Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy

*HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702-1201;
^‡Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064;
^§University of Pittsburgh, Pittsburgh, PA 15260; and
^¶Tufts University, Boston, MA 02111

Contributed by John M. Coffin, January 4, 2008 (received for review December 16, 2007)

Abstract

Residual viremia can be detected in most HIV-1-infected patients on antiretroviral therapy despite suppression of plasma RNA to <50 copies per ml, but the source and duration of this viremia is currently unknown. Therefore, we analyzed longitudinal plasma samples from 40 patients enrolled in the Abbott M97-720 trial at baseline (pretherapy) and weeks 60 to 384 by using an HIV-1 RNA assay with single-copy sensitivity. All patients were on therapy (lopinavir/ritonavir, stavudine, and lamivudine) with plasma HIV RNA <50 copies per ml by week 96 of the study and thereafter. Single-copy assay results revealed that 77% of the patient samples had detectable low-level viremia (≥1 copy per ml), and all patients had at least one sample with detectable viremia. A nonlinear mixed effects model revealed a biphasic decline in plasma RNA levels occurring over weeks 60 to 384: an initial phase of decay with a half-life of 39 weeks and a subsequent phase with no perceptible decay. The level of pretherapy viremia extrapolated for each phase of decay was significantly correlated with total baseline viremia for each patient (R ² = 0.27, P = 0.001 and R ² = 0.19, P < 0.005, respectively), supporting a biological link between the extent of overall baseline viral infection and the infection of long-lived reservoirs. These data suggest that low-level persistent 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.

Footnotes

^†To whom correspondence may be addressed at:
HIV Drug Resistance Program, National Cancer Institute, 1050 Boyles Street, Building 535, Room 109, Frederick, MD 21702-1201.
E-mail: spalmer{at}ncifcrf.gov
^‖To whom correspondence may be addressed. E-mail: john.coffin{at}tufts.edu
Author contributions: S.P., F.M., B.B., G.J.H., S.C.B., D.J.K., J.W.M., J.M.C., and M.S.K. designed research; S.P. and A.W. performed research; B.B., G.J.H., S.C.B., D.J.K., and M.S.K. contributed new reagents/analytic tools; S.P. and M.S.K. analyzed data; and S.P. and M.S.K. wrote the paper.
The authors declare no conflict of interest.
Freely available online through the PNAS open access option.