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Low-level Virema in HIV-1-infected Patients Classified as Elite Controllers Compared to Patients on Suppressive ART
Sarah Palmer*1, A Wiegand1, T Miura2, B Block2, F Pereyra2, F Maldarelli1, J Mellors3, B Walker2, and J Coffin4
1HIV Drug Resistance Prgm, NCI, Frederick, MD, US; 2Partners AIDS Res Ctr, Massachusetts Gen Hosp, Boston, US; 3Univ of Pittsburgh, PA, US; and 4Tufts Univ, Boston, MA, US
Background: In a small proportion (5 to 10%) of HIV-1-infected
individuals immunodeficiency progresses slowly. These patients have CD4+
T cell counts of >500 cells/µL and some, known as elite controllers, have
very low plasma HIV-1 RNA levels, often undetectable by standard assays. In the
present study, we used a real time polymerase chain reaction (RT-PCR) assay
with single copy sensitivity to quantify and
compare plasma HIV-1 RNA levels in elite controllers to those in patients with
<50 copies/mL on suppressive ART.
Methods: Plasma samples from 46 elite controllers who had
three measured viral RNA levels of <50 copies/mL over at least a 1-year
period without treatment were analyzed. Their HIV-1 RNA levels were compared to
samples from 163 patients suppressed on therapy to <50 copies/mL for 4 to
333 weeks. Plasma samples were spiked with an internal virion control (RSV),
ultracentrifuged, extracted, and quantified in triplicate using real-time
RT-PCR. Results from samples with less than 50% recovery of the internal
control were censored.
Results: Viremia was detected in 75% of the samples from
both elite controllers (ranging from 1 to 614 copies/mL) and patients on
suppressive therapy (ranging from 1 to 43 copies/mL). The median HIV-1 RNA
value for the elite controllers and treated patients (irrespective of their
treatment regimens) was significantly different 5.5 and 3.0 copies/mL,
respectively (p = 0.023, 1-way ANOVA), and the overall distribution of
HIV RNA levels was significantly different (p = 0.013,
Kolmogorov-Smirnov test). Testing of longitudinal samples (3 to 7
samples/patient) from four elite controllers showed spontaneous changes in
viremia of 2- to 48-fold.
Conclusions: Similar to patients on suppressive
antiretroviral therapy, the majority of patients classified as elite
controllers have low-level viremia. The levels of viremia below 50 copies/mL
was higher for elite controllers compared to those in persons on suppressive.
The mechanisms involved in the virus suppression in elite controllers remain to
be elucidated.
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