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

TLDR

Residual viremia is detectable in most HIV‑1–infected patients on antiretroviral therapy despite plasma RNA <50 copies/ml, yet its source and duration remain unknown. The study examined longitudinal plasma samples from 40 patients to assess the persistence and dynamics of low‑level viremia using a single‑copy HIV‑1 RNA assay. Patients received lopinavir/ritonavir, stavudine, and lamivudine and were monitored with a single‑copy assay from week 60 to 384, with plasma HIV RNA <50 copies/ml by week 96. Seventy‑seven percent of samples showed detectable low‑level viremia, with a biphasic decline (half‑life ≈39 weeks then plateau) and pre‑therapy viremia correlating with baseline levels, indicating two reservoirs—one decaying and one stable for at least seven years.

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.