In-depth: The problem of stopping or not starting HIV treatment
By Thania Gopal
South Africa has the largest HIV epidemic in the world. The United Nations Programme on HIV/AIDS (UNAIDS) estimates that there are approximately 7.2-million South Africans living with HIV, with 270 000 new HIV infections in 2017. South Africa also has the largest antiretroviral therapy (ART) programme with more than four million people estimated to be on treatment. Despite progress in getting people onto treatment, recent evidence indicates that the country is still experiencing significant numbers of people developing and dying from advanced HIV-disease. This is as result of people who either do not start treatment, start treatment late, or stop and re-start treatment. There is, therefore, an urgent need to not only prioritise HIV-testing but to ensure that once people start treatment, they remain on life-long care.
As part of its National Strategic Plan for HIV, Tuberculosis and STIs 2017 – 2022, South Africa has adopted the UNAIDS 90:90:90 targets which aims to achieve the following HIV-related goals by 2020: (1) 90% of all people living with HIV should know their HIV status (2) 90% of all people with diagnosed HIV infection should receive sustained antiretroviral therapy, and (3) 90% of all people receiving ART should be virally suppressed.
Deputy Director-General of Health, Dr Yogan Pillay, says that while South Africa is not doing too badly with regards to testing people for HIV and keeping them virally suppressed while on ART (the first and third targets), the main challenge is keeping people on treatment.
Estimates from Thembisa (the leading mathematical model of HIV in South Africa) indicates that South Africa has already achieved and surpassed the first 90, with an estimated 90% of people living with HIV knowing their status in 2017. Although South Africa appears to be performing well in terms of HIV-testing, this progress will need to be sustained given the large amount of new infections annually.
In addition, the testing of specifically men and young people remains a problem. According to Professor Francois Venter, Deputy Executive Director at the Wits Reproductive Health and HIV Institute, the 90:90:90 targets for men are an “absolute disaster” compared to women. “Men test late, they don’t link to care, they are less likely to suppress, they are more likely to fall out of care, they are also more likely to come to treatment much later. So, it’s a really big challenge at the moment”, he says. Similarly, Pillay says that even when men are tested and test positive, there is a reluctance to initiate treatment.
Dr Laura Trivino-Duran, Medical Coordinator for Médecins Sans Frontières in South Africa cautions against thinking about 90:90:90 targets as a linear model in which people who “start on treatment will stay on treatment forever” and says the cyclical nature of the treatment journey in which people start care, exit care and restart care – for a number of different reasons – should be recognised.
Poor performance on second 90
With regards to the second UNAIDS target of having 90% of HIV-diagnosed individuals on ART, based on the Thembisa model, South Africa only had around six out of every 10 (61.9%) of HIV-diagnosed people receiving ART in 2017, with the provincial rate varying between about half (54%) in Gauteng and North West, about six out of every 10 (64%) in Western Cape and eight out of every 10 (81%) in the Northern Cape.
The model estimates less than half (40%) of people with HIV were still not on treatment in 2017, this is roughly three million people at risk of progressing to advanced HIV-disease.
For the third 90, the model estimates that almost eight out of every 10 (77.8%) HIV-positive people who were receiving treatment in 2017 were virally suppressed, meaning the virus could not be detected in their bodies. According to the model, well below half (43.3%) of all people living with HIV in South Africa were virally suppressed. This is important because people who are virally suppressed do not transmit the virus.
Dr Leigh Johnson, from the Centre for Infectious Disease Epidemiology and Research at the University of Cape Town and lead developer of the Thembisa model, says there has been “a slower than expected growth in the ART programme” with the number of patients initiating ART peaking at around 720 000 in 2010 and steadily declining to approximately 479 000 per annum in 2016.
The big controversy
“I think the big controversy is really around where are we failing, are we failing to diagnose people, are we failing to link people to care after that initial diagnosis or is the problem that we actually just aren’t retaining people in care?”, says Johnson.
Pillay says there are two challenges: “The one is that patients are still shopping around even after being diagnosed positive with the rapid test and there’s also a delay to treatment. The other reason for delay to treatment is that patients are not always offered same day initiation and when they don’t initiate on the same day, we find it very difficult to get them back into care”.
In 2016, following results from the landmark START trial, government expanded eligibility criteria for ART by introducing a “Test-and-Treat” policy which called for all people diagnosed with HIV to be initiated onto treatment as soon as possible, irrespective of their CD4 count. According to Venter, the policy has been surprisingly effective: “I used to be a bit sceptical about it, just thinking that people need time to get ready, but in fact, for many people, just taking that first step immediately, and not having to sit around thinking about it is probably quite a healthy thing”, he says.
There are many factors which contribute to patients not starting ART, says Professor Catherine Orrell, from the Desmond Tutu HIV Foundation. “It’s often personal reasons, there’s a lot of stigma, there’s a lot of non-disclosure because people are afraid of what their family and friends will say about their HIV status”. She adds that South Africa is still “suffering from the side-effects” of AIDS-denialism, during which certain groups denied that HIV even existed. South Africa is still a conservative society, despite living in a country where one in eight people have HIV, there are very few public figures such as sports stars, radio celebrities or politicians that have openly disclosed their status, says Venter.
High drop-out rate
Another major issue is keeping people on treatment with suppressed viral loads once they have started treatment. At the Gugulethu Clinic, in Cape Town, where Orrell works, around one in five (20%) of people who have started treatment at the clinic have left care by week 16.
“Within four months, 20% of people have left care, of those that come to start care, so there’s definitely a retention issue as well. There’s a very steep drop off in numbers in that first four months and then there’s an ongoing slow trickle of drop off,” she says. Similar results were seen in a larger study1 in Khayelitsha using clinic data of 39 884 patients who had visited one of 13 Khayelitsha ART clinics during 2013/2014. The study found that just over one in five (22.6%) of patients disengaged from care at least once during 2013/2014 and an additional number (2.5%) transferred to a different clinic from the one in which they had originally started on ART. While a third of patients in the study returned to care after stopping, an additional quarter were alive but not in care.
Pillay said around 20% of patients default at six months after starting ART and up to 30% of patients default at twelve months after initiating treatment.
Trivino-Duran says that in the past, advanced HIV-disease was predominantly seen in people who had not started on ART and who became ill. Currently, the majority of people with advanced disease have been on ART before and have stopped or interrupted treatment.
Two recent studies highlight a worrying trend of people who already have advanced HIV-disease, starting treatment late. One study2 (based on countrywide laboratory data) found that of 654 868 patients starting care in 2016, almost one third (32.9%) had advanced HIV-disease. Another study3, using Western Cape provincial data of all HIV patients receiving CD4 count testing, found that an increasing proportion of patients with very advanced HIV-disease had previously been on ART. Between 2006 and 2016, patients with advanced HIV-disease getting treatment for the first time dropped from 60.9% to 26.7% whereas the proportion who had previously been on ART increased from 14.3% to 56.7%. This points to a major problem of patients not remaining on continuous care.
Trivino-Duran is also concerned about a potential blind spot in missing patients who are discharged after being treated for advanced HIV-disease and who may be lost to follow-up again. “What happens when they are discharged from hospital, and they have to go back to the health facility, that’s a very crucial period of time where I think we need to strengthen our follow-up of those patients – once they are discharged and not completely well, they are still a bit fragile.”
According to Professor Graeme Meintjes, from the Institute for Infectious Disease and Molecular Medicine, based at the University of Cape Town, the costs of treating patients who require hospital admission for advanced disease is enormous compared to people who are stable and doing well on ART as an outpatient. Ideally, the ART programme should work in such a way that it is keeping people healthy and preventing people from developing advanced HIV, says Meintjes.
No effective tracking system
A major obstacle to keeping people on treatment in South Africa is the high rates of mobility of the population with no consistently reliable method of tracking patients across different health facilities.
“Each province has different systems, and different ways of doing things, and to have a unique tracking system across the country would be immensely valuable”, says Orrell. The absence of a reliable tracking system makes it difficult to know if patients are receiving treatment at a different facility or if they have truly stopped treatment altogether.
According to Venter, “If you don’t have a single patient identifier you don’t know what you are fixing, you don’t have proper data. It would help governance and programmes immeasurably being able to track how people are using services and who is and who isn’t included… and it will make things smarter, cheaper, more effective, and it allows us to understand how our health care service needs to operate”.
However, Pillay says the problem of a unique identifier has been resolved both “conceptually and practically”. He says there are currently around 26-million South Africans who are linked to the Health Patient Registration System (HPRS) via a Health Patient Registration Number (HPRN). Instead, the main challenge is internet connectivity at health facility-level and linking the different systems that manage patient-linked data.
Patients also experience difficulty transferring from one clinic to another due to the way that the public health system is structured, says Orrell. She says that patients who do attempt to return to care may be given a hard time by clinic staff if they do not have the proper documentation. “…you have to come get an appointment, you have to get a long letter, you have to go to the other clinic and present the letter, and if you don’t get the letter then it’s hard to get into the next clinic, but people do cycle all the time,” says Orrell.
Healthcare worker attitudes
There are many reasons why individual patients stop treatment including psychological issues, life events, disruptions to their daily schedules, job instability or psychological distress, according to Meintjes.
Another barrier for patients who want to return to care is the attitude of healthcare workers, with patients often complaining about being “shouted at”, according to Trivino-Duran. “I think staff attitude and even the way we talk about the patients, we call them ‘defaulters’, we call them ‘treatment failures’, and those are very punitive words that we use to describe patients”.
Patients who have been on treatment may also suffer from treatment fatigue. “I think the kind of unforgiving attitude of health care workers is very damaging, its completely normal and human to stop, to get tired of therapy, to have life issues, especially for young people, and one can understand that”.
We should be designing a healthcare system where patients can easily access care outside of traditional health facilities, says Venter. “If you educate patients, and you give them power, make them knowledgeable about their condition, they are very, very good at managing themselves”. The Central Chronic Medicines Dispensing and Distribution (CCMDD) programme, for example, enables more than two million patients in South Africa to receive their ART medication at various pick-up points, such as churches and libraries, closer to their homes. “It’s just much closer and the queues are much shorter, so I think that has been really exciting, that we are starting to look at different models of medication delivery that doesn’t mean you have to spend hours waiting,” says Venter.
The NDoH is also trialling a bicycle system to courier medication over the ‘last mile’ from designated pick-up points directly to patient’s homes. This is currently being piloted in two townships in KwaZulu-Natal (KZN) and Johannesburg and is modelled on an initiative in Khayelitsha. “While it is in early discussion, we think it’s something that will also make life easier for patients and therefore increase adherence. Also, because of the distribution of patients, the cyclists who courier the drugs to them can also alert them to when their next appointments are in case they forget” says Pillay.
The role of adherence clubs
An ongoing strategy, forming part of the NDoH’s adherence policy to keep patients motivated and on treatment, is the use of adherence clubs, which brings together groups of patients at a health facility or other community venue to facilitate quick pick-up of pre-packaged ART and to receive counselling and support, usually facilitated by community health workers or lay health workers.
“The clubs cater for the majority of people that are stable on treatment and that have a suppressed viral load. They provide peer support, and they produce that social fabric that is very good for many patients”, says Trivino-Duran.
While adherence clubs have been successful, they also face a number of problems given the rapidly expanding number of people on ART. One problem is that adherence clubs are only allowed to supply medication for two months which is regarded as insufficient and should be extended to up to six months, says Trivino-Duran. Patients who do not require regular peer support, especially those who have been on treatment for a long period, also prefer having a “fast lane” to collect their medication, rather than having to sit through counselling each time.
Another issue in Khayelitsha – where around half (50%) of the HIV-cohort are using adherence clubs – is that the size of the clubs have grown so much that finding an appropriate space to accommodate them is becoming a big problem. In addition, patients with other chronic diseases, are still required to visit health facilities to collect their other medication so “it’s not a single stop service for them,” says Professor Orrell.
“Basically, the message is that we need to have a variety, a number of models of care that caters to everybody and doing only clubs is not the way forward. Clubs are good for a certain population but not for everybody,” says Dr Trivino-Duran.
With regards to adherence clubs, Dr Pillay says the NDoH’s plan is to move toward “peer-led clubs rather than clubs led by community health workers”. He says government has partnered with three organisations managed by people living with HIV and will be working with them to look at how they can support the programme with respect to adherence and treatment literacy.
The role of Community healthcare workers
There is also a lack of clarity with regards to the role of community health workers (CHWs) under the new Policy Framework and Strategy for Ward Based Primary Healthcare Outreach Teams 2018/2019 – 2023/2024, released last year. CHWs are involved in all aspects of HIV-management including prevention, testing, treatment, linkage to care and retention in care.
According to Donela Besada, Senior Research Scientist at the South African Medical Research Council, there appears to be a consolidation of the roles of community health workers, lay health workers and caregivers and an increase in the scope of work which includes HIV/AIDS, tuberculosis, child and maternal health, and non-communicable diseases. “What we had before is a lay health worker that worked in the facility and then we had another community health worker that was out in the community and now what we are trying to find out is what’s going to happen when they put it all under one overall umbrella”.
Another concern is the introduction of a Grade 12 qualification for CHWs under the new policy and what will happen to CHWs who have been working in the system for years.
Going forward, Dr Pillay says CHWs will focus on encouraging people to test and on tracking and tracing patients lost to follow-up.
Treatment closer to home
Many programmes aimed at improving linkage to care and retention in care centre around community-based interventions which bring treatment and support closer to people’s homes.
So, for example, MSF has piloted ‘Welcoming Services’ which is based on making people feel more welcome when returning to treatment after stopping ART. According to Trivino-Duran, this involves utilising a more effective triage system to identify people who may be returning to care outside of their allocated appointments and trying to prioritise or fast-track them, enhancing systems at the health facility, and improving staff attitudes toward patients who are returning to care.
Given that around 20% of patients have defaulted six months after starting ART, Pillay says patients should be followed up immediately after missed appointments via SMS or telephonically. However, he admits that this is often ineffective because patients may change their contact details, provide incorrect details or not respond. When this happens, ward-based outreach teams (made up of CHWs) are given lists of patients to trace their physical locations, which is also challenging.
Trivino-Duran says another pilot, which involves the use of social media platforms such as Facebook, may provide an alternative in areas where smart phone penetration is high. This is being used to encourage people to return to health services without fear of being “blamed” if they have disengaged from treatment for a long time and also to provide them with more information on where to go and what to do.
The NDoH, in partnership with MSF is also piloting interventions aimed at encouraging men to use health services in KZN (Pinetown, KwaMashu) and Cape Town (Khayelitsha). These include providing a package of services customised towards men’s health issues (such as STI screening and erectile dysfunction) rather than offering stand-alone HIV-services, providing a male nurse and fast-track queues for men on Saturdays.
No magic bullet
The use of HIV self-screening tests (using an oral self-testing kit) has also been trialled, particularly among men and sex workers. Current pilots conducted by MSF in Eshowe in KZN and in Khayelitsha in Cape Town have shown promising results. Trivino-Duran said these tests should be distributed on a massive scale, along with further access to information on how to understand the results and access further care. A mobile application is also available which guides people through the self-testing process, and directs them to the nearest facility.
One of the disadvantages of self-testing is that it does not automatically link people to care after testing positive. “What we do know for sure is that people use it, it is accepted, and it doesn’t seem to produce errors and it is easy to do but what we cannot really say, is what people do after getting the results” says Trivino-Duran. An interesting finding from the study was that many patients who used the test already knew their status and used self-testing to “confirm” the results. Therefore, an important learning from the study was to make patients who were already on ART aware that self-testing results would not be the final word, since it could provide false negative results for patients who were taking ART.
A range of different interventions focussed on young people are also being implemented by the DTHF in Cape Town in partnership with the Western Cape government and funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria. Some of these interventions, such as Zimele, provide healthcare services as well as strong educational support and social empowerment, according to Orrell. The Women of Worth (WOW) project is a research study described as a “social protection intervention that will address a range of biomedical, socio-behavioural, structural and economic vulnerabilities” in 10 000 young women between the ages of 19-24 years using twelve “empowerment workshops”.
In addition to the way that the health system is structured and services are delivered, there are also changes to the actual treatment guidelines that should help keep more people healthy. An example, from Meintjes, is the introduction of a new treatment regimen which will be introduced in South Africa later this year, which involves moving patients from Efavirenz to Dolutegravir, as part of a triple therapy regimen. This change in treatment has been shown to result in patients developing less resistance even if they stop and re-start the treatment, “so having a drug that is very resilient in terms of resistance will also help to prevent advanced HIV,” he says.
Ultimately, there is no magic bullet and it boils down to getting the basics right, says Venter. This includes “ensuring that people can walk into a clinic and get decent care, that there are no drug stocks-outs, that the staff know what they are doing, that facilities are clean and safe” and that patients’ needs are being prioritised by being able to access care in the evenings and over weekends.
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2 Carmona S, Bor J, Nattey C, et al. Persistent high burden of advanced human immunodeficiency virus (HIV) disease among patients seeking care in South Africa’s national HIV program: data from a nationwide laboratory cohort. Clin Infect Dis 2018; 66:S111–7.
3 Osler M, Hilderbrand K, Goemaere E, et al. The continuing burden of advanced HIV disease over 10 years of increasing antiretroviral therapy coverage in South Africa. Clin Infect Dis 2018; 66:S118–25.