The rapid evolution of HIV, which has allowed the virus to
develop resistance to patients' natural immunity, is at the same
time slowing the virus's ability to cause AIDS, according to new
research funded by the Wellcome Trust.
The study also indicates that people infected by HIV are likely
to progress to AIDS more slowly - in other words the virus becomes
less 'virulent' - because of widespread access to antiretroviral
therapy (ART).
Both of these factors make an important contribution to the
overall goal of the control and eradication of the HIV epidemic. In
2013, there were a total of 35 million people living with HIV
worldwide, according to the World Health Organization.
The research was carried out in Botswana and South Africa, two
countries that have been worst affected by the HIV epidemic. Across
those countries, researchers enrolled over 2,000 women with chronic
HIV infection to take part in the study.
The first part of the study looked at whether the interaction
between the body's natural immune response and HIV leads to the
virus becoming less virulent.
Central to this investigation are proteins in our blood called
the human leukocyte antigens (HLA), which enable the immune system
to differentiate between the human body's proteins and the proteins
of pathogens. People with a gene that expresses a particular HLA
protein, called HLA-B*57, are known to benefit from a protective
effect against HIV. HIV-infected patients with the HLA-B*57 gene
progress more slowly than usual to AIDS.
This study showed that in Botswana, where HIV has evolved to
adapt to HLA-B*57 more than in South Africa, patients no longer
benefit from this gene's protective effect. However, the team's
data show that the cost to HIV of this adaptation is that its
ability to replicate is significantly reduced, therefore making the
virus less virulent.
The authors show that viral adaptation to protective gene
variants, such as HLA-B*57, is driving down the virulence of
transmitted HIV and is thereby contributing to HIV elimination.
In the second part of the study, the authors examined the impact
of ART on HIV virulence. They developed a mathematical model, which
concluded that selective treatment of people with low CD4 counts
will accelerate the evolution of HIV variants with a weaker ability
to replicate.
Professor Phillip Goulder from the University of Oxford said:
"This research highlights the fact that HIV adaptation to the most
effective immune responses we can make against it comes at a
significant cost to its ability to replicate. Anything we can do to
increase the pressure on HIV in this way may allow scientists to
reduce the destructive power of HIV over time."
Dr Mike Turner of the Wellcome Trust, said: "The widespread use
of ART is an important step towards the control of HIV. This
research is a good example of how further research into HIV and
drug resistance can help scientists to eliminate HIV."
The paper, Impact
of HLA-driven HIV adaptation on virulence in populations of high
HIV seropervalence, is published in the Proceedings of
the National Academy of Sciences.