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The
New York Patient: A Harbinger of Super Aggressive HIV?
New York City health officials announced on February
11, 2005 that a patient rapidly developed full-blown AIDS shortly
after being diagnosed with a rare, drug-resistant strain of HIV-1.
The New York City Department of Health issued an alert to all hospitals
and doctors and a press conference was held to announce the emergence
of an aggressive HIV-1 strain that may be difficult to treat and
that appears to trigger rapid
progression to AIDS.
Is
the panic justified?
The
two phenomena of rapid disease progression and multi-drug
resistance, which are combined in the aggressive HIV-1
strain, are not unique. HIV-1 causes a persistent infection and
this virus is generally not a fast killer.
Within
the Amsterdam Cohort Studies on HIV-AIDS, it takes on average 8.3
years from the time a person is first infected with HIV-1 for AIDS
to develop, and another 17 months from AIDS to death.
However, the length of the incubation period varies from 2 months
to more than 20 years.
Cases
where it takes much shorter are not uncommon (rapid-progressors),
and likewise there is a significant group of so-called long-term
non-progressors.
There
seems uncertainty about the actual date of infection of the New
York individual, such that AIDS may actually not have developed
within 2 to 3 months, but rather within 20 months, which makes this
case less exotic.
Transmission
of a drug-resistant HIV-1 variant is not uncommon either. The number
of cases has remained relatively small, but may be on the rise due
to an increase in therapy failures.
The
New York virus appeared resistant to three classes of antivirals
(the reverse
transcriptase inhibitors (NRTIs); nucleoside and non-nucleoside
drugs (NNRTIs), as well as protease
inhibitors), but this is not unexpected either in the
era of combination-therapy in which therapy failure will usually
mean the emergence of multi-drug resistant HIV-1 variants.
Drug-resistant
HIV-1 variants usually have reduced replication capacity compared
to a wild-type virus due to the mutations in the reverse transcriptase
and protease enzymes. This loss in replication
fitness may be even larger for a multi-drug resistant
virus.
How
does this relate to the aggressive disease course? More research
is needed to resolve this issue. First, it is not always true that
the acquisition of drug-resistance mutations causes a fitness loss.
Even in case a loss is apparent, the virus may select compensatory
changes over time, and the end result may in fact be a virus variant
with increased replication fitness.
Second,
one can only link a particular pathogenicity phenotype to a virus
strain when a distinct disease pattern is seen in multiple infected
persons. When an isolated case is discussed, it is equally possible
that the particular disease pattern is not due to the virus, but
rather due to a special property of the infected human host. Person-to-person
variation in the immune system or other factors that interact with
HIV-1 (receptors, innate immune factors etc) can greatly influence
disease progression.
The
authors note in conclusion, ”Overall, this case seems relatively
rare but not necessarily alarming. Increased attention is not necessarily
bad, but press conferences should be reserved for situations when
a cluster of such transmissions is apparent.”
“The
current hype about super aggressive HIV-1 strains seems unfounded.”
Department of Human Retrovirology,
Academic Medical Center, University of Amsterdam, Amsterdam, the
Netherlands.
04/06/05
Reference
B
Berkhout, A de Ronde and L van der Hoek. Aggressive HIV-1? Retrovirology
2: 13. Published online February 28, 2005.
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