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Why Dolutegravir Might Get Us Closer to Ending AIDS: Next Step, Further Research

October 26, 2015

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Why Dolutegravir Might Get Us Closer to Ending AIDS: Next Step, Further Research

This blog discusses the implications for HIV-positive people of several studies at the 15th EACS conference in October 2015.


Introduction

Last week at the 15th European AIDS Conference (EACS) in Barcelona, several research groups -- from Argentina, France, Spain and the Netherlands -- presented results from small independent pilot studies that have the potential to dramatically change HIV globally.

If the early results are supported by larger studies, the implications include the potential:

  • To improve the quality of life by using fewer drugs associated with less side effects. Perhaps only one drug might be needed which already has one of the lowest risks of side effects.
  • To reduce costs of antiretroviral treatment (ART) at a time when health budgets are being cut in many high-income countries, including the UK, and when funding programmes for low and middle-income countries have a new challenge to double the number of people accessing ART.
  • To improve the choices of treatment worldwide. This is not just related to cost but to speeding up access to better second-line and first-line drugs.
  • To speed up the option to treat HIV with a long-lasting injection instead of daily pills medication. This might be possible to use one injection every three months. Until now, the concern to avoid drug resistance to dolutegravir has meant that researchers have been preoccupied with developing two injectible drugs to use in combination.
  • To play a new and unexpected role in research into either a cure or long-term HIV remission. This is really jumping ahead but might be an outcome if the mechanism to explain the early results is that dolutegravir disables HIV in a way that makes it unable to replicate.

But these remarkably grand hopes need to be tempered with serious caution and patience. The current results are tentative, short-term and in small numbers of people. The results are exciting because our understanding of the dynamics of HIV mean that they shouldn't have happened, but they did -- and coming as a surprise means that even experts are unsure of their significance.

Further research will be essential before trying this at home or even trying this with your doctor's advice. This is because these risks are serious too: dolutegravir might for example cause HIV to mutate in a way that makes the virus more difficult to treat, even with drugs that were working beforehand.

Larger studies are already planned or ongoing. Perhaps within a year the long-term outlook for treatment might be different for a significant percentage of HIV-positive people.


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What Were These Studies at EACS?

The studies all looked at whether HIV antiretroviral treatment (ART) could be simplified from standard 3- 4 drug combinations to using fewer drugs. The studies all used dolutegravir -- the most recently approved HIV drug -- either with one of the earlier HIV drugs called lamivudine (3TC), or using dolutegravir on its own. Three of the studies were in the same oral sessions that will hopefully be webcast.1

Dolutegravir belongs to a class of drugs called integrase inhibitors, which is probably one of the most effective drugs to reduce viral load and also has a low risk of side effects. 3TC is still widely used, and it is also very well tolerated with very few no side effects. Because 3TC came off patent several years ago, generic versions are available very cheaply in all countries.

Treatment with only one or drugs is not a new idea -- but until now results have never been able to matched results using three active drugs. So the current studies were therefore carefully designed to include very close and frequently monitoring, especially for viral load. The people taking part often had complications with HIV drugs that they were already taking due to difficult side effects, lack of available treatment or complicated drug interactions with other important medicines. So there were clinical reasons to consider this experimental approach based on individualised care.

Three studies at EACS 2015 used 50 mg dolutegravir in a two-drug combination with 300 mg lamivudine (3TC). Both drugs were taken together, once-daily, with or without food. On of these studies was in people starting treatment and two were in people switching. Four other studies used 50 mg dolutegravir as a single drug -- i.e., with no other HIV meds.

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This article was provided by HIV i-Base. Visit HIV i-Base's website to find out more about their activities, publications and services.
 

 

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