HIV drug resistance is inevitable. It is going to happen

‘The bottom line is that Asia is number two globally in the number of HIV infected people’, says Dr. Annette Sohn, director of the Therapeutics Research, Education, and AIDS Training in Asia (Treat Asia) network. It is estimated that around 5 million people in Asia are infected, which makes it the second hardest hit region by the HIV epidemic in the world, behind sub-Saharan Africa. ‘We therefore know HIV drug resistance is quite serious. It is inevitable; it is going to happen. In our cohort about 10 to 14 percent of the patients are already failing first line.’

Dr. Sohn refers to the TASER cohort. The TREAT Asia Studies to Evaluate Resistance (TASER) monitors acquired and transmitted HIV drug resistance in up to 10 countries across South, East and Southeast Asia. It is an important HIV drug resistance program which contributes to TREAT Asia goal to ensure the safe and effective delivery of HIV/AIDS treatments throughout Asia and the Pacific. It is further the Asian equivalent of the PharmAccess African Study to Evaluate Resistance (PASER), both part of the LAASER program to enhance the HIV/AIDS response in Asia and Africa. ‘What makes TASER unique is that no one in Asia is doing what we do; we are able to monitor and compare the effect of different treatments in multiple countries’, explains Dr. Sohn. The first conclusion that 10 to 14 percent of patients failing first line in the TASER cohort is higher than the first results of PASER. These results indicate that up to 7% of the PASER participants initiating highly active antiretroviral therapy (HAART) show signs of baseline resistance and over 24% in with a history of previous antiretroviral use.

Looming threat of resistance

In the interview Dr. Sohn was asked to give her expert opinion on the mounting problem of HIV drug resistance in Asia and on the importance of monitoring programs like TASER and PASER to effectively fight the threat.

‘We see resistance strains develop in many patients’, explains Dr. Sohn, who is a highly regarded paediatrician and researcher with extensive experience treating HIV/AID patients in Southeast Asia. ‘But the group that has the highest risk developing resistance strains are HIV patients with tuberculosis (TBC). The TBC medication has serious drug interaction with the antiretroviral drugs. Especially in India and Indonesia this has lead to a high percentage of patients failing first line.’ The drug interaction makes both their lifesaving drugs fail, often leading to death

However, what concerns her even more is the number of children failing their medication. ‘Children are following adult programs, but these are not going to work in children. In Thailand we have children at the age of five who already lack to respond to first line. Many at that age are already switched to second line. And in Thailand there is only limited access to third line. How can you guarantee that that will make it to their adolescence?  They will probably run out of options before they reach that age.’

For the above reasons monitoring the virus in the region is in her eyes crucial, in particular since genotyping at a patient level is not available in the public health systems in Asia: ‘Programs like TASER and PASER are vital in finding a way to block the development of resistance, to better understand how the virus mutates and to make informed decisions on the best treatment options. The clinical data we collect will provide evidence to help us communicate and advocate the problem. But it also helps us to predict what is coming. To answer questions like “what are we seeing?” and “why are patients failing sooner or later?” These results can help public health policy makers throughout Asia choosing the right health strategy and over time this will help protect HIV infected patients against resistance.’

Collaborating studies

Predicting what is coming and not just in Asia is in the eyes of Dr. Sohn the strength of the joined Asian and African studies under LAASER. This broad front plays an important role in collecting crucial evidence on a global scale. The results of the studies are an important contributor to global strategy for prevention and assessment of resistance of the World Health Organization (WHO). And TASER and PASER are joint members of HIVResNet, a working group with a steering committee of 35 international HIV drug resistance experts which advises the WHO policy makers in WHO’s global strategy on ways to tackle the danger of HIV drug resistance. The two studies furthermore reinforce one another by exchanging experiences and results and TASER teams give training in African clinics in data collection.
Dr. Sohn hopes that this collaboration can be expanded with a joined HIV drug resistance study in children. PASER has recently started enrolling HIV infected children for a children cohort in Uganda and Dr. Sohn would very much like a similar program being rolled-out in Asia. ‘Like in Africa, no data exist in Asia on the development of resistance strains in children. We need to monitor the virus in children to get reliable information and data which can help develop lifesaving paediatric HIV medicines so that these children are able to reach adulthood.’

The epidemic in Asia

The region is the number two globally, but what is driving the HIV epidemic in Asia is different from how the pandemic overrun sub-Saharan Africa. ‘In Asia the virus is concentrated in high risk group’, explains Dr. Sohn. ‘The major drivers of the virus are injecting drug users, sex workers and men who have sex with men (MSM). Furthermore, most countries in Asia have a reasonably functioning public health infrastructure, combined with governments that are committed to fight the HIV epidemic. In Malaysia, for instance, the government pays for antiretroviral therapies for all HIV infected patients.’ HIV has therefore not spread to the population like in sub-Saharan Africa.

The impact of the epidemic in Asia should nevertheless not be underestimated. According to the Independent Commission on AIDS in Asia AIDS remains the most likely cause of death and loss of work days among people aged 15 to 44 in the region. And although the virus is now still mostly concentrated in these three groups, Dr. Sohn warns for the high risk of expansion to the general population. ‘This is what happened in Thailand, sex workers infected their clients who in turn brought the virus home and infected their wives.’ A risk that is enlarged by the fact that the groups are difficult to reach because of he stigma that surrounds the illness, ‘Especially the MSM group has to deal with a great deal of discrimination, which denies them access to care and obstructs effective surveillance.’

Transmitted resistance

Another danger of this isolation is that within the group HIV resistance is sexually transmitted. Due to the lack of access this group is not monitored enough, with the risk that they stay on a failing therapy too long.  Because of the failing regime, the amount of drug resistance strains in their body increases, which they can transmit to other persons. ‘We think that transmitted HIV drug resistance is circulating in the MSM group, it is a high risk group, especially in the urban centres, like Bangkok’, says Dr. Sohn. ‘But because of the lack of surveillance of this group, there is only a limited amount of data available. We have tested some people, but not enough to fully underpin this thought. We therefore want to do a study just in the MSM population in Bangkok to understand the full scale of the problem and to fight it before it spreads even further.’