Johns Hopkins scientists say an infected
person's HIV subtype is a better predictor
than viral load for determining
rapid death from AIDS. Traditional testing
standards help monitor the progression of
an HIV infection to AIDS by keeping track
of viral load, using a scale in which less
than 50 viral particles per cubic milliliter of
blood is considered suppressed disease and
a viral load of more than 75,000 particles
per cubic milliliter of blood means that the
disease will progress more rapidly.
In what is believed to be the first analysis
of viral subtype as a predictor of death
from AIDS, which also takes into account
viral load, the Johns Hopkins team found
that having viral subtype D made a person
with HIV likely to die more rapidly compared
to a person with subtype A. Ten
percent of those infected with subtype
D died within three years, while none
with subtype A died. However, viral load
ranged from 20,000 particles per cubic
milliliter of blood to 100,000 particles
per cubic milliliter of blood in those with
both subtypes and was not found to be an
accurate predictor of rapid death within
the same timeframe.
Participants in the study came from the
Rakai cohort, a population of 12,000 people
in Uganda who are being monitored to
determine how HIV spreads throughout
the country. More than 300 newly infected
men and women participated in the study,
conducted between 1995 and 2001, with
53 becoming infected with subtype A and
203 infected with subtype D. Another 70
were infected with a recombinant version
of both subtypes. Even though the quantity
of virus infecting these individuals
was roughly the same for each subtype,
average years of survival for each subtype
differed widely: 8.8 years for A, 6.9 years
for D and 5.8 years for AD.
Through annual blood tests, which
were part of the study, the researcher
knew when each person became infected.
Once the diagnosis was confirmed,
researchers used DNA tests to determine
the HIV subtype, A and D being the
most common in Uganda.
Researchers believe that subtype D is
more virulent than subtype A because
D has the ability to bind to key receptors
on immune cells, allowing subtype
D to kill more quickly. Additional blood
analysis showed that with subtype A, the
virus bound only to one kind of receptor,
CCR5, to infect the cell. But 25 percent
of subtype D virus bound to both CCR5
and another receptor, CXCR4. Indeed,
two-thirds of those infected with CXCR4-
binding virus died within three years.
According to the study's lead researcher,
Oliver Laeyendecker, a research associate at
the Johns Hopkins School of Medicine and
senior research assistant at the National
Institute of Allergy and Infectious Diseases,
“Knowing a person's HIV subtype is important
for the management of the infection
because the disease can progress more rapidly
in those infected with subtype D and
recombinant virus incorporating subtype D
than in those with other subtypes."
The findings were presented at the 2006
Conference on Retroviruses and Opportunistic
Infections, held last week in Denver.
This talk and others by Hopkins faculty
can be viewed at www.retroconference.org/2006.