sanofi is not the originator of rifapentine. It’s an old drug and its primary patents have expired long ago. It came into their portfolio through decades-long pharmaceutical mergers and acquisitions,” explains TAG’s TB Co-Director Mike Frick.

“It is true that they have advanced its development and it’s not as though they haven’t been good stewards but the majority of the research was funded by the United States (US) tax payer. And the citizens involved in the trials pivotal for the formation of 3HP, not only in the US, but in countries like South Africa, don’t necessarily have access to rifapentine,” he says. “Considering the millions in public investment and the fact that the drug is old and has many public benefactors, the continued high price is really unconscionable.”

People: Face to face with Dr Bandile Masuku

By Biénne Huisman

New Gauteng MEC for Health Dr Bandile Masuku has had a long day, but it does not show. His voice is slow and thoughtful; his attire immaculate: shiny shoes and a navy cardigan, buttoned all the way. Behind spectacles his eyes are bright. ‘They’re Tom Ford. Yes, I’ve been colonised,’ he says, laughing.

Masuku’s new job is no laughing matter — of this he is well aware.

On May 28 he was sworn in as Gauteng’s new head of health, inheriting a department described by Premier David Makhura as ‘on its knees.’ This despite receiving the biggest portion — R50-billion — of the provincial budget.

‘It’s a daunting task,’ says Masuku. ‘You know, one of those key moments in your life.’

We’re inside a boardroom at the African Pride Irene Country Lodge in Centurion. Outside, an ANC caucus is underway.

Earlier today Masuku joined Makhura on a surprise visit to Mamelodi Hospital, in the Mamelodi township northeast of Pretoria. A video showing 76-year-old patient Martha Marais handcuffed to a bench at the hospital went viral on social media last month. The hospital has been under scrutiny since, with the South African Human Rights Commission stepping in.

Dr Bandile Masuku. Photo by Thom Pierce

‘People are saying Mamelodi is my fire baptism, and in a sense it is,’ Masuku says. ‘It combines all the problems we face in the department: staff shortages, bad staff attitudes, inadequate infrastructure, no appropriate equipment, cleanliness of hospitals.’ While speaking, he ticks off the challenges on his fingers.

‘I mean restraining in a medical ward, this is not something strange. But you cannot restrain a patient by cuffing her hand to a bench. No, we certainly don’t use handcuffs. Appropriate equipment and medicine is needed. A patient should be restrained on a stretcher or on a bed.’

Masuku says — as a starting point — staff morale will be addressed through a human resources programme to be rolled out at health facilities across Gauteng.

‘You know, bad staff attitudes don’t just happen because people are badly raised. So there would be factors that make them edgy; irritable, angry and fatigued. We have enlisted the help of a team who deal with staff morale, who are designing an intervention program. They call it “employee value proposition”. This will be put in place for all our administrators, for all our clinicians. The thing is we also need them to buy into it, to add onto it, so that it’s not just something that comes from the top. I think uplifting staff morale will change staff attitudes,’ he says.

‘We also have to improve training, you know. People need to be trained in customer care. And beside empathy and care, they must be trained in handling difficult situations; handling angry or violent or hostile patients.’

Filing is another pressing concern. ‘The issue of the filing system came up fairly sharply too. Many patient files have been lost. We really need to go electronic, digital. That will save a lot of time and a lot of space.’

Speaking of the Mamelodi incident, Masuku’s words carry the gravity of someone who has worked at the coalface himself. Indeed, he has practised as a doctor at hospitals around Gauteng: Charlotte Maxeke Academic Hospital, Chris Hani Baragwanath Hospital and Pholosong Hospital. His speciality is obstetrics and gynaecology. Right before his appointment, Masuku headed the obstetrics and gynaecology unit at Thelle Mohoerane Regional Hospital, in Vosloorus.

Masuku was born at Baragwaneth in Soweto 43 years ago. ‘So I ended up working the very maternity ward where I was born. I’ve come full circle,’ he says.

In Soweto, he grew up in a family of health workers. One of three siblings, Masuku was the middle child between two sisters.

‘I’ve always been surrounded by health workers,’ he says. ‘Two of my aunts were nurses and my paternal grandmother, well she was one of the first nurses in Soweto. Actually, she was in a class with Nelson Mandela. So it just came from there; their ability to have empathy, their ability to care and to do things for others, all of that played a great role.’

A bright youngster, Masuku excelled at school. ‘I didn’t even do standard four,’ he says. ‘Yeah, I was promoted. I got almost 100% in standard three, so went straight ahead to standard five.’

At Sekano-Ntoane Secondary School, he cut his political teeth at the Congress of South African Students (Cosas). This saw him detained, disturbing his preparations for matric in 1991. Not wanting to jeopardise his career, he repeated the year, matriculating again in 1992. ‘Because of my political activism, I repeated matric,’ he says. ‘My first matric mark was adequate, but not good enough for university and medical school. The second time went much better; I got an A for English, with my maths and physics marks much improved.’

In 1994, he enrolled for a BSc at Sefako Makgatho Health Sciences University in Pretoria, then known as the Medical University of South Africa (MEDUNSA); and in 1998 for a degree in medicine, completed in 2004. Again he repeated a year — 1999 — the year he served as president of the university’s Student Representative Council (SRC).

‘When I was SRC president,’ he says, ‘I didn’t attend any classes, even though I was expected to do so. While I wanted to be a doctor, I also had to fight for student rights and student grievances.’

Speaking to Masuku, it becomes clear that his ambition to become a doctor and his predilection to lead politically have always existed side-by-side, often clashing.

In 2002 he was elected to the national executive committee of the South African Students Congress (SASCO); and in 2013 he became national spokesperson for the ANC Youth League.

What drew him to obstetrics and gynaecology? Was it because he grew up in a family of women? He laughs. ‘Yes, it was a natural choice,’ he says. ‘My first time in a hospital as a medical student was in a maternity ward, I was in my third year. Then, when I finished my medical degree as an intern, my first block was in obstetrics, at Charlotte Maxeke. I fell in love with it — it felt like something I would love to do for the rest of my life. It combines being a doctor with a little bit of surgery. There is also the big satisfaction of having two patients in one — literally.’

On his own home front, Masuku has three sons. The youngest, born in the week of his inauguration, is but a month old. ‘No I am not getting much sleep,’ he says, smiling.

His wife of four years, Loyiso, is a local ANC councillor. The family lives in Alberton.

On his iPad, Masuku keeps mostly political books. He is a follower of Argentine revolutionary and physician, Che Guavara. ‘Most of my books and collections about Guavara are his thoughts about medicine,’ he says. Then there are the icons: Nelson Mandela, Oliver Tambo, Walter Sisulu and Steve Biko. His favourite book is Let My People Go by Albert Luthuli. ‘This is Albert Luthuli’s biography. Actually I think it’s one of the first books I really understood because I wrote an essay about it in my matric exam. The question was: “Tell us about a book you would advise all young people to read?” It summarises the history of our country, the history of our struggle and the basic principles surrounding it.’

Masuku likes to unwind watching soccer, especially at the stadium; with occasional bouts of rugby, cricket, boxing and Formula One support thrown in. ‘I used to play soccer,’ he says. ‘At varsity I even formed a team, it’s still there. But I’ve stopped, I felt that if I get injured now… My daily life really is a bit hectic, especially now.’

On average, Masuku’s days start early: he first reads on his iPad, then from six o’clock, he starts preparing for work. ‘It all depends on where I am supposed to be that day,’ he says. ‘I don’t go to the office much. I’ve been visiting a lot of facilities, doing unannounced site visits. For example, this morning I went with the premier to Mamelodi Hospital. He decided late last night that he needed to go over there himself.’

On the Life Esidimeni catastrophe, which saw at least 144 Gauteng psychiatric patients die after being transferred to inadequate facilities, Masuku says: ‘This is a very big tragedy for our country. We need to see this tragedy not repeating itself.’

‘Esidimeni gives us lessons,’ he adds. ‘In health, when errors happen, these adverse effects give us an opportunity to do things differently. When you understand the problem, it’s the first step to coming out with the right solution.’

According to Gauteng’s shadow health MEC Jack Bloom, of the DA, fifteen Esidimeni patients were still unaccounted for in May.

These are big challenges. In a show of humility, Masuku admits he will need help in his new role. ‘I don’t think with my own wisdom alone I’ll be able to do it,’ he says. ‘I will need a lot of help. I’m going to rely on people who also have experience in the field, and passion. Take for example the Treatment Action Campaign (TAC). These are people, ordinary people, who have a passion for how quality health care could be. And it’s not like they have all the answers, but they work with the people, they develop solutions with the people. They do not intend to solve everything at once, but they understand that there is a bit they can do. So us in government, we can use the strength of the TAC in terms of mobilising communities.’

Masuku says he has invited Bloom over for tea to discuss the portfolio. He has also approached the EFF and IFP for input.

‘What I’ve decided in my head is that I’ll give this my best shot,’ he says. ‘And I’m hoping that my leadership style, my ability to analyse the problem in a proper way will lead us toward something. I have a long history of board experience too, which also gives you a sense of governance.’

It may well be that Masuku’s new position as health MEC is the ideal culmination of his attributes and experience thus far, both as a medical professional and as a leader.

‘We need to change how we do things, improve how we do things,’ he says. ‘We need to achieve a new normal, you know. A level of efficiency that when you get used to it, it just becomes an everyday thing.’

He reiterates that Mamelodi Hospital will serve as the benchmark of his tenure. In fact, he insists that his progress at Mamelodi be assessed at premier Makhura’s State of the Province Address in February next year.

Fixing the public healthcare system in South Africa’s most populous province might well be one of the toughest jobs in the country. For now, Masuku’s frankness and his seriousness about the task at hand inspires cautious optimism. He might well be just the right person for the job. Time will tell.

Tuberculosis in SA: Three graphs that tell the story

By Sean MacDonell and Marcus Low

According to World Health Organization (WHO) estimates, South Africa continues to have one of the highest burdens of tuberculosis (TB) in the world. The burden of a disease refers to the number of infections and deaths within a population and the associated costs of treatment of a specific disease. Here we attempt to tell the story of the burden of TB on human life using several graphs. As the story of TB cannot be separated from that of HIV, we use estimates from both the WHO TB data portal and the Thembisa mathematical model of HIV in South Africa to examine trends in the data from 2000 to 2017. 

You can find more of Spotlight’s graphical storytelling on HIV here.

          1. How many people in SA get TB? 

The graph above shows the estimated number of TB cases per year in South Africa from 2000 to 2017. The solid red line indicates the median WHO estimate of the number of TB cases – these are the figures that are most commonly quoted. As you can see, the number of TB cases in South Africa is estimated to have been relatively stable from 2006 to 2014, peaking at approximately 500 000 cases in 2008, yet has decreased substantially since 2015.

The dashed lines on the graph represent the high and low bounds of the estimates (in technical terms the 95% confidence interval). The fact that these lines are as far apart as they are tells us that there is very significant uncertainty about these figures and that we should take the estimates reflected by the red line with a grain of salt. As you can see from the dashed lines, the number of TB cases per year may well have peaked in 2007 at nearly 700 000 or in 2011 at only 370 000 – with the limited information at our disposal we can’t be sure. 

All of the graphs below use the relatively uncertain WHO TB estimates and should likewise be taken with a grain of salt. 

          2. TB cases and HIV status

The graph above shows the number of new cases of TB per year in South Africa. The coloured regions divide the number of new TB cases by HIV status. Well over half of all people who develop TB are living with HIV, as you’d expect in a country where the TB burden is fuelled largely by the HIV epidemic. The total number of new TB cases peaked in 2008 and has since been declining – a decline that is linked to the increase provision of antiretroviral therapy. Providing people living with HIV with antiretroviral therapy makes it much less likely that they will develop TB.

           3. How many people die of TB in SA?

The graph above displays the number of deaths from TB, with the different colours once again representing the breakdown by HIV status. The large swath of purple clearly indicates the majority of deaths from TB have been in people who were living with HIV. Deaths from TB among HIV positive individuals peaked in 2005 at approximately 130 000. It has decreased dramatically since then primarily due to increased access to antiretroviral therapy. 

The downward trend in TB mortality among HIV negative individuals, however, has not been as dramatic and has stagnated in recent years. Mortality peaked in 2005 at 30 000 deaths and was estimated at 22 000 in 2017. The plateau in TB mortality for HIV negative patients suggests that we are not doing a particularly good job at treating and preventing TB specifically – and supports the suggestion that most of the progress we have seen against TB in South Africa is fuelled by the country’s impressive HIV treatment programme.

Note: The above graphs can be downloaded here for use in presentations. The graphs were generated in RStudio using the ggplot2 package. All the data used in these graphs are freely available from the WHO TB portal and the Thembisa model outputs linked to at the top of this article.

Welcome detail in Mpumalanga HIV and TB plan

The National Strategic Plan (NSP) for HIV, TB and STIs 2017 – 2022 is supposed to guide South Africa’s response to HIV and TB. While this national plan sets out broad targets and strategies, the implementation of this plan depends on provinces. To this end, each province had to develop a provincial NSP implementation plan (PIP).

Mpumalanga’s plan is called the Mpumalanga Provincial Implementation Plan for HIV, TB and STIs 2017 – 2022 (the Mpumalanga PIP). (Spotlight previously published analysis of the KwaZulu-Natal PIP.)

Broadly speaking, the Mpumalanga PIP stands out for including a series of well-chosen concrete implementation targets. While most provinces include targets in their plans, targets tend to be broad and to relate to indicators such as new HIV infections, rather than to the specific interventions that will help reduce new HIV infections. Mpumalanga is thus one of the relatively few provinces whose implementation plan goes beyond just broad statements of intent and engages seriously with implementation. Below we analyse the PIP more closely. 

The context

Around 7 100 people died because of HIV in Mpumalanga in 2018. This is much lower than the peak of 31 000 in 2006. Around 19 300 people became HIV positive in the province in 2018. Since more people are becoming infected than are dying, the absolute number of people living with HIV in the province is still rising.

As in other provinces, the dramatic decline in AIDS deaths is driven by the increased availability of antiretroviral therapy. By 2018 there was in the region of 470 000 people on treatment in the province – more than ten times as much as 10 years ago. 

Around 700 000 people in the province are living with HIV – This amounts to 15.4% of the population. This makes Mpumalanga the province with the second highest HIV prevalence in the country behind only KZN.

Regarding the first of the UNAIDS and NSP 90-90-90 targets, Mpumalanga is tied with the national estimate of 90.5% of people living with HIV knowing their status. Regarding the second 90 – percentage of diagnosed people on treatment – Mpumalanga is estimated to be on 73.5%, ahead of the national estimate of 68.4%. On the third 90 – percentage of people on treatment who are virally suppressed – Mpumalanga is on 88.1%, just below the national estimate of 88.4%. (This is using the UNAIDS definition of <1000 RNA copies/ml – <400 RNA copies/ml is also used sometimes).

While the performance on the 90-90-90 targets is decent when compared to other provinces, it should be considered in the context of the province’s extremely high HIV prevalence. In this light it is at least as urgent in Mpumalanga as elsewhere to improve on the second 90 by taking concrete steps to help more people to start treatment and to stay on treatment.

The Mpumalanga PIP

As with most PIPs, the Mpumalanga PIP contains useful information on the state of the HIV and TB response in the province. Various problems in the response are identified, often with specific districts or sub-districts identified as focus areas. Two of the province’s three districts, Gert Sibande and Ehlanzeni, are of the hardest hit by HIV and TB in the country. 

In some instances the PIP’s recognition of the problems in the province is refreshingly frank and honest. In relation to TB it states: “The provincial challenges to address mortality and morbidity were largely linked to inaccessible TB treatment services due to drug stockouts, inadequate care provision and poor adherence models.”

Like most PIPs, the Mpumalanga PIP is good on the broad solutions. For example, in relation to TB screening it states: “Testing for TB will be intensified at facility level to amplify TB case finding in high burden areas such as mines, correctional services, mining communities, etc. A provincial drive to promote household symptom screening and the use of a combination of Xpert MTB/RIF and culture tests will be initiated. Ward-based outreach teams will be used to initiate TB positive clients on IPT (TB preventive therapy) and track and trace TB contacts.”

As a general statement on TB detection and TB prevention this ticks many of the boxes one would want to see ticked in the PIP. 

So far, so good. But implementation plans need to go beyond such broad statements of intent if they are to have any impact on implementation. The KZN PIP, for example, generally does not – fortunately the Mpumalanga PIP often does.

More detail than most

A problem with some PIPs is that it sets targets to reduce new HIV infections but does not contain much planning on how the reduction will be brought about. While the Mpumalanga PIP suffers from this to some extent, it also contains some well-chosen targets that get at the “how” and not just the “what”.

So, for example, the Mpumalanga PIP contains a target to increase the number of facilities providing voluntary medical male circumcision in the province from 64 to 85. This may not seem a particularly ambitious target, but it is achievable and provides a concrete means by which to reduce the rate of new infections in the province. In addition, the Department of Health is identified as being responsible for meeting this target. Ideally, the Provincial AIDS Council will ask the Department of Health to report on their plans and progress in this regard every time the council meets. Since it is such a clear and simple-to-track indicator, the Department of Health can have no excuse for not reporting.

Similarly, the PIP sets a target of increasing the number of youth and adolescent friendly accredited healthcare facilities from two to 36 over the period of the PIP. Again it is a concrete and implementable target that the Department of Health can be held accountable for. As discussed later in this article, the PIP falls short in other respects when it comes to young women and girls, but this target at least proposes another concrete and measurable intervention.

But some short comings

The Mpumalanga PIP nevertheless leaves some crucial areas insufficiently addressed. Despite a professed focus on HIV prevention and a “substantially stronger focus on adolescent girls and young women” there are no specific targets on providing PrEP and the condom distribution targets are roughly in line with current levels and does not include the specific targeting of young people and the provision of condoms at schools. Instead, the PIP’s focus is on incremental improvement of interventions that are already being implemented.

This tendency not to contain much ambitious thinking beyond the status quo is unfortunately very common in provincial planning. One can only speculate, but it seems likely that this relative conservatism is due to the relative weakness of civil society representation in many PIPs – which often means PIPs end up reflecting the trajectory government is already on. Ideally though, forums like AIDS councils and planning documents like PIPs should be places where civil society can pressure government to be more ambitious in its response to HIV and TB.

In addition, while the PIP proposes various useful interventions, it arguably relies too heavily on community dialogues and other forms of meetings. Dialogues are important, but, once you have empowered people with information you need to back it up with concrete interventions such as the provision of PrEP or condoms.

As in other provinces, there are questions to be asked about the implementation of the PIP. Two years into the plan, the PIP has not yet been costed – although we understand that a costing is in progress and should be completed soon. Questions we sent the contact person for the Provincial AIDS Council regarding the finalisation and adoption of an M&E framework for the PIP went unanswered.

Finally, the PIP states: “The province will develop a Provincial Social and Behaviour Change Communication Strategy under the leadership of the department of Social Development in order to assist individuals and communities to implement communication strategies that reduce HIV, TB and STI risk behaviours.”

We asked the Provincial AIDS Council’s contact person whether the communications strategy has been developed but received no answer despite various follow-ups.

The way forward

With a costing expected soon and with a number of useful indicators, Mpumalanga has some of the building blocks in place that can set the stage for real progress against HIV and TB in the province. Whether or not this potential is realised will depend largely on whether or not the political will exists in the province to make implementation of the PIP a reality and to improve the functioning of the public healthcare system.

Mpumalanga faces severe HIV and TB epidemics and, as with a number of other provinces, is struggling with widespread dysfunction in the public healthcare system. The challenge ahead of Premier Refilwe Mtsweni and MEC for Health Sasekani Manzini to build a more capable state in the province is daunting.

Arguably the most critical element of this challenge is to ensure enough appropriately qualified healthcare workers and other staff are employed in the province’s public healthcare system. The PIP has the following, among others, to say about the province’s human resource needs:

  •  “Given the ambitious nature of the PIP’s service targets and the imperative to expand efforts to address social and structural drivers, human resource needs under this PIP undoubtedly will grow and further diversify.”
  • “The PIP requires an increase in the number of primary health care nurses who have the skills to administer antiretroviral therapy, manage drug-resistant TB, and address STIs beyond syndromic management, as well as a sufficient number of doctors to support services.”
  • “Linking with national processes that facilitate the formalization of community health workers as a cadre, appropriately trained and supported, and fully integrated into the various systems would be critical.”
  • “Under this PIP, Mpumalanga will invest more resources and effort in the training and mobilisation of peer educators, lay counsellors and support personnel.”  

Maybe the biggest question facing healthcare in Mpumalanga, and the question upon which implementation of the PIP hinges, is whether the necessary investments of funds and political capital will be made to meet these human resource requirements in a way that is sustainable.

Note: Figures used in this article are taken from the recently published Thembisa 4.2 model outputs. Thembisa is the leading mathematical model of HIV in South Africa.

Limpopo to release health workers despite massive shortages

Whistle blowers have alerted the Rural Health Advocacy Project to a decision by Limpopo’s Health Department (LDoH) to release provincial bursary holders from their contractual obligations. RHAP has in its possession a letter circulated to health professionals inviting them to a meeting to discuss the decision which will affect approximately 540 health professionals who have received funding from LDoH. The affected health professionals include medical doctors, professional nurses, pharmacists and allied health professionals (occupational therapists, physiotherapists, speech therapists and audiologists.)

The decision to release the bursary holders from their Bursary Contractual Service Obligations will have severe implications on health service delivery and does not ensure the protection of the core right to health. It will ensure that the reported ratios of 10 pharmacists per 100,000 people will not improve nor will the 3 physiotherapists and occupational therapists, respectively, per 100,000 people, thus underservicing the population in Limpopo and failing to progressively realise the right of access to health care services.

The LDoH has under half (47% – 33,848 of the 63,460 posts) of the personnel it requires to function effectively. To fix the broken provincial health system, LDoH developed a Recruitment and Development Strategy (“Strategy”) to formalise the bursary scheme and ensure that it can attract and retain health professionals. The Strategy is also intended to address some of the factors that result in the high attrition rate, these include a lack of opportunities for career-pathing, inadequate infrastructure, inadequate and non-functional equipment as well as poor working conditions.

It is therefore counter-productive that the LDoH, which has historically suffered from low healthcare worker figures would opt to let go of 540 health professionals whose services are obviously needed. Typical rhetoric would lay blame on the economic recession and austerity measures taken by state departments. However, we should be wary of austerity being the catch-all net for all decisions that fail to meet the Constitutional standard envisioned in section 27 of the Constitution. The International Covenant on Economic, Social and Cultural Rights (ICESCR) to which South Africa is a signatory is explicit when it comes to austerity. It cites the implementation of austerity measures may only be justified when a) less restrictive measures have been exhausted, b) austerity measures must be temporary and that any other course of action would be more detrimental to the realisation of rights and that c) they cannot be intentionally or unintentionally discriminatory, amongst others.

In late 2018, President Ramaphosa released a Stimulus Package for Health. This constituted a significant boost of 5300 posts (clinical and support staff) into the public health system distributed across all 9 provinces. The LDoH, in particular, received 227 medical officer posts (for post-community service doctors), 68 pharmacist posts, 309 professional nurses’ posts and 57 allied health professional posts. A total complement of 701 new posts were funded, in addition to the number already budgeted for by the LDoH. It is curious that a decision to forego the services of 540 health professionals be implemented with such haste. Surely, the lack of available funding was anticipated earlier in the year. If so, a large portion of the 701 new posts could be used to offset the 540 posts that will be lost. There has been no information on how many of the posts created by the Stimulus Package have been filled.

We are also unsure how the LDoH intends to staff the state-of-the-art central level hospital whilst failing to adequately implement its Strategy and retain 540 skilled and willing health professionals whose studies the LDoH has already funded. The current state of Primary Health Centres (PHC) and district level hospitals also leaves much to be desired and it does not seem that this decision will improve services at these facilities.

Only 25% of Limpopo’s clinics meet ideal clinic status, the second lowest of all provinces, competing for last place with the Eastern Cape; another predominantly rural province. Spending by LDoH shows a strong focus towards district hospitals. Consequently, it would appear that the bulk of health services are provided at this level. Over the 2017/18 period, 51.3% of District Health Services was spent on district hospitals. However, this contrasts starkly with the investment in PHC services with Limpopo being the lowest spender in the country. Over the 2017/18 period, per capita spending on PHC was R352, which is almost R100 less than the national average. And therefore, incongruent decision making and spending is not isolated solely to the 540 health professionals who are soon to lose their jobs but rather is characteristic of Limpopo Department of Health. The investment in the studies of 540 health professionals to improve health services in Limpopo will be lost to other provinces or the private sector.

Due consideration must be given to the inherent challenges that rural provinces, such as Limpopo, face. The government must take into account factors such as low population numbers that are spread across large areas and resultant diseconomies of scale which make providing services to these provinces more expensive, and budget accordingly. The users of the healthcare system will bear the brunt of the loss of personnel most and the figures reported by LDoH will not allow for increased access to health care services.

There is contradicting information on the number of posts in LDoH and the number which has been filled and how many remain vacant. There has been no explanation as to how the LDoH funds bursary holders but fails to ensure that there is funding for their posts in order for them to continue working once after their community service. There are also no reports on the progress in implementing the Strategy.

As a coalition of social justice organisations committed to the protection and advancement of socio-economic rights, we appeal to:

  • the Minister of Health to support the development of costed provincial Human Resources for Health plans that consider the varied implementation contexts in different provinces;
  • the Minister of Finance to consider rural adjustments starting with HRH to be included in Equitable Share Formulas;
  • the Premier of Limpopo to amend the framework that informs how the province distributes its unconditional provincial equitable share allocation in order to increase the portions dedicated to health and education.
  • the MEC for Health and the administrative heads of health to work together to ensure that the decision to release bursary holders is reversed in order to fulfil their Constitutional obligations of ensuring access to health care services so that the wellbeing of the people of Limpopo is placed at the centre of all decisions.

This open letter has been endorsed by the following social justice organisations:

RHAP, SECTION27, the Treatment Action Campaign, People’s Health Movement, Rural Rehab South Africa, Rural Doctors Association of South Africa, Institute for Economic Justice.

KZN’s HIV and TB plan: Good on structure, low on detail

The National Strategic Plan (NSP) for HIV, TB and STIs 2017 – 2022 is supposed to guide South Africa’s response to HIV and TB. While this national plan sets out broad targets and strategies, the implementation of this plan depends on provinces. To this end, each province had to develop a provincial NSP implementation plan (PIP). KwaZulu-Natal’s (KZN) PIP is called the Multi-Sectoral Response Plan for HIV, TB and STIs for KwaZulu- Natal Province 2017-2022 – but in this article we will refer to it just as the KZN PIP.

Broadly speaking, the KZN PIP’s engagement with the governance and consultative structures required to implement a plan like this is refreshingly realistic and shows an awareness of the very real risk that PIPs can become inconsequential processes parallel to existing government planning processes. The plan also does a good job of using data to define the particular problems in the province and flagging, in general terms, the kind of interventions that are required. Unfortunately, the KZN PIP is very low on detail when it comes to implementation – which is deeply disappointing in an implementation plan.

Some context

KZN is at the epicentre of South Africa’s HIV epidemic, if not the world’s. Annual AIDS deaths in the province peaked at 87 000 in 2005 and fell to around 17 000 in 2017. In 2019 there was probably around 15 000 deaths, although there is significant uncertainty regarding the 2019 figures. The decline in AIDS deaths in the province is driven largely by the provision of antiretroviral therapy – in 2005 there were 27 000 people on treatment in the province, today there is around 1.4 million.

One major concern however, is that growth of the HIV treatment programme in the province has slowed significantly in recent years. In 2014 around 230 000 people in the province were newly started on treatment. That number has dropped every year since and is now estimated to be under 100 000.

While AIDS deaths have declined dramatically, the rate of new HIV infections remains stubbornly high in the province. While the estimated 61 500 new infections in 2017 is much better than the 160 000 per year seen around the turn of the century, it is nevertheless high and means that the absolute number of people living with HIV keeps going up. Just over a third of the new infections in 2017 (around 21 000) were in women and girls aged 15 to 24. Around two million people in the province are living with HIV.

The KZN PIP

Probably the most important target in the KZN PIP is to reduce new HIV infections to below 20 000 by 2022 – roughly a third of 2017 levels. Modelling suggests that this very ambitious target will not be met and that by 2022 levels would still be in the high 40 000s. According to the PIP “interventions revolve around expanded and intensified provision of biomedical services, sexual and reproductive health and the provision of pre-exposure prophylaxis to high risk groups.”

While specific mention of PrEP is welcome, the PIP rather confusingly says that PrEP should be provided “as part of a prevention package for the general population and key population groups e.g. sex workers” and elsewhere it refers to providing PrEP to “high risk groups”. Who exactly should be offered PrEP is never made much clearer than this. The plan does not specifically set out to provide PrEP to women and girls aged 15 – 24, as one might expect given the high infection rate in this group. It also doesn’t set any concrete targets or make any meaningful commitments regarding PrEP.

Some might argue about the cost effectiveness of PrEP, but even if the cost-effectiveness case is not as strong as that for say medical male circumcision, one could argue that the state has an obligation to nevertheless provide young women and girls at very high risk of contracting HIV with the means to protect themselves. Either way, if ambitious PrEP targets were rejected based on cost-effectiveness grounds, then the PIP should state that explicitly.

Given the high rate of infection in young women and girls, one would also expect a strong focus on the promotion of safe sex and condom use. As is recognised in the PIP: “While the province achieved its condom distribution targets, these were not adequate when calculated at number of condoms per eligible male.” One would expect such an admission to result in ambitious new condom distribution targets. Maybe more importantly, given the high rates of HIV in young women and girls, one would expect an unequivocal commitment to making condoms available at schools. Yet, while the PIP does not prohibit it, it certainly does not make a strong case for increased condom distribution or making condoms available in schools.

DREAMS and various specific interventions are mentioned, but unfortunately the KZN PIP does not break any new ground in plotting how the province will address HIV infection in young women and girls.

Touches on key issues

Though lacking in detailed planning and concrete commitments, the KZN PIP does nevertheless touch on a lot of the key interventions required at this stage of South Africa’s response to HIV and TB and provides useful district by district breakdowns of some key indicators. It is to be welcomed, for example, that HIV self-testing and same day initiation are both endorsed. With some help and guidance from national or the province, these are issues that districts can run with.

While increased testing is relatively easy to do, many other interventions require the province to play a greater role and for districts to be given more guidance. The KZN PIP could, for example, have set targets for how many adherence clubs would be needed in each of the province’s districts and included an estimate of the additional human and financial resources that would entail. Without such guidance and support from a provincial level, many of the good things mentioned in the KZN PIP might not be implemented, or not be implemented with sufficient ambition. It could be that these issues will happen through other channels, but the PIP should at least contain some thinking on it if it is to meaningfully impact implementation.

The PIP identifies some serious problems in the province’s HIV response. For example, it states that “information indicated that only 55.7% of those on ART had viral loads done”. Identifying and admitting problems like this is positive. It is not clear however from the PIP what will be done to address this problem. Ideally, a serious problem like this would have triggered the commissioning of research to understand why viral load testing rates are so low – and that research would then have been used to inform the PIP.

Reduce TB incidence by 50%

The KZN PIP sets a target of reducing TB incidence by 50% by 2022 when compared to 2017 levels. According to the KZN PIP: “Currently TB incidence is way above the World Health Organisation threshold of 200 per 100 000 population. Earmarked interventions relate to increasing the uptake of TB preventive therapy using various strategies including mass screening.”

The PIPs endorsement of interventions like mass TB screening and intensify contact tracing is to be welcomed. But whereas the intent is good, the lack of actual planning here too is concerning. There is no sign in the KZN PIP of serious engagement with the human resource requirements of expanding screening and contact tracing – and without the people to expand these services the expansion simply won’t happen. We had similar concerns with the NSP at a national level. The explanation then was that this kind of grappling with the nitty gritty of implementation would be addressed in the PIPs.

It is true that the KZN PIP does include a matrix of which departments and sectors or organisations would be responsible for various interventions, but it does not go much further than this. The background is good, the general ideas are good, but in the final analysis there is no real plan to implement.

Serious about structure

Some of the short comings with the KZN PIP outlined above might be explained by the disconnect that often exists between AIDS council and Department of Health planning processes. An AIDS council might set laudable goals, but the Department of Health controls most of the relevant resources. For this reason, the NSP and PIPs should ideally be taken into account in departmental planning processes and budgets. The odd thing is that, unlike most provinces, KZN seems actually to have put some real effort into making these various processes talk to each other. In fact, much of the KZN PIP engages with just this kind of structural problem.

The PIP states: “This plan has to the extent possible incorporated issues relating to HIV, TB and STIs as mentioned in other departmental and sector plans to enhance mainstreaming and multi-sector participation. It further presents a platform for participation in the response by departments and sectors that may not have HIV, TB and STIs activities in their current plan. They should use this plan as a reference document to inform their implementation in line with the departmental mandate. The activities can then be incorporated into departmental strategic plans when the opportunity arises.” And, “The PCA through its secretariat will be required to facilitate the process of ensuring that all departmental plans support the goals and objectives of this plan.”

The above should be in every PIP – with a premier using his or her clout both as premier and head of the PCA to enforce it.

In KZN the Premier has for years been chairing the Provincial AIDS Council and Spotlight sources report that the council meets regularly and is functional. In addition to the PCA, the PIP indicates that the province has 11 District AIDS Councils and 43 Local AIDS Councils. It seems however that leadership at PCA level has not filtered down. The PIP itself states: “While functionality of the PCA was impressive, that of AIDS Councils at the other spheres of government was generally poor especially, at local municipality and ward level. In some cases ward AIDS Committees were non-existent. More broadly all AIDS councils face the challenge of effective stakeholder participation with few stakeholders from different departments, organisations and civil society participating in AIDS councils. This affects governance and mutual accountability of the response.”

The problem of ensuring greater functionality at district or local AIDS council level is certainly not unique to KZN. It is also not something that can be solved in a PIP. For it to be flagged and grappled with in a PIP is welcome.

According to the KZN PIP “6 districts and 21 local municipalities had AIDS coordinators that were exclusively assigned to HIV.” Ideally all districts will have such AIDS coordinators, and all district-level councils will be chaired by mayors.

The plan also shows a good understanding for the fact that health crises of the scale of HIV and TB cannot be stopped by the Department of Health alone. It reads: “Government organisations, non-government organisations, civil society, the private sector, development partners, traditional leadership and the religious sector all have individual and complementary roles in implementing this plan and ensuring delivery.” It is arguably at district and local level that these “individual and complementary roles” are most important. More guidance on how to turn these good intentions into actual shared programmes and shared responsibilities may be useful.

 

No costing and no communications strategy

 

One area that the PIP gives a lot of attention to is communications. It goes as far as to commit that a “comprehensive provincial multi-media HIV, TB and STIs communication strategy will be developed”. This strategy is mentioned time and time again in the PIP in different contexts and in relation to various specific interventions.

The idea of a single communications strategy around HIV and TB in the province is not a bad one. While some HIV communications projects in South Africa have had only limited success, that is not to say that a properly conceived and executed strategy might not be more successful in KZN.

Unfortunately, according to Bonolo Pududu of the HIV and AIDS Directorate in the office of the KZN Premier, by mid-2019 this communications strategy has not yet been developed.

Another concern is that by mid-2019 the KZN PIP, which is a 2017 – 2022 plan, has not been costed. According to Pududu, this is not the province’s responsibility. “The costing of the Provincial Implementation Plans (all provinces) is/was the responsibility of national (i.e. SANAC),” says Pududu. “Initial processes commenced to cost the plans, however, the finalisation of this process is yet to be communicated.”

The PIP refers to a monitoring and evaluation framework document. A draft of this framework was shared with Spotlight. According to Pududu, “final consultations” with “provincial stakeholders” have not yet taken place and the PCA has not yet adopted the framework.

The lack of a costing of the PIP, the fact that the communications strategy has not been developed, and the fact that the M&E framework is only now being adopted are all worrying signs.

Though the KZN PIP is low on detailed plans, there is also some indication that some of the good things in it are not being implemented. Under goal 4 “Social and structural drivers” the PIP sets out to “implement and scale up a package of harm reduction interventions for alcohol and substance use”. Yet, for much of 2018 a needle-exchange programme in Ethekwini was shut down by the authorities, ostensibly because needles were not being disposed of appropriately.

What is to be done

With a new Premier in the province and a new MEC for Health, there is significant potential for change in KZN. The various good things in the PIP can and should be built on.

Ensuring district and local AIDS councils meet and are given sufficient guidance is one urgent priority. Making this happen will require strong political leadership together with clear thinking on what roles district and local AIDS councils can and should play.

A second urgent priority would be to flesh out some of the ideas in the KZN PIP into fully fledged implementation plans. How should new infections in young women and girls be addressed? Should the province embark on a massive scaling up of PrEP for young women and girls? Should there be a new safe sex and condom distribution campaign? Will these campaigns be funded and who will implement them?

Thirdly, whatever revised plan is made must be costed and, if a communications strategy remains central to the plan, then such a plan must be developed. If the PCA and the Premier is serious about the KZN PIP, then they must show that seriousness by executing the plan and integrating it into government planning and service delivery in the province.

Note: The KZN PIP uses estimates from the Thembisa model version 3.2. In this article we use more recent estimates from Thembisa version 4.1.)

 

 

New HIV estimates shows too many people are still not on treatment

South Africa has made great strides in scaling up HIV testing and increasing HIV suppression in patients receiving antiretroviral treatment (ART), but is still struggling to reach ART coverage targets and is falling short of HIV prevention goals. This is according to new findings from the Thembisa model of HIV in South Africa presented today at the 9th South African AIDS Conference held in Durban.

Overall, the model estimates that in 2018 there were 7.39 million people in South Africa living with HIV – equivalent to 12.9% of the population”, said a press release from the University of Cape Town. Around 4.57 million of these were receiving ART.

Around 80 000 people are estimated to have died of AIDS in South Africa from mid-2017 to mid-2018.

Progress against 90-90-90

The model painted a mixed picture regarding South Africa’s progress against UNAIDS and National Strategic Plan (NSP) targets of diagnosing at least 90% of people with HIV, treating at least 90% of those diagnosed with HIV, and achieving suppression of the virus in 90% of those on treatment (the so-called 90-90-90 targets).

According to the model around 90.5% of people living with HIV in South Africa have received a positive HIV diagnosis, 68.4% of those diagnosed are receiving treatment, and 88.4% of those treated had viral suppression (according to the UNAIDS definition of <1000 RNA copies/ml – <400 RNA copies/ml is also used some times).

Of all people living with HIV in South Africa (including undiagnosed cases and people not on treatment), only around 54.7% are virally suppressed. This figure is important since people with viral suppression do not transmit HIV.

Still too many new infections

Although South Africa has been making progress in reducing the rate of new infections, the statement expressed concern that the progress may be too slow. “Over the period from mid-2017 to mid-2018, Thembisa estimates there were 249 000 new HIV infections in South Africa – a 36% reduction on the 388 000 new infections that occurred between mid-2010 and mid-2011. However, the UNAIDS target is to achieve a 75% reduction in the annual number of new infections between 2010 and 2020. To meet this target, South Africa would need to reduce its annual number of new infections to less than 100 000 within the next year, which appears unlikely given the slow pace of decline to date.”

Dr Leigh Johnson, lead developer of the Thembisa model, identified two factors that were hampering progress towards the HIV incidence reduction target: “Firstly, ART coverage is lower in South Africa than in other southern African countries, and we need to do better in linking HIV-diagnosed individuals to care and retaining them in care. Secondly, there is increasingly strong evidence of reductions in condom use, relative to the levels we would expect in the context of high levels of HIV diagnosis.”

The model estimates that adolescent girls and young women (ages 15-24) account for 31% of all sexually-acquired HIV infections. It is estimated that around 22% of women and girls in this group used condoms the last time they had sex. This percentage appears to have been falling steadily from a high of around 30% in 2005-2007.

Although the rate at which new infections is coming down is too slow, the statement points out some success stories. “KwaZulu-Natal, the province with the most severe HIV epidemic, has succeeded in reducing its total annual number of new infections by 49% over the period from 2010-11 to 2017-18. Thembisa also estimates that the annual number of new infections in children declined from 29 000 in 2010-11 to 13 000 in 2017-18, a reduction of 55%.”

Apart from a variety of other sources, the latest version of the Thembisa model also takes into account data from the 2016 Demographic and Health Survey. Work on the model is funded by UNAIDS and from 2017 Thembisa has been the source on which official UNAIDS estimates for South Africa are based.

Spotlight will in the coming weeks be publishing more in-depth analysis of the new Thembisa estimates.