CASCADE study suggests HIV has increased in virulence and transmissibility

15 Dec 2014

Results from the CASCADE project strongly suggest that HIV has increased in virulence and transmissibility, at least in Europe, since the virus came to light at the end of the 1970s. This research was published in the Lancet HIV in November 2014. 

HIV is a virus with high genetic diversity.  As the HIV virus reproduces, slight variations in the genetic structure of the virus begin to occur.  Over time, this means that there will be several subtypes of HIV, and each subtype may be more or less able to cause illness.  The term used to describe a virus’ ability to cause illness is virulence.  If someone is infected with a more virulent form of HIV they will become ill more quickly.  Additionally, more virulent forms of HIV may increase the risk of the virus being transmitted (passed on) to others. 

The CASCADE collaboration is a network of researchers from 14 countries, sharing data from 29 different groups of HIV-positive individuals. Through pooling data, the CASCADE researchers are able to answer questions that cannot reliably be answered by smaller studies alone.

The CASCADE researchers used data from 15,875 HIV positive people from across Europe and beyond.  In order to track changes in HIV virulence over time, the researchers looked at specific points in HIV infection before the beginning of treatment for each patient, including:

  • Each patient’s CD4 cell count at seroconversion.  Seroconversion is the earliest point at which we are able to detect that a person’s body is beginning to fight the HIV virus.  CD4 cell count shows how well a patient’s immune system is working: the higher the CD4 count, the better.
  • Each patient’s viral load set point (the amount of virus in each person’s blood at the point at which their immune system begins to try to fight the virus).  Higher viral load set points, increase the risk of developing AIDS and death in the absence of treatment.

The study found that CD4 cell count at seroconversion decreased over time and viral set point increased from 1980 until about 2002.  CD4 cell counts at seroconversion and viral set-point remained relatively stable thereafter. This translates to a typical individual infected in 2004 reaching a critically low CD4 cell count and therefore requiring treatment within 3.4 years, whereas an individual infected in 1980 would require treatment in 7 years.  Similarly, someone infected in 2002 would typically have a higher viral load set-point than someone infected in 1980, giving them a 44% higher risk of passing on HIV to others.

These findings provide strong indications that HIV virulence and transmissibility have increased over the course of the epidemic. 

The CASCADE findings are very different to those of another recently published study, which used data taken from HIV-infected people in Durban, South Africa and Gaborone, Botswana.  This study suggested that HIV in southern African was mutating over time into a less virulent form.  There are many possible reasons for these different results. 

CASCADE is part of EuroCoord, a Network of Excellence funded by the European Union, which allows the network members access to data from over 250,000 HIV positive people.  This observational study used data from EuroCoord, and was funded by the European Union Seventh Framework Programme. 

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