Interview: Anne Wensing on HIV resistance
Could you tell us a little about your background?
I became interested in the HIV virus while I was training to be a doctor. Once I was working as an infectious diseases specialist, I found I was particularly keen to understand how HIV developed resistance. Because I also enjoyed carrying out research, I ended up combining research with clinical virology.
What do you find so interesting about the HIV virus?
Viruses represent evolution in a nutshell, allowing you to study evolutionary processes in a short space of time. This rapid evolution is what particularly interests me about HIV, as well as its far-reaching societal implications.
You were involved in setting up the European Society for Translational Antiviral Research and are actively involved in mapping HIV resistance in Europe. Could you explain a little more about the mechanisms of HIV resistance and your work in this field?
As part of this group, I looked into the transmission of resistant HIV viruses. In addition, I am now investigating transmission networks, risk factors and mechanisms of resistance. Another area of interest is the accumulation of resistance, especially in Africa.
Over the years, we have seen that there are a number of problems linked to resistance. For example, resistance is strongly related to treatment compliance. If medication is not taken or not taken properly, the virus has the chance to form a resistant version, which can subsequently multiply. Furthermore, because we are seeing increasingly less resistance in the Netherlands, doctors have fewer opportunities to acquire knowledge about patterns of resistance evolution. However, this knowledge is important to enable accurate estimates of resistance and to mount an appropriate response to resistance. Baseline resistance is an additional issue, particularly amongst men who have sex with men, as is inadequate monitoring, for example in Africa. At present, in Africa, any virological monitoring that does take place tends to look only at the patient’s viral load and, if it’s too high, the medication is switched. Switching too quickly to second-line therapy may cause problems for the patient, since these second-line medications often have more side effects. Furthermore, it is more difficult to tailor second line therapy to resistance profiles, which limits future options. More extensive monitoring could avoid these issues.
I am happy to say that, in the Netherlands, resistance is under control due to proper monitoring, specialised doctors and nurses, as well as therapies tailored to the patients. All in all, this ensures that patients have high viral suppression and, if things do start to go wrong, we are able to take action at an early stage, thereby allowing very little accumulation of resistance.
In addition to treatment compliance, what are other possible causes of resistance?
Apart from poor treatment compliance, another important cause of resistance is interaction with other medication. Given that we don’t have an infinite number of drug combinations at hand, it is very important in both cases that patients are sufficiently treatment compliant and that they inform their treating physician about any other medications they may be taking.
Are resistant viruses transmissible?
Yes, resistant viruses are transmissible, albeit at a lower rate. Resistant viruses are not only less capable of multiplying, but they are also less capable of generating new infections. However, there are certain resistance patterns that compensate for the loss in ‘fitness’, and viruses with these particular patterns have been found to be more effectively transmitted. The fact that, in Europe and the USA, 10% and 20%, respectively, of treatment-naive patients carry a resistant virus clearly indicates that these viruses can be transmitted.
In an interview with Loek Elsenburg elsewhere in this newsletter (click here), we discussed the current trend in the Netherlands to reduce the number of patient visits. Do you think this could lead to more resistance?
The population in the Netherlands has been receiving treatment for a long time now. Providing they maintain the routine and discipline in taking their medication properly, I don’t foresee any resistance problems. However, it is very important to be alert during the first period of infection; in Africa we have shown that failure to monitor can lead to problems.
How does knowledge about medication resistance help patients and treatment teams to further optimise the therapy?
We have gained a lot of knowledge, as a result of which in the Netherlands we have achieved a high level of HIV suppression with second-line therapy. This is, in part, because we always select this therapy on the basis of resistance patterns. In addition, we now know that it is important to use drugs more strategically, and this has yielded far more drug combinations.
Do you also see resistance in the treatment of hepatitis B (HBV) or hepatitis C (HCV) and HIV con-infection?
Yes, this resistance occurs with both HBV and HCV. In the case of HCV, the length of treatment has been shortened dramatically by the new medications, and therefore the risk of resistance is also lower. However, if the medication is not taken properly or in the wrong combination (not all HCV drugs and HIV inhibitors can be combined), there is a high risk of resistance. In the case of HBV, resistance develops more slowly, partly because HBV is a DNA virus.
However, we don’t see more or less resistance in co-infected patients than in mono-infected patients, but the overall picture is more complex. Doctors have to have a good grip on the treatment of both infections, since HIV medication can interact with HCV drugs. This is why co-infected patients are usually treated by infectious disease specialists, who can take a broader view of it all. Moreover, co-infected patients also discussed within a multidisciplinary team, which is quite unique. In each treatment centre, infectious disease specialists, virologists, pharmacists and HIV nurse consultants come together to select a new therapy for both HIV mono-infected and co-infected patients with resistance. In the case of co-infected patients, consultation with the hepatologist or gastrointestinal physician is also very important.
How does SHM contribute to your research and work?
SHM’s overview of individual patients* is very important in my work. It allows me to see which drugs have already been used and what the toxicity profile was. Even if resistance measurements have not been carried out, I can still use the viral load pattern to trace whether resistance selection has taken place. In my opinion, this overview is essential in selecting the right treatment switch in patients with a long history; in other words, SHM’s data really help patients. In addition, we have also recently started a scientific collaboration with SHM: SHM is now helping to map HIV resistance in Europe and we are working to make resistance data more accessible in SHM’s database.
I hope this collaboration with SHM will continue. The information it yields is very important, and will remain so. One of the reasons why HIV care in the Netherlands is of such high quality is because we are able to so neatly map the history of patients, something in which SHM plays a crucial role.
*SHM’s patient-specific and centre-specific reports offer HIV treating physicians and nurse consultants insight into their own patient population, both at the total population and patient-specific level. For each registered patient, raw data are available that provide an overview of the course of the patient’s HIV infection. The centre-specific reports provide treatment centres with insight into the developments and trends within their own patient population and allow them to compare these with the general trends in the Netherlands. Both forms of reports can only be viewed by physicians and nurse consultants.