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Viral Dynamics of Elite Suppressors in HIV-1 Infection
Jason Dinoso*1, S Kim1, J Blankson1, and R Siliciano1,2
1Johns Hopkins Univ Sch of Med, Baltimore, MD, US and 2Howard Hughes Med Inst, Baltimore, MD, US
Background: HIV-1-infected patients who control
viremia without treatment (elite suppressors) and patients on
suppressive HAART-regimens both have viral loads below the clinical limit of
detection, 50 RNA copies per mL of plasma (copies/mL). In patients on HAART,
viremia reaches a stable plateau of ~3 RNA copies/mL. Low-level viremia in
elite suppressors has been detected but not quantified. We hypothesize that
viral loads in elite suppressors would be higher than in HAART-suppressed
individuals.
Methods: Through the use of an ultrasensitive
real-time polymerase chain reaction (PCR) -based viral load assay with a limit
of quantification of 8 copies/mL, viral loads from 8 individuals on
suppressive HAART were measured and compared with viral loads from 11 HAART-naïve
elite suppressors. For 6 of the elite suppressors, a repeated viral load
measurement was to determine whether there were large fluctuations over time. In
a longitudinal analysis, viral loads from 1 elite suppressor and 1 patient on
HAART were measured over time to determine if their viral dynamics represented
a steady-state.
Results: In the HAART-treated group, all 8 patients
demonstrated viral loads below 8 copies/mL; 4 of those individuals had
detectable plasma virus. Among the elite suppressors, 8 out of the 11 patients
had viral loads below 8 copies/mL; 2 of those individuals had detectable virus.
The remaining 3 elite suppressors with quantifiable viral loads had
measurements of 48, 87, and 25 copies/mL. Of the 6 elite suppressors that had a
second viral load measurement, 5 had viral loads below 8 copies/mL at both time-points
and the remaining elite suppressor had an increase in viral load from 25 to 62
copies/mL (0.4 log10 difference). In the longitudinal analysis, the
HAART-suppressed individual remained below 8 copies/mL and had detectable virus.
In contrast, the elite suppressor’s viral load fluctuated between 12 and 48 copies/mL
(0.6 log10 difference).
Conclusions: We provide preliminary data on viral
dynamics in elite suppressors. Compared with patients on suppressive HAART,
elite suppressors demonstrated a greater range of viral loads. In 1 elite
suppressor, the viral dynamics did not appear to follow a steady-state, but
rather underwent significant changes (>0.3 log10 copies/mL). Both
phenomena may reflect the varying degrees of ongoing replication occurring in
the absence of ART or the rate at which virus-producing cells are being cleared
by the immune system.
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