Residual viremia is preceding viral blips and persistent low-level viremia in treated HIV-1 patients

Abstract

Background: It has been suggested that low-level viremia or blips in HIV-infected patients on antiretroviral treatment are related to assay variation and/or increased sensitivity of new commercial assays. The 50-copy cut-off for virologic failure is, therefore, under debate.

Methods: Treated patients with low-level viremia (persistent viral loads (VL) of 50-1000 copies/mL, group A, N = 16) or a blip (single detectable VL, group B, N = 77) were compared to a control group (consistently suppressed viremia since start therapy (<50 copies/mL), N = 79). Residual viremia (detectable viral RNA <50 copies/ml) in the year preceding the first VL above 50 copies/mL (T0) was determined using Roche Cobas-Amplicor v1.5 or CAP-CTM v2.0. Subsequent virologic failure (2 consecutive VLs>500 or 1 VL>1000 copies/mL that was not followed by a VL<50 copies/mL; median follow up 34 months) was assessed.

Results: Significantly more patients in groups A and B had residual viremia in the year preceding T0 compared to controls (50% and 19% vs 3% respectively; p<0.001). Residual viremia was associated with development of low-level viremia or blips (OR 10.9 (95% CI 2.9-40.6)). Subsequent virologic failure was seen more often in group A (3/16) and B (2/77) than in the control group (0/79).

Conclusion: Residual viremia is associated with development of blips and low-level viremia. Virologic failure occurred more often in patients with low-level viremia. These results suggest that low-level viremia results from viral production/replication rather than only assay variation.

Figure 1. Methods.

A  =  patients with low-level viremia; B  =  patients with a single viral blip; C  =  patients with continuously suppressed viremia; T0 =  first detectable viral load for patients of group A and B. Analysis of viral loads in year preceding T0 to determine level of residual viremia. Follow up to determine rate of subsequent virologic failure.

Figure 2. Longitudinal analysis of viral load results in preceding year.

Low-level viremia is often preceded by positive VL results; in 50% of these patients HIV-1 RNA was detected in all VL determinations in the preceding year, compared to only 3% of patients with a sustained suppressed VL (p<.0001).

Figure 3. Kaplan-Meier plot of time to virologic failure (VL>1000 cp/mL) and of time to detectable viremia (≥50 cp/mL).

Figure 4. Levels of immune activation markers at T0.

Lines indicate mean values. No significant difference in levels of soluble CD14 among the groups (p 0.489). There is a trend towards higher levels of CXCL9 in patients with low-level viremia and viral blips than in patients with continuously suppressed viremia (p 0.098).