Low
Levels of HIV Persist for at Least 7 Years Despite Effective Antiretroviral Therapy  As
reported in the current (March 11, 2008) issue of the Proceedings of the National
Academy of Sciences USA, researchers from the National Institutes of Health,
Abbott Laboratories, Tufts University, and the University of Pittsburgh evaluated
residual HIV levels in patients undergoing prolonged antiretroviral therapy.
The
analysis included plasma samples from 40 patients enrolled in the Abbott M97-720
trial at baseline (pre-therapy) and at weeks 60 to 384, using an HIV-1 RNA assay
with single-copy sensitivity.
Measuring the level of persistent viremia
over 7 years in patients on suppressive anti-HIV therapy provided a unique opportunity
to examine the dynamics of low-level viremia in individuals responding well to
treatment.
All participants were on therapy with lopinavir/ritonavir (Kaletra),
d4T (stavudine; Zerit), and 3TC (lamivudine;
Epivir) and had achieved plasma
HIV RNA < 50 copies/mL by week 96 of the study and thereafter.
Results
•
Single-copy assay results revealed that 77% of the patient
samples had detectable low-level HIV viremia (at least 1 copy/mL).
•
All patients had at least 1 sample with detectable viremia.
•
A non-linear mixed effects model revealed a biphasic decline
in plasma HIV RNA levels occurring over weeks 60 to 384: an initial phase of decay
with a half-life of 39 weeks, followed by a subsequent phase with no perceptible
viral decay.
•
The level of pre-therapy viremia extrapolated for each
phase of decay was significantly correlated with total baseline viremia for each
patient, supporting a biological link between the extent of overall baseline viral
infection and the infection of long-lived reservoirs.
Conclusion
According
to the study authors, these findings suggest that low-level persistent HIV viremia
"appears to arise from at least two cell compartments, one in which viral
production decays over time and a second in which viral production remains stable
for at least 7 years."
The authors also noted, "The indication
that different cellular compartments contribute to persistent viremia in treated
patients has important implications for strategies to eradicate infection."
Finally,
they added, "Clearly, these compartments cannot be eliminated by standard
antiretroviral therapy, and new therapeutic approaches will be needed to eliminate
virus from long-lived reservoirs."
HIV Drug Resistance Program,
National Cancer Institute, National Institutes of Health, Frederick, MD; Global
Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL;
University of Pittsburgh, Pittsburgh, PA; Tufts University, Boston, MA.
3/14/08
Reference
S
Palmer, F Maldarelli, A Wiegand, and others. Low-level viremia persists for at
least 7 years in patients on suppressive antiretroviral therapy. Proceedings
of the National Academy of Sciences of the United States of America (PNAS).
March 10, 2008 [Epub ahead of print]. |
