The genetics of HIV-1 resistance

October 2, 2012

Drug resistance is a major problem when treating infections. This problem is multiplied when the infection, like HIV-1, is chronic. New research published in BioMed Central's open access journal Retrovirology has examined the genetic footprint that drug resistance causes in HIV and found compensatory polymorphisms that help the resistant virus to survive.

Currently the strategy used to treat HIV-1 infection is to prevent viral replication, measured by the number of in the blood, and to repair the immune system, assessed using CD4 count. Over the past 20 years treatment and life expectancy have vastly improved. However, due to drug resistance, complete requires an array of drugs.

For the virus drug resistance comes at a cost. In the absence of the drug the virus carrying is less 'fit' than the wild-type virus and so should not be able to replicate as efficiently. During interruptions to treatment wild-type viruses quickly predominate. However newly infected people can be drug resistant even before they have received any treatment.

Researchers from the SPREAD project have been monitoring HIV infections across Europe. This multinational team has looked at 1600 people, newly infected with HIV-1 subtype B. Almost 10% of these patients had HIV-1 harbouring transmitted drug resistance (TDR) and worryingly, when they measured and CD4 count, there was no indication that these strains of HIV-1 were weaker.

In recent years there has been much talk about polymorphisms, naturally occurring differences in the genes that are responsible for the differences between animals of the same species, for example blood groups or the ability to digest lactose in milk. They may also increase propensity for certain diseases including cancer and type 2 diabetes. But animals are not the only organisms that harbour polymorphisms – they are present in viruses as well.

By examining polymorphisms in these strains of HIV-1 the researchers discovered that certain polymorphisms in the gene coding for protease (essential for ) known to act as compensatory mechanisms, improve the 'fitness' of resistant strains, even in the absence of the drug. Kristof Theys, one of the researchers involved in the project commented, "Our worry is that over time we will be seeing more people presenting with TDR HIV-1."

Prof Anne-Mieke Vandamme, who led this study, fears "Contrary to what was expected, transmission of TDR virus may also contribute to a 'fitter' and more virulent HIV, which has important clinical implications in how we best treat these people."

Explore further: Drug designer: New tool reveals mutations that cause HIV-drug resistance

More information: Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients, Kristof Theys, et al. Retrovirology, (in press)

Related Stories

Recommended for you

Team tests best delivery mode for potential HIV vaccine

June 20, 2017

For decades, HIV has successfully evaded all efforts to create an effective vaccine but researchers at The Scripps Research Institute (TSRI) and the La Jolla Institute for Allergy and Immunology (LJI) are steadily inching ...

Understanding HIV's persistence

June 19, 2017

Most cells in the human body have a limited lifespan, typically dying after several days or weeks. And yet, HIV-1 infected cells manage to persist in the body for decades. Current treatment for HIV is very effective at suppressing ...

Researchers uncover clues about how HIV virus mutates

June 1, 2017

A new study published in Cell Host & Microbe led by researchers at Fred Hutchinson Cancer Research Center completely maps all mutations that help the HIV virus evolve away from a single broadly neutralizing antibody, known ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.