Drug resistance

Resistance to AIDS drugs in untreated people in eastern Africa has risen to more than 7 percent in the past decade. In western and central Africa, resistance rates rose to between 3.5 and 7.6 percent over a similar period.

These are the findings of a new study funded by the Bill & Melinda Gates Foundation and the European Union. Compiled by Silvia Bertagnolio of the United Nations' World Health Organization and Ravindra Gupta, a Wellcome Trust clinical research fellow at University College London, it was published in leading medical journal The Lancet to coincide with the 2012 Washington AIDS Conference this week.

The researchers say current resistance rates could "jeopardize a decade-long trend of decreasing HIV/AIDS-related illness and death in low and middle income countries."

Co-author Gupta says HIV/AIDS drugs programs in resource-poor countries need to focus on monitoring drug resistance rates, as well as providing the drugs in the first place.

DW: Dr. Ravindra Gupta, what are the hard facts of your study?

Ravindra Gupta: The hard facts of the study are that since anti-retrovirals were rolled out in Sub-Saharan Africa, there has been an increase in drug resistance in untreated patients and the greatest increases have been happening in eastern Africa and to a lesser extent southern Africa.

And to a significant extent over the last eight years - that's what we're talking about, isn't it?

Yes, well, rollout happened in different years in different countries, so that's why we haven't really been able to attach very hard dates. So, for example, on average in East Africa rollout happened quite early, between 2000 and 2003, whereas in southern Africa it is more like 2003 and 2004. So, really, it's over the last decade that drug resistance rates have been increasing. And that's in particular for one class of anti-retrovirals, which is the non-nucleoside drugs [non-nucleoside reverse transcriptase inhibitors - NNRTIs]. And these are the cornerstone of any therapy, so this is one of the most important drug classes.

And as I understand it, these are also drugs used to prevent transmission of the virus from a pregnant woman to an unborn child – and that would probably present a very serious threat to the United Nations' goals of reducing the number of babies born with HIV, wouldn't it?

Potentially, yes. Nevirapine is the drug that's used for preventing vertical transmission [mother-to-child transmission], and this is the class that we're concerned about. The levels we've seen are about 5 percent for the non-nucleoside drugs. What the WHO [World Health Organization] are moving towards is to get mothers onto anti-retroviral therapy during their pregnancy - to give them three drugs instead of just a single drug. And that decision may be influenced by the amount of resistance because non-nucleosides are part of those regiments. So, we're probably going to be using a class of drugs called protease inhibitors in pregnant women in the future. The UN goals could still be achieved if we take this into account.

So, can you explain what we're seeing here - that these rates have remained stable throughout this period?

Well, we've done an analysis over time - we have data from each year since the rollout happened. So, we've been able to model this over time. And certainly the East Africa data suggests that the [resistance] rates are increasing over time. And the increases are much gentler for southern and western Africa.

What needs to be done now? What are the immediate implications for the science behind the research into HIV/AIDS drugs?

We have a good array of drugs that are available, so the question in the developing world is what do we do next? And in the developing world there are only two lines of treatment - first and second line - so, the range of drugs is much more limited and that's why there's a problem. You know, we have high rates of drug resistance in the UK in untreated patients, but the fact is that we do baseline resistance testing and we have a much wider range of drugs to choose from - so, we can tailor therapies to people. But in the resource-poor world that doesn't happen. Everyone gets the same combinations of drugs. So, that's the real research agenda issue for the developing world - to decide how to screen patients for drug resistance at baseline.

But you have said that if these rates do continue to rise, that would jeopardize all the work so far.

Yes, it could jeopardize some of the gains made so far if resistance rates continue to increase and we don't do anything about it. So, that's true. What this data calls for is increased surveillance in Sub-Saharan Africa in particular. We need to be collecting resistance data and we're calling for a strengthening of systems to ensure that surveillance is a priority for these programs of retroviral delivery, so we can really keep an eye on this problem. And at the moment, surveillance is not the top priority of many treatment programs. The pressure is on just getting people on medication. What we're saying is that we need to make drug resistance surveillance integral to this effort.

Dr. Ravindra Gupta was among 20,000 delegates at the AIDS 2012 Conference in Washington.