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.

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.”

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.

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.)

 

 

Minister: We must have communities, especially people living with HIV tell us what is needed

ADDRESS BY THE MINISTER OF HEALTH DR ZWELI MKHIZE AT THE OPENING OF THE 9th SOUTH AFRICAN AIDS CONFERENCE

INKOSI ALBERT LUTHULI INTERNATIONAL CONVENTION CENTRE, DURBAN, KWAZULU-NATAL

11 JUNE 2019

Programme Director

The Conference Chair, Prof Refilwe Phaswana-Mafuya

Premier of the KwaZulu-Natal, Mr Sihle Zikalala,

Ministers, Deputy Ministers and MECs present

The Mayor of eThekwini, Ms Zandile Gumede and other leaders from the local government

The UNAIDS Deputy Executive Director, Dr Shannon Hader,

Representatives of Multilateral and Bilateral Development Partners

SANAC Trust Board members

The Deputy Chair of SANAC and Chair of the Civil Society Forum, Ms Steve Letsike and other Civil Society Leaders

Senior Officials

Scientists, Researchers and Activists

Distinguished guests

Ladies and Gentlemen,

We meet during Youth Month, a few days before June 16th – a historic day in history of our country when thousands of young people took on the might of the apartheid regime. We salute the youth of 1976 and all young people who fought against the evils of oppression and we thank those that paid the ultimate price that they paid for our freedom.
Unfortunately, since then too many young people have succumbed to a preventable disease – HIV and AIDS! Every year for the past 9 years, South Africans gather here in the ICC to discuss ways to prevent HIV transmission as well as how to ensure that we initiate and keep people who are living with HIV on treatment.
The theme of this year’s conference is: Unprecedented Innovations and Technologies: HIV and change. Lest we forget, we have an estimated 7.1 million South Africans who are HIV positive with 4.6 million on treatment. This means that we must move rapidly to ensure that everyone living with HIV is on treatment. Equally we must ensure that those of us who are HIV negative remain negative! This needs innovation and change as the theme of this conference suggests!
For such a conference to succeed in its objectives we must have communities, especially people living with HIV tell us what is needed, researchers and scientists tell us what works and what does not work and government and its implementing partners who are implement with a great sense of compassion, passion and urgency all working together to defeat this epidemic!
This conference epitomises collaborative excellence where science, activism, government, and medicine come together in our responses to the HIV/AIDS epidemic and its twin – tuberculosis. This community has again come together, during this week, to rise to the enormous challenges the response to the epidemic continues to require. These include:
• The eradication of stigma and discrimination around HIV and calling out the prejudice that has fuelled it;
• The hard work of research and of ensuring that the research is relevant, puts the rights of people first and community voices are heard when planning and implementing the research;
• And importantly to ensure that government and its partners are responsive to the epidemic and that programmes are implemented effectively, efficiently and with quality.
This conference is where we dedicate our energy to share innovative plans to end the HIV epidemic. Today, we also pay tribute to the researchers and activists who have devoted their lives to finding solutions to end AIDS as a public health threat. In addition, we are reminded of the bravery and courage of late activists like Gugu Dlamini, Nkosi Johnson, and Prudence Mabele, who fought from the front to ensure that this epidemic does not define our destiny as a country. This day also brings to memory our global icon and the first President of democratic South Africa, Tata Nelson Mandela – who fought against the discrimination of people infected with HIV and TB and rallied behind the campaign for expanding ARV treatment.

Such gatherings remind us that we need to understand the needs of the person who lacks access to information and services so that we can provide them with information and services, including key populations, the LGBTI community, rural communities and people living with disabilities. These gatherings also remind us to harness the huge potential of people living with HIV to guide the response and delivery of services and the campaign against stigma and discrimination. The day also reminds us to create platforms for young people to shape and direct the programmes that are meant to empower them to stay HIV free and for those that are infected to live longer and reach their full potential so as to contribute to the development of the country.

Although our country is applauded globally for having progressive legislation and policies that promotes access to health services, evidence has identified stigma and discrimination, including self-stigma, and the negative attitudes of healthcare workers, as key barriers to accessing HIV and TB services.

The 2014 People living with HIV Stigma Index Survey, conducted by SANAC in partnership with the National Association of People living with HIV and AIDS (NAPWA), the Treatment Action Campaign (TAC and Positive Women’s Network (PWN), found the following:

• Over one-third of respondents (36%) reported experiencing some form of stigma in either their personal or social environments, including being gossiped about, experiencing verbal and physical harassment and assault.
• That over one-third (36%) of respondents reported being teased, insulted or sworn at because of their TB status.
• 27% harboured feelings of uncleanliness or dirtiness in relation to their TB diagnosis.
It is not surprising that people are discriminated against because they have tuberculosis – even though TB is a very old disease and has been around for hundreds of years – because it is airborne and anyone can contract TB.

A more recent survey, in 2018, conducted by the University of KwaZulu-Natal also found that stigma and discrimination affected access to health care services, creating barriers to access to and adherence to ART and deterred individuals with TB from accessing services for fear of breaches of confidentiality.

Let me be clear as the newly appointed Minister of Health, stigma and discrimination has no place in the provision of health services. We will take action against any health professional that discriminates against anyone on the basis of their illness, gender orientation, social status or any other characteristic!

In addition, to address these issues and to give effect to the objectives of goal 5 of our National Strategic Plan for HIV, TB and STI 2017-2022, I am pleased to announce that we have just launched a 3-year Human Rights Plan for HIV and TB, which aims to set out a comprehensive response to human rights and gender-related barriers to HIV and TB services in South Africa for people living with HIV, people living with TB, and vulnerable and key populations. This plan will focus on the following:

1. Stigma and Discrimination reduction
2. Train health and other frontline workers to provide care that is non-discriminatory
3. Sensitize and train Law makers and law enforcement agencies
4. Campaigns that focus on legal literacy and rights
5. Strengthening legal support services
6. Monitoring, reviewing laws and policies
7. Reducing gender inequality and gender based violence

I would like to take this opportunity to thank the SANAC Human Rights and Legal Task team under the leadership of the Deputy Minister of Justice, Mr John Jeffrey for overseeing the development of this plan. In working with the Chairperson of SANAC, I will ensure that the implementation of this plan becomes a standing item in all SANAC InterMinisterial committee meetings and in SANAC plenary meetings.

The response to the HIV and TB epidemics needs resources. We are grateful that our government is the main funder of our responses. In addition, we wish to thank the Global Fund for their support which was recently announced ($369 million over the next three years) and the President’s Emergency Fund for AIDS Relief (PEPFAR) which will provide $730 million in funding in the 2019/20 financial year. I want to encourage everyone that benefits from these funds to ensure that the funds are used as effectively and efficiently as possible. We have to use these scarce resources to reach the target that President Ramaphosa announced in the 2018 State of the Nation Address of 6.1 million people living with HIV on treatment by December 2020! We dare not fail to achieve this target if we wish to reach epidemic control!

In closing, I would like to thank the Conference Planning Committee under the leadership of Prof Refilwe Phaswana-Mafuya for all the hard work of planning such a big conference and wish everyone fruitful deliberation over the next 3 days.

I thank you.

The TB in the air we breathe

Wedged between mountain and sea on a breathtaking stretch of Cape Peninsula coast, the township of Masiphumelele is home to 23 000 people on about 40 hectares of land.* Despite its name which means ‘we shall succeed’ in isiXhosa, living conditions here are dire. It is overcrowded, sanitation is not what it should be, and infectious diseases like HIV and tuberculosis (TB) are rife.

Professor Robin Wood in the new laboratory. Photo by Joyrene Kramer.

According to University of Cape Town Emeritus Professor Robin Wood, TB infections in the community are astronomically high, particularly amongst children and adolescents.

‘So at the moment, here in Masiphumelele,’ says Wood. ‘Kids of about five years old; 20% of them are infected with TB before they go to school. At the time they’re 14, about 50% are infected, and by the time they leave school, 65 to 70% of them are infected.’

These rates, he says, are applicable to other impoverished communities in the Western Cape, and across South Africa.

The question is ‘why?’

This is what Wood endeavours to learn at a new world class tuberculosis facility officially launched in the heart of Masiphumelele, at the Desmond Tutu HIV Foundation – of which Wood is CEO – on February 20. He says the new Aerobiology TB Research Facility will operationalise leading technology for studying TB transmission, by capturing and analysing exhaled breath from patients recruited at two local clinics: one in Masiphumelele and another in the nearby township of Ocean View.

The patients are brought to the laboratory, where, inside an airtight unit, their breath in captured for an hour. About 500 liters of expired air is collected, and then scanned for TB particles.

‘So what we do,’ says Wood. ‘We identify bugs in the air that people are breathing out. We use new techniques to show that the organisms are TB and that they are alive, without having to culture them (slowly grow them in the lab), which normally takes around six weeks or so. So we’re getting a measure of the infectivity, which I think is key.’

Not nearly enough being done to stop transmission

Photo by Joyrene Kramer

Referring to the fight against TB, Wood argues that prevention is just as important as cure. He says that while treatment of TB patients in South Africa is effective, not nearly enough is being done to stop transmission of the disease.

‘The philosophy behind the new centre,’ says Wood. ‘It is that we have a TB epidemic, which is now worse than anywhere else in the world. I think we need a new approach to this. For example, we know that infection is being acquired by children in schools, but again, we do nothing about it. So my feeling is, I’m trying to get people to refocus. This is an infectious disease. Why don’t we try and address people who are getting it, and try to stop them from getting it? Treatment is good; people used to die on average in two years after getting infected, treatment changed that around dramatically. But it hasn’t decreased the rate at which people are getting infected.’

Over the years, Wood’s research has taken innovative approaches to exploring TB transmission and the socio-environmental factors that drive it.

One such approach is to give people CO2 breath monitors that also tracked their location using GPS. This kind of research helps researchers to understand in which settings the most air is being swapped – with such settings presenting a higher risk of TB transmission if someone in that setting is coughing out or exhaling TB bacteria. One 2017 study co-authored by Wood found that the risk of TB transmission in Masiphumelele was particularly high in schools.

In 2011 he co-authored research published in the South African Medical Journal showing that the risk of becoming infected with TB in Pollsmoor Prison was around a staggering 90% a year. In a landmark judgement in 2012 the Constitutional Court found the state could be held liable for Dudley Lee contracting TB whilst being held in Pollsmoor. Wood wrote an expert affidavit in that case drawing on the 2011 study.

Not enough has materialised

There are around 322 000 TB infections in South Africa per year. South Africa’s National Strategic Plan on HIV, TB and STIs for 2017 – 2022 includes an objective to ‘promote TB infection control’. To this end it specifies: ‘infrastructural changes to improve ventilation; introducing appropriate legislation and building regulations; developing norms and standards for housing and congregate settings including schools and public transport; and developing guidelines for TB infection control in congregate settings and households.’

Yet, a frustrated Wood says not enough of this has materialised. Inside his office, adjacent to the new Aerobiology TB Research Facility, a rubber stress ball sits on his desk.

‘So one of my pet annoyances is that we know where TB spreads, particularly at high rates, for example prisons such as Pollsmoor,’ says Wood. ‘We lock people up for 23 hours a day in rooms with no ventilation and we’re surprised that an airborne disease takes place in such numbers. Why don’t we do something about that? So that’s all we have to do in prisons: we have to change the socio-environmental circumstances they’re in. It’s not rocket science. This is a disease that is spread airborne. So it’s the amount of air that people swap with each other. And that’s determined by indoor environments with crowding and not enough ventilation.’

A mural outside the laboratory. Photo by Joyrene Kramer.

At the Aerobiology TB Research Facility, Wood hopes to soon test adolescents, including pupils from the Masiphumelele High School, which is next door to the premises.

‘One of my arguments is that if we want to control TB, we have to stop infecting children. Where they’re getting infected and how they get infected is something we need to further explore,’ he says.

Also on the Desmond Tutu HIV Foundation’s premises, a youth centre has computers for pupils to work on, while a youth friendly clinic offers free sexual and reproductive health services. The buildings are bright and sunlit, built around a courtyard with trees and flower beds. After school, pupils stream across a dirt road from the school to the centre, where a homework club is hosted daily from 3 to 4:30pm.

‘So we’ve always tried to mix social activity with health,’ says Wood. ‘This new era biology TB unit, it’s just the latest addition to a spectrum of things we do here in Masi.’

*These figures are estimates. When contacted by Spotlight, City of Cape Town spokesperson Simon Maytham said the city’s last official Masiphumelele population figures were from the Stats SA 2011 census. ‘Masi is comprised of an informal settlement component, a temporary relocation area and a number of formal erven with backyard tenants, and we only have some of this info as it stands,’ he said.

 

 

#FootSoldiers: Do the work that nobody wants to do

Dr Marlisa Van Rensburg is known to many in Klerksdorp as the “TB Expert” To date, she has seen over 5 050 patients. Here she is photographed with Sam, one of the children who are being treated at the Tshepong TB unit. Photo by Thom Pierce.

Dr Marlisa Van Rensburg keeps a meticulous register of every tuberculosis (TB) patient she has ever seen. To date, she has seen 5 050 patients at Tshepong Hospital in Klerksdorp in the North West province. She has the names of each and every patient. “It helps me track if patients are coming back,” she says nonchalantly, but from the way she speaks about her work, one can tell these are more than just numbers to her.

At the start of the nineties, very few doctors were willing to take up the fight against TB. Faced with the option of Oncology or TB, Van Rensburg opted for TB. “I believed that there was hope with TB, it’s curable, with cancer it’s not so easy,” said Van Rensburg. But more than just taking the “easier” path, Van Rensburg chose to follow the words of businessman Anton Rupert who she recalls saying the following soon after the end of apartheid: “Things are changing, and you must accept that change. You must find the work that nobody wants to do, and when you find that job, you must do it well.”

It was those words and the need to spread hope that Van Rensburg took to her work in treating TB patients. Later, she carried the same attitude towards drug resistant TB patients.

In 2000 the Department of health opened a TB unit at the Tshepong Hospital.  Since then Van Rensburg has worked alongside her colleague Dr Hannetjie Ferreira. The two doctors and a complement of dedicated nurses and admin staff started to cure patients who arrived at the unit on deaths door. In that first year the clinic saw 56 patients, and now in 2019, the unit sees at least 56 patients in a month. Later, Van Rensburg reveals that her register also contains data on their yearly death and cure rate at the facility. She says that in 2015, the Tshepong  XDR TB unit had the best cure rate in the country at 80%.

Although the TB Unit is attached to Tshepong hospital, it is not part of the main hospital building. At the TB unit patients and the unit staff interact as old friends, little children are playing together, and there are patients seated outside in a garden lapa that is surrounded by white roses. The nurses jokingly refer to the facility as “our holiday resort” .

As we walk through the unit, there are very few patients lying in the wards. Those that are in the wards, are there for a simple lie down, not because they feel ill. There are patients milling about the communal cooking space, walking about the corridors and chatting to each other cheerfully. But perhaps the most striking thing about the “resort” is that in both the MDR and XDR sections of the unit- there isn’t a single healthcare provider who walks around in a TB Mask.

Instead, the unit is kitted out with Ultraviolet germicidal light (UVC lights that kill the TB bacteria within a 3 metre radius. There are no curtains in the facility , as a practical measure to ensure that windows are always open. The patients are highly educated about infection control as well as the importance of taking their treatment. Although the patients are referred to as patients, they are not made to feel as though they are just another number. The hospital staff and the patients are a tight knit group who know each other by name and are always stopping during their rounds to enquire about how the patients are doing, not just medically, but also emotionally and socially.

Other than being a TB expert, Van Rensburg also doubles up as a social worker. Often times her patients come from impoverished backgrounds, facing many social ills. Van Rensburg then takes it upon herself to engage the department of social development to ensure that her patients have access to which ever kind of grant that will assist them the most.

“Many of our patients come from the surrounding areas, and we know how difficult things are there for them, so we try to do more than just assist them medically,” explains Van Rensburg.

One such patient who has required extra social support is a little 14-year-old boy called Sam*. Sam has been at the Tshepong TB unit for the past two years. One afternoon, Sam came home from school feeling unwell, with a constant cough. Eventually his father took him to Tshepong hospital to be seen to, but he never came back for him.

Sam has now been at the facility for the past two years, diagnosed with drug-resistant TB. During his initial admission Sam was diagnosed with TB. When he was discharged into the care of his mother, he stopped taking treatment. By the time he made his way back to the facility he had drug-resistant TB.

“Sam is a troubled boy, he comes from a very bad background, we tried to put him in a foster home, but he would always run away to go back to his mother. We’ve decided to keep him at the facility until the end of his course, but I do not know what we’re going to do with him after that,” says Van Rensburg.

Sam’s tiny frame balances delicately on a hospital bed in the ward, he is very small for his age, his forearms are covered in mosquito bites, and he keeps his forefinger to his lips, moving it only to answer questions very quietly. “My mom has never come to see me, not once. And I really miss her. The nurses look after me here, but I do get bored. All I ever do is lie around, watch TV, sometimes I want to play pool, but nobody really wants to play with me,” he says.

Surprisingly, his face lights up when he starts to speak about politics. He is quite assertive in his beliefs “If I could vote, I would vote for Cyril Ramaphosa, I hate Zuma. Actually, Zuma should have died, not Nelson Mandela,” he says.

Under the care of  Van Rensburg and the staff at the Tshepong TB unit, Sam is expected to make a full recovery.

“The greatest thing is that when these people come, they are at deaths door, but by the time they leave, they are dancing out of here,” said Van Rensburg

But with the 2018 North West strikes and other chronic problems in the public healthcare system the job is not always easy. Last year Van Rensburg did not receive a salary for a period of three months, due to complications with the renewal of her contract. Despite that, she showed up for work every single day. Her reason?

“Some sucker has got to do it”

*Name has been changed to protect the patients identity as he is a minor.

  • Foot soldiers of the health system: It’s election time which means men and women in party regalia take to the streets, podiums, loudhailers and stadiums. Invariably they tell people about all the good and wonderful things they have done or plan to do in the health system. SECTION27’s Nomatter Ndebele and photojournalist Thom Pierce travelled the roads of South Africa in search of the foot soldiers of the health system, the men and women who quietly get on with doing the job and saving lives, often without any acknowledgement.

 

 

New guides to advocating in AIDS councils

Spotlight has developed two new advocacy guides for members of provincial or district AIDS councils. One focuses on TB prevention and the other on retention in care of people living with HIV.

These are practical advocacy guides that we hope will be useful to members of AIDS councils who wish to find district or provincial-level solutions to these two critical problem areas in the HIV and TB response in South Africa.

The guides can be downloaded for free by clicking on the links below. The guides have been designed to be printed on A4 pages that can be folded after printing.

Let’s Make AIDS Councils Work – HIV

Let’s Make AIDS Councils Work – TB

 

Let us know what you think about the guides in the comment section below.

New science: Highlights from CROI2019

Last week the Conference for Retroviruses and Opportunistic Infections (CROI) was held in Seattle, USA. Spotlight did not attend this year’s conference, but fortunately all CROI abstracts and presentations are made available online. Below we have picked some highlights of relevance for South Africa.

1.  New TB prevention therapy works well with dolutegravir

From July the antiretroviral drug dolutegravir will become part of the standard first line treatment for HIV in the public sector in South Africa. Also, in 2019, it is expected that South Africa will introduce a new standard therapy called 3HP for the prevention of TB. The 3HP regimen involves taking a weekly pill containing the medicines isoniazid and rifapentine for three months.

A study presented at CROI found that it is safe to take dolutegravir-based antiretroviral therapy together with 3HP without adjusting the dosage of either. This is good news for patients, since it means that they will not have to take extra dolutegravir pills as was feared might be the case. The confirmation of safety also means that 3HP is now likely to be included in TB prevention guidelines in South Africa and made available in the public sector – providing a low enough price can be negotiated. You can read HIV I-base’s coverage of the study here.

2 .  Using two important new tuberculosis treatments together is safe

Bedaquiline and delamanid are the only new TB medicines to be approved in decades – both for the treatment of drug-resistant forms of TB. Drug-resistant forms of TB are treated with anything from three to eight different medicines – typically around five. Yet, until now it was not known whether it is safe to use these two new drugs together – both impact heart rhythms (so-called QT intervals).

A study presented at CROI found that it is indeed safe to use these two drugs together, providing a baseline heart test is done when treatment is started to rule out pre-existing heart risk. The researchers concluded: “The combined effect on the QTcF interval of co-administration of bedaquiline and delamanid is clinically modest and no more than additive. You can read the full abstract here.

This study will likely contribute to updates in both WHO and South African treatment guidelines for drug-resistant TB.

3.  Monthly ARV injections appear to be safe and effective

Two studies presented at CROI explored the use of monthly injections of the two ARVs cabotegravir and rilpivirine for HIV treatment – the one study in people already stable on HIV treatment and the other in patients newly starting treatment. Both studies found the injections to be about as safe and effective as daily pills. For more detail, see HIV I-Base’s write-up of the two studies here.

It now seems likely that, for at least some people, monthly injections will become an alternative treatment option to daily pills in the next few years. The usual issues with price, registration and public sector availability still lie in wait. In addition, whether people will prefer monthly injections to daily pills out in the real world remains to be seen – in these two studies at least patients were very positive about the injections.

4.  New HIV prevention therapy seems as good as current standard

The current gold-standard in HIV prevention treatment is the combination of the medicines tenofovir and FTC in pill form. TAF is a new form of tenofovir that allows for smaller pills and appears to have a slightly better safety profile. A study presented at CROI found that TAF plus FTC was as effective as traditional tenofovir plus FTC in preventing HIV infection while appearing to be better for bone density and the health of the kidneys. The study was conducted in gay men and transgender women, but the findings are likely generalisable to other groups. TAF has been licensed to the Medicines Patent Pool, so affordable generics of this new option for HIV prevention are likely not too far away.

5.  Integrase inhibitors seem to cause moderate weight gain

Integrase inhibitors, the class of drugs including dolutegravir, appears to be associated with a slight  increase risk of weight gain. There are a number of studies looking at this issue and the findings are not conclusive as to what sub-group of people are most at risk and which integrase inhibitors are most strongly linked, but the general finding of an increased risk seems to be well-founded. As pointed out in a summary of the evidence on the website AIDSMap, the weight gain is fortunately not like that associated with lipodystrophy (a side effect of earlier ARVs such as d4T that lead to abnormal fat distribution that many found stigmatising). Either way, the potential for modest weight gain may or may not turn out to be an issue as dolutegravir becomes available in the public sector in South Africa.

6.  Massive HIV prevention study confirms importance of community healthcare workers

PopART is possibly the largest HIV prevention study ever conducted. The key PopART intervention included annual home-based HIV testing provided by community healthcare workers who also supported linkage to care, treatment adherence and other related services. The study randomised 21 communities in South Africa and Zambia to one of three interventions: universal treatment plus the PopART intervention, treatment according to local guidelines plus PopART, and a control arm with the standard of care in the country without PopART.

The universal coverage plus PopART arm had a 7% lower incidence rate than the control arm – a finding which was not statistically significant. The local guidelines plus PopART arm however had a statistically significant 30% lower incidence than the control arm. The counter-intuitive finding that incidence was higher in the universal treatment group than the local guidelines group is puzzling. Even so, the underlying indication that community healthcare workers working in the PopART model can help bring down incidence is compelling. AIDSMap reports that it emerged in questions after the session where the findings were presented that the two PopART arms together had 20% lower HIV incidence than the control. To what extent government will implement aggressive PopART-style interventions of course remains an open question.

The researchers concluded their abstract: “Community-based HIV testing and linkage is a key component of combination prevention in efforts to achieve effective HIV control.” You can read the abstract here.

7. Food vouchers increases HIV testing in men in KwaZulu-Natal

Getting more men to test for HIV is one of the biggest challenges in South Africa’s HIV response. A study conducted in KwaZulu-Natal tried three different interventions to encourage men to take up home-based HIV testing in different communities – comparing all three interventions to the current standard of care. In one set of communities men were offered R50 food vouchers as an incentive to test, in another the vouchers were offered together with male-targeted counselling provided through an App, and in the third the counselling was offered without the voucher. While the counselling App did not have much impact, the probability that men would test was increased by about 50% in the communities where vouchers were offered. The researchers concluded that: “Micro-incentives significantly increased the uptake of home-based HIV testing among men in rural South Africa and should thus be considered as a policy option where HIV testing rates are low.” You can read the full abstract here.

8. Second man cured of HIV

Much of the headlines from this year’s CROI were dominated by reports of a second man ‘cured’ of HIV following a stem cell transplant. While these cures are important scientific advances, they are of no immediate relevance to almost all people living with HIV given that it involves an extremely dangerous procedure that one would only risk when faced with the serious risk of death. HIV I-Base has written a good summary of the case here and long-time AIDS activist Gregg Gonsalves did a good job of putting it all in perspective here.

 

Is South Africa on track to meet NSP targets?

On World AIDS Day 2018 we assess how South Africa is faring against 10 key targets set in the National Strategic Plan (NSP) on HIV, TB and STIs 2017 – 2022. The current picture is mixed, with areas of impressive progress, such as HIV testing,  offset by some serious red flags, such as retention in care.

Of the 10 targets, we have assessed two as “Appears target will be reached”, two as “Target is within reach”, four as “Reaching the target will be difficult”, and two as “no sufficiently reliable figures”.

In future articles we will assess progress against other important issues in the NSP not covered here such as stigma, availability of data, and accountability in the public healthcare system. Accountability for the development of implementation plans and actual implementation is an ongoing problem with the NSP – although there are now signs that it may be addressed. The South African National AIDS Council (SANAC) reports that it is currently “developing an NSP Accountability framework and scorecard for accountability to achieve the goals of the NSP 2017-2022 for HIV, TB and STIs”.

“The accountability framework will assist in ensuring commitment to set priorities by individual role players in the current and subsequent NSPs,” SANAC explained in response to questions from Spotlight. “The Framework will nationally determine who should be accountable, for what, why and how. The development of the accountability framework will require extensive consultations to ensure ownership in the national response.”

SANAC also indicated that its mid-term review of the NSP will be published by August 2019. The mid-term review is expected to include up-to-date estimates for all the indicators covered in this article.

1.Reduce new HIV infections to less than 100 000 by 2022 (or 88 000 by 2020)

According to the Thembisa model (a sophisticated mathematical model of HIV in South Africa) there were around 275 000 new HIV infections in South Africa in 2017. This number is higher than the 231 000 estimated in the South African National HIV Prevalence, Incidence, Behaviour and Communication Survey 2017 (the HSRC survey).

Either way, given the current trajectory it seems highly unlikely that South Africa will get new infections down to below 100 000 by 2022. The Thembisa model projects that new infections will only drop to around 198 000  by 2022 (with the low end of the 95% confidence interval around this estimate at 184 000).

According to SANAC, the target for New infections has now changed to 88 000 by 2020, an even more ambitious, and arguably more unreachable, target.  “The change/adjustment has been made in line with  the global UN Prevention road map to accelerate HIV prevention strategies and reach national and global goals to end the threat of AIDS by 2030,” SANAC explained in a response to Spotlight. “The NSP Steering Committee agreed that the change in the targets according to the Prevention Revolution will be incorporated into the NSP M&E Plan (rather than in the NSP programme narrative).  The NSP M&E Plan will be available once approved by all SANAC structures.”

Verdict: Reaching the target will be difficult

2. Reduce annual new HIV infections in women and girls aged 15 to 24 to 30 000 by 2022

The targets section of the NSP lists the 30 000 target, while earlier in the NSP reference is made to bringing the infection rate in young women and girls down to less than 800 new infections per week (which works out to around 41 000 per year). Either way, it is widely agreed that reducing new infections in young women and girls is of critical importance.

According to the Thembisa model there was around 81 000 new infections in women and girls aged 15 to 24 in 2017 (this works out to just over 1 500 per week, rather than the more widely quoted 2 000 per week.). Thembisa projects annual infections in this group only dropping to around 58 000 by 2022 – almost double the target.

Verdict: Reaching the target will be difficult

3. The rate of mother-to-child transmission of HIV at 18 months must be below 2% by 2022

According to the Thembisa model the mother-to-child transmission (MTCT) rate was 4.81% in 2017. The model projects this dropping to around 3.5% by 2022. This number however includes transmission that occurs after 18 months, and the 18 month number might thus be very slightly lower. While there are other sources for MTCT rates, we prefer quoting the Thembisa estimates since the model factors in MTCT cases where the mother is not aware of her status – likely the majority of MTCT cases.

For the MTCT rate to come down further will require that a higher percentage of HIV-positive women of child-bearing age take antiretroviral therapy and achieve viral suppression. It will also require that we help more breastfeeding women who are not living with HIV to stay HIV negative – since women who become HIV-positive in the months they are breastfeeding account for a large proportion of onward transmission to children.

Verdict: Reaching the target will be difficult

Implement the 90-90-90 strategy for HIV

The 90-90-90 targets first proposed by UNAIDS were adopted in South Africa’s current NSP. There was previously some uncertainty regarding whether the three targets (described below) are to be met by 2020 (as per UNAIDS) or by 2022 (the end date of the NSP). Our understanding is that the agreed target date for South Africa is 2020.

4. 90% of all people living with HIV know their HIV status

The Thembisa model estimates that South Africa has already reached the first 90, with an estimated 90% of people living with HIV knowing their status in 2017. By contrast, the HSRC survey suggests that South Africa is just below the target, with around 85% of people aged 15-64 in South Africa who are living with HIV knowing their HIV status.

While South Africa appears to have done well on the first 90, maintaining a high score on the first 90 will require sustained testing efforts given that over 200 000 people are newly infected every year (and obviously do not know their status until testing). Thembisa projects that South Africa will reach around 92.4% by 2020.

Verdict: Appears target will be reached

5. 90% of all people with diagnosed HIV infection receive sustained antiretroviral therapy

According to the Thembisa model, South Africa is doing much poorer on the second 90, with only around 61.9% of people diagnosed with HIV receiving antiretroviral therapy in 2017. The HSRC survey paints a slightly rosier picture, estimating that around 71% of people aged 15-64 with diagnosed HIV infection are receiving sustained antiretroviral therapy. According to the Thembisa model projections South Africa will reach only around 70.4% by 2020.

South Africa’s poor performance on the second 90 is arguably the biggest red flag in the set of indicators examined in this article.

Verdict: Reaching the target will be difficult

6. 90% of all people receiving antiretroviral therapy are virally suppressed

In terms of the third 90, the Thembisa model estimates that around 77.8% of HIV positive people who were receiving treatment in 2017 were virally suppressed (the virus was so successfully suppressed in their bodies that it could not be detected with standard tests). Again the HSRC survey paints a more positive picture than Thembisa, estimating that 86% of people aged 15-64 receiving antiretroviral therapy have viral suppression.

Even though these figures are relatively high and may well go up with the introduction of dolutegravir-based antiretroviral therapy in South Africa, it is by no means certain that it will rise to 90 in the coming years and then be maintained above 90 (Thembisa projects around 86% by 2020).

Verdict: Target is within reach

A related indicator that does not directly form one of the three 90s, is the percentage of all people living with HIV who are virally suppressed (not just those on treatment as per the third 90). The Thembisa model estimates that 43.3% of all people living with HIV in South Africa were virally suppressed in 2017 (the implicit target based on the 90-90-90 target is 73%). Compelling scientific evidence shows that people who are virally suppressed do not transmit HIV.

Implement the 90-90-90 strategy for TB

As with HIV, TB also has a set of 90-90-90 targets that have been integrated into the NSP. Given that TB figures are harder to find than HIV figures, Spotlight twice wrote to the Department of Health to request the most recent estimates they have for these indicators. While the department did acknowledge our request, we did not receive any figures by the time of publishing. SANAC also failed to provide Spotlight with estimates regarding the 90-90-90 targets for TB.

Below we use the targets as they are presented in the final NSP. It is notable however that the 90-90-90 targets for TB has been taken to mean different things in different contexts. A recent Health Systems Trust publication describes the targets as “90% of people with TB will be screened, 90% will be initiated on  treatment, and 90% will successfully complete treatment” – which is not the same as the targets from the NSP used below. Where we found targets unclear we have attempted to clarify them with reference to the WHO’s version of the 90-90-90 targets for TB.

7. Find 90% of all TB cases and place them on appropriate treatment

The WHO’s version of this target is formulated as follows: “Reach at least 90% of all people with TB and place   all of them on appropriate therapy: first-line, second-line and preventive therapy, as required.”

In our understanding the indicator that most closely tracks whether we are finding people with TB is the case detection rate. According to figures available from the WHO’s TB data portal South Africa’s case detection rate was 68% in 2017. But the WHO also has the case detection rate at 68% for each of the last six years – something which does not inspire much confidence in this number. Neither the Department of Health or SANAC provided figures for this indicator despite various requests from Spotlight.

Recent testing campaigns in mining and other high-burden areas have been an important step in the right direction. Indications are that we are most likely still failing to diagnose many thousands of TB cases – one recent study found that most people with active TB who attend clinics in the Eastern Cape were not properly screened and tested. In addition to improving the quality of screening that should be happening at primary healthcare facilities, rapid and widespread implementation of the increased contact tracing and active-case-finding efforts described in the NSP will be critical if this target is to be met.

Verdict: No sufficiently reliable figures

8. Treat at least 90% of those diagnosed with DS TB and 75% of those with DR TB.

We understand “treat” here to refer to successful treatment as per the WHO version of this target. The WHO states it as follows: “Achieve at least 90% treatment success for all   people diagnosed with TB through affordable   treatment services, adherence to complete and   correct treatment, and social support.”

According to WHO figures around 82% of people with drug-sensitive TB and 55% of people with drug-resistant (MDR or Rifampicin Resistant) TB in South Africa were successfully treated in 2017. Neither the Department of Health or SANAC provided figures for this indicator despite various requests from Spotlight.

While reaching the 90% treatment success target for DS TB is within reach, reaching the target cannot be taken for granted given the many challenges facing the public healthcare system in South Africa. The introduction of better and less toxic treatments for drug-resistant forms of TB should help push the DR TB treatment success numbers up in the coming years.

Verdict: Target is within reach

9. Find at least 90% of the TB cases in key populations (the most vulnerable including people living with HIV with low CD4 counts, under-served, at-risk) and place them on appropriate treatment. Successfully

We have not been able to find reliable figures for this indicator. Neither the Department of Health or SANAC provided figures for this indicator despite various requests from Spotlight.

Verdict: No sufficiently reliable figures

10. Reduce TB incidence by at least 30%, from 834/100,000 population in 2015 to less than 584/100,000 by 2022

According to the 2018 World Health Organization (WHO) World TB Report, TB incidence in South Africa was 567 per 100 000 in 2017. At first glance it thus seems that we have already achieved the NSP target of less than 584 per 100 000. The reality is however more complicated. In 2018 the WHO made major adjustments to its TB estimates for South Africa. This included recalculating the estimate for 2015 as 759 per 100 000. A 30% reduction of this figure would set a target for 2022 of 531 per 100 000. The estimate of 567 per 100 000 is still above this level, but by 2022 South Africa will be well below this adjusted target if the downward trend suggested by the WHO’s figures  continues.

That said, there is significant uncertainty regarding TB incidence in South Africa and the picture might well change substantially as new information becomes available in the coming years. While the 567 per 100 000 figure may be the figure most often quoted, the WHO estimates that the real figure could be anywhere between 406 and 754 per 100 000.

Verdict: Appears target will be reached

Conclusion

  • Regarding HIV, the good news is that South Africa is doing well when it comes to HIV testing and where people living with HIV are on treatment the treatment is generally working and saving lives.
  • The bad news is that many people who are living with HIV are not on treatment – either never having started or having quit. Arguably the biggest challenge facing the public healthcare system today is to support many more people living with HIV to start and stay on treatment. Doing this in an often dysfunctional healthcare system will not be easy.
  • Regarding TB, the good news this year is that South Africa’s TB epidemic appears not to be quite as large as previously thought. TB rates appear to be coming down slowly, although it is hard to say with any certainty exactly how fast – chances are not fast enough.
  • The bad news is that even in 2018 many people in South Africa with TB do not get diagnosed. Again the available figures cannot be trusted, but even if the real figure is only half of the estimated 90 000 to 100 000, we are still facing a very serious situation.
  • Either way, it is clear that in addition to gathering better data on TB, as is being done with South Africa’s first TB prevalence survey, South Africa also needs better epidemiological models of TB along the lines of what we have for HIV.