Interview with Dr. Theresa Rossouw on the problem of HIV drugs resistance in South Africa

‘My guess is that already around 5-10 percent of newly reporting HIV patients are resistant to the drugs and this percentage is increasing’, says Dr. Theresa Rossouw. ‘Unfortunately in the clinic we are unable to perform a HIV drug resistance test on every patient who comes in. This is far too expensive. Therefore, I cannot show results to underpin my guess, but I’m confronted with new cases of patients not reacting to standard HIV drugs every day.’

Maybe Dr. Rossouw does not have the technical evidence yet, but the clinic she works for will sooner or later become a prime outpost in the battle against HIV drug resistance. The Tshawane District Hospital is a busy old public clinic, an hour drive from Johannesburg. It is the first place people report for treatment and the first place where new resistant strains in the community could be identified. Since the clinic started treating HIV patients in 2004 it has seen over 10,000 HIV infected patients come in, adults and children. ‘The workload is enormous. It is a constant battle for the management to get and retain medical staff. Our number of burn-outs is huge.’ Rossouw is one of the six doctors in the clinic and at the same time she is a teacher and researcher at the University of Pretoria.

Despite her very busy schedule, Dr Rossouw finds time to talk with us and give her expert opinion on the problem of HIV drug resistance in South Africa and the importance of programs like PASER  and ART-A  that address this issue. Unfortunately, HIV drug resistance is the inevitable side-effect of the recent success to make antiretroviral therapy accessible in sub-Saharan Africa. Due to an enormous international effort over 4 million people in the world, of whom more than 3 million in Africa, now have access to medication. Although the battle for universal treatment is far from won (still two thirds of Africa’s HIV patients have no access to drugs yet), another enemy is looming for the “lucky ones”: resistance to their once lifesaving drugs.

‘Looming is not the right definition anymore, it is already there. Patients who fail basic 1st  line therapy come in daily. And an increasing number fails 2nd line as well. There is no 3rd line medication available in the public sector. These patients have basically exhausted all options.’

Dr. Rossouw has to face this harsh reality every day. ‘One patient is this wonderful little 8 year old boy Bongi. He lives with his illiterate grandmother. We tried a 1st  line syrup therapy and a capsule mix with water; in both cases the grandma was unable to see and read what the right dose was. He failed 1st line. Now the kid is responsible for taking the 2nd line medication himself. Only eight and the stuff tastes horrible. Unfortunately the effect of 2nd line is compromised as well; I’m so scared for this boy.’

Fighting the problem

Dr. Rossouw is clear that action is needed to effectively fight the problem of HIV drug resistance in Africa. The possible 10 percent of HIV drug resistance case in her clinic is remarkably in line with actual scientific findings within the PASER program. PASER baseline studies in 13 clinics in 6 African countries indicate an overall prevalence of ~7% of drug resistance in naïve patients. In patients with a reported history of previous antiretroviral drug use, PASER reports resistance figures of ~25% .



Understanding at what speed this new enemy is encountering us is according to Dr. Rossouw precisely the reason why PASER and ART-A programs play a crucial role. ‘In South Africa we can at least do viral load testing to see whether a patient is failing. Unfortunately a resistance test does not fit the budget. In most African countries they don’t even have access to viral load. Patients are kept on 1st line although there are already failing for a long time, with the result that they either switch too late and have become resistant to 2nd line. Alternatively, when viral load is not know, the doctor remains in the blind and might decide to switch to 2nd line too soon, thus wasting the effectiveness of 1st line. I therefore think programs like PASER and ART-A are vital. We need to monitor the virus to know what is happening in the community. PASER and ART-A can help to anticipate, to get ahead of the virus.’

While PASER is a prospective monitoring study of patients on antiretroviral treatment, the Affordable Resistance Test for Africa (ART-A) program is developing a less costly and less technical resistance test for resource limited settings. ‘The programs are really one of the best things in the HIV arena. They help us to understand what we are dealing with. Not only to monitor the magnitude and type of resistance at a population level, but also to be able to help the patient with the best treatment options as well. These programs improve clinical patient management and will make 2nd and eventually 3rd line treatments more effective.’

Exhausting all options

When talking to Dr. Rossouw it becomes clear that every fully resistant patient is one too many ‘It really breaks your hart to see patients who have exhausted all options. They are just like you and me, who perhaps made one bad choice in their life.’

She is however, not someone who gives up easily and she tries to find other means to help these patients. ‘A couple of years ago when patients exhausted all options we would give them a mix of all available drug therapies in the hope that some might still have a little effect. It is not ideal and really toxic. Or I would try to get them into a clinical trial, to get them on new experimental medication that could be effective. Only it has become much more difficult to get them in these trials now. We recently have started experimenting with a combination of indinavir and lopinavir/ritonavir (alluvia®) as a double boosted PI combination.’ In Europe or the US, there are many more treatment options with new generation drugs. Unfortunately these drugs are too expensive and not available in African settings.

Dr Rossouw understands that these solutions are probably not long-term ones and patients seem to react differently to these options: ‘Lenah, a woman in her midst thirties seems to respond quite well. It’s still early days but her viral load results look promising.’ She explains that Lenah is a classical case. There are many Lenah’s in South Africa who followed the same route to developing resistance strains. She started her treatment in a private clinic before the drugs became available in the public sector in 2004. The counselling in these clinics was not up to standard. So, whenever Lenah would run out of money she couldn’t afford to buy the medication. And because of the stigma that surrounds the disease she would hide the medication for her family, afraid to take it, when for example they would go on a trip together. By the time she came to Tshawane District Hospital it was hopeless, there was not much they could do for her anymore.

Another patient Freddy, 43 years old, is however not responding to this new combination. ‘Unfortunately he is not doing well’, says Dr. Rossouw. ‘He suffers from chronic diarrhoea and therefore has problems absorbing the medication.’ Freddy’s story is really a sad one. He has no family support; he is completely on his own. His monthly visit to the clinic 60 kilometres away is his only support. Through a lack of help he went off his 1st line medication. If he becomes ill he had no one to fetch his medication. And because he developed chronic diarrhoea he lost his 2nd line as well. His body was unable to absorb the medication. ‘We tried everything to cure his diarrhoea.’

Developing resistance

The example of Freddy is a good illustration of how resistance is often caused through unfortunate circumstances that are beyond the patient’s control. “It happens far too often that people are blamed for their treatment failure. You had your chance and you screwed it up! However, there are a lot of other reasons why someone fails or decided to stop taking pills’, explains Dr. Rossouw, ‘and mostly they have nothing to do with blame.’  Drug stockouts, and adverse drug interactions (interactions of HIV drugs with other drugs that make them less effective, e.g. drugs for TBC or epilepsy), are major causes why patients develop resistance. But there are also issues like deliberate non-adherence: ‘An example is a teenage girl who just turned 17 and who decided to stop her medication. She was angry with her mother, with her doctor, with her medication. She wanted to be normal, which is completely understandable, but with this anger she ruins her life. This anger is something we see with a lot of teenage people.’

Often non-adherence is caused by underlying social economic factors, simply because people don’t understand the problem and are less aware of the risk of not taking their medication in time. ‘Last week a teenage girl with her HIV infected baby came in. The mother of the 15 year old girl is working full time, so the daughter was responsible for the medication of the baby. But she can hardly take care of herself, let alone her baby. Consequently, the baby therefore already failed her medication.’

The pandemic in South Africa

These types of issues certainly will speed up the development of HIV drug resistance in the South Africa population. South Africa is the most HIV-affected country in the world, with over 5,5 million people infected (15.5% of the population). But Dr. Rossouw is glad to see that her government has lately made quite a few changes to combat the pandemic. It has at the policy level finally accepted HIV as cause of AIDS and it has adopted new policies to make medication more accessible. Already 800,000 thousand people in South Africa are on treatment, which will hopefully be scaled up by another million in the next years. However, more treatment will mean more resistance in the population. Systematic tests for HIV resistance remain unaffordable for the time being and will certainly not be integrated in the basic healthcare package. 

Although Dr. Rossouw worries about the mounting problem of the lack of well trained medical staff in South Africa, the thing that really upsets her is the South African Prevention of Mother-to-Child Transmission (PMTCT) policy: ‘Pregnant women, who do not qualify for HAART according to the policy i.e. CD4> 250, are exposed to single dose nevirapine therapies for between 12 and 26 weeks instead of HAART like in westerns counties. Simply because of the costs.’ The policy has to protect the mother and the child, but the effect of this single dose is that it only temporarily lowers the viral load and thus mothers can still infect their newborn babies through breast-feeding. Moreover, because the drug stays long in the blood at sub-optimal levels, the chance that resistant strains develop, both in mother and child is looming. ‘The resistant viruses stay in the body of the child, which means that the most common treatment options by HAART are no longer relevant for them.  ‘Suppressing viral load in children is really difficult, a child’s body interacts differently with the virus ’ clarifies Dr. Rossouw, “because a child’s immune system is not mature yet”. Resistance test for children are therefore even more vital to understand how the virus mutates and provide better clinical care. Each year in South Africa between 30,000 and 60,000 newborns are infected in this way; completely unnecessary!’ She worries for this new HIV positive generation. The direct result is that maternal and infant mortality rates have gone up again. South Africa will not reach the millennium goals on child and maternal health.