HIV infection can cause a specific sub-group of CD4 T-cells
to age by as much as 20 or 30 years within three years of contracting the
virus, American researchers report. This ageing process could help to explain
the unusual rate of diseases associated with the elderly in HIV-infected people
in their middle years, they speculate.
Cancers, cardiovascular disease and bone thinning (osteoporosis) have been observed either at high rates or at younger ages in people with HIV infection, leading to speculation that HIV infection and the inflammation associated with prolonged activation of the immune system by the virus may be the cause of the early onset of diseases of ageing in HIV-positive people.
Many of the conditions associated with ageing are influenced by the loss of immune function with age.
Some researchers have become interested in determining whether HIV has direct effects on the immune system that speed up the ageing process, effectively leaving a person with HIV infection with the immune system of a much older person.
T-cell ageing can be measured by looking at the ends of
chromosomes within the cells. The ends of chromosomes are protected by
telomeres, which stop them from being damaged or fusing together. As we age,
the telomeres become shorter. Eventually the telomeres become so short that the
cell ceases to function properly.
The study reported this week in the journal PLoS One, conducted by UCLA AIDS
Institute, shows that among people infected with HIV, two subsets of naïve CD4+
T cells show signs of telomere shortening equivalent to 20 to 30 years of
ageing within two to three years of infection.
A similar rate of ageing happened in younger (20-39) and
older (39-58) adults.
Patients also experienced a decline in the number of naïve
CD4+ cells in comparison to age-matched controls, even though this group of
CD4+ cells is not the primary target of HIV infection, nor the primary
sub-group depleted as a result of HIV infection. Indeed, this subset was more
depleted than any other subset of CD4+ cells.
Naïve CD4+ T-cells are needed to respond to new infections.
As we age, they become less plentiful, making it more difficult for the immune
systems of older people to respond to new infections they haven’t encountered
before. These cells are also needed to develop immunity after vaccination,
which is why elderly people are less likely to develop protection after
vaccination than younger people.
In adults with HIV aged 20-39 the naïve cell subset was 2.9
times smaller than in age-matched HIV-negative controls (p=0.0007). The
difference in this subset was not significant in those aged 39 to 58.
What’s more, the naïve T cell subset being studied (CD31-
CD4+) is not restored to normal levels for a person’s age
after they start antiretroviral treatment. Looking at a separate sample of
patients from the Multicenter AIDS Cohort Study, the researchers found that this
subset of CD4+ cells remained significantly smaller in HIV-positive people two
years after starting antiretroviral treatment.
The researchers speculate that the increased rate of some
cancers seen in people with HIV when compared to age-matched controls, as well
as a higher rate of some infections, may be due to the immune defects detected by
The researchers also suggest that accelerated HIV disease
progression in the over-50s could be a consequence of the additive effects of
HIV infection and of ageing on this CD4+ T-cell subset.
"Our findings have important implications for the health of both young and old
HIV-1–infected adults," said lead investigator Tammy M. Rickabaugh, an assistant
research immunologist in the division of hematology and oncology at the David
Geffen School of Medicine at UCLA. "They underscore the importance of developing
new approaches to boost immune function to complement current treatments, which
are exclusively directed against the virus."