AIDS experts at Johns Hopkins say they have compelling
evidence that some people with HIV
who for years and even decades show extremely low levels of
the virus in their blood never progress
to full-blown AIDS and remain symptom-free even without
treatment probably do so because of the
strength of their immune systems, not any defects in the
strain of HIV that infected them in the
Their conclusions about so-called elite suppressors,
published this month in the Journal of
Virology, come from rigorous blood and genetic studies
from a monogamous, married African-American
couple in Baltimore; the wife was infected through sex with
her husband more than a decade ago.
Unlike her husband, the wife remains symptom-free, has
consistently had viral counts of fewer
than 50 copies per cubic milliliter of blood and has not
needed any treatment to keep the disease in
check. The husband, as a so-called progressor, takes a
potent drug cocktail to keep his infection from
developing into full-blown AIDS, as demonstrated by viral
counts in the hundreds of thousands per
cubic milliliter of blood. The couple has been married for
two decades, and the husband was an
intravenous drug user.
The scientists say the case study disproves some
suspect theories about elite suppression that
suggest it always involves a defective or "weakened" viral
strain, which is easier for the immune
system to attack, or that genetic variants confer a
protective effect in suppressors.
"This is an extremely rare case of co-infection in a
controlled, monogamous relationship, which
showed us how a strong immune system in the elite
suppressor kept the virus from replicating and
infecting other cells," said senior study investigator and
infectious disease specialist Joel Blankson.
"Our findings offer hope to vaccine researchers
because they reveal that the immune system's
primary offense, known as CD8 killer T-cells, can
effectively halt disease progression by a pathogenic
form of HIV," said Blankson, an assistant professor at the
School of Medicine.
"Moreover, the strength of the immune response was not
dependent on infection by a weakened
form of the virus. And if we can harness the means by which
these elite white blood cells stop the
virus, then we can hopefully 'teach' or reprogram white
blood cells in others to also target HIV," he
Included in the blood analysis was genetic testing
that confirmed that both husband and wife
were infected with the same pathogenic strain of HIV and
ruled out the possibility that there were
genetic deficiencies in the virus that infected the
Genetic testing also confirmed that both husband and
wife had an overactive strand of genetic
material tied to gene HLA B57, found in previous studies to
be more common in those whose HIV
infection was suppressed or slowed.
"The presence of this genetic spot is a discordant
result that strongly contradicts theories
that various genetic factors alone play a protective role
in suppression," Blankson said.
He noted that study findings revealed a beneficial
side effect to spurring the immune system
cells to attack HIV.
Using new laboratory tests that precisely measure the
immune response to various strains of
HIV, researchers first tested T-cells from both the wife
and husband to see if their immune system
cells suppressed viral replication. They found that
activated T-cells from the wife stalled HIV
replication by as much as 90 percent, while the husband's
T-cells stopped it by only 30 percent.
In subsequent genetic analyses, the viral strain in
the wife's blood was found to have at least
two mutations known to weaken the virus, while the viral
strain in the husband's blood had fewer
mutations affecting fitness.
According to Blankson, the stronger immune system in
elite suppression not only lowers the viral
count in the body but also exerts selective, evolutionary
pressure on the original strain of HIV to
mutate away from the strong version that initially infected
the couple and toward weaker, less-fit
"Elite suppression offers clues to vaccine researchers
on many fronts: how CD8 killer T-cells
can attack HIV and how a stronger immune response can force
HIV into a permanent defensive state,"
Antibody-based HIV vaccines have generally failed to
work, and Blankson says a new approach is
needed and may be based on T-cell action.
He also plans to study differences in CD8 T-cells in
elite suppressors and progressors, with the
goal of retooling and activating T-cell action in
progressors to act more like those in elite suppressors.
Funding for this latest study was provided by the
National Institute of Allergy and Infectious
Diseases, a member of the National Institutes of Health.
In addition to Blankson, Johns Hopkins researchers
involved in these studies were Justin Bailey,
Karen O'Connell, Hung-Chih Yang, Yefei Han, Jie Xu,
Benjamin Jilek, Stuart Ray and Robert Siliciano.
Silicano is also a Howard Hughes Medical Institute
investigator. Additional assistance was provided by
Thomas Williams, of the University of New Mexico.