Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy

Abstract

In HIV-1-infected individuals on currently recommended antiretroviral therapy (ART), viremia is reduced to <50 copies of HIV-1 RNA per milliliter, but low-level residual viremia appears to persist over the lifetimes of most infected individuals. There is controversy over whether the residual viremia results from ongoing cycles of viral replication. To address this question, we conducted 2 prospective studies to assess the effect of ART intensification with an additional potent drug on residual viremia in 9 HIV-1-infected individuals on successful ART. By using an HIV-1 RNA assay with single-copy sensitivity, we found that levels of viremia were not reduced by ART intensification with any of 3 different antiretroviral drugs (efavirenz, lopinavir/ritonavir, or atazanavir/ritonavir). The lack of response was not associated with the presence of drug-resistant virus or suboptimal drug concentrations. Our results suggest that residual viremia is not the product of ongoing, complete cycles of viral replication, but rather of virus output from stable reservoirs of infection.

Fig. 1.

Intensification does not reduce residual viremia in patients on ART. (A) Median HIV-1 RNA levels of the 5 JHH patients at multiple sampling points before, during, and after intensification with ATV/r. (B) Levels of viremia in the JHH patients intensified with ATV/r. (C) Median HIV-1 RNA levels of the 4 NIH patients at multiple sampling points before, during, and after intensification with EFV and LPV/r. (D) Levels of viremia in NIH patients intensified with either EFV or LPV/r. Open symbols represent measurements below the limit of detection (1 copy per milliliter).

Fig. 2.

ART intensification does not reduce HIV-1 viremia. HIV-1 RNA levels for all time points for all 9 patients. Each set of colored symbols represents HIV-1 RNA values obtained for the indicated patient during each phase of the study and corresponds to the symbols used in Fig. 1. Open symbols represent measurements below the limit of detection (1 copy per milliliter). Levels of viremia during intensification were not statistically different from preintensification and postintensification levels.

Fig. 3.

Therapeutic concentrations of intensifying drug were achieved during the intensification period. (A) ATV. (B and C) EFV. (D) LPV. Open symbols represent measurements below the LOQ for respective drugs.