The natural history and clinical significance of intermittent viraemia in patients with initial viral suppression to < 400 copies/ml

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Abstract
To determine the prevalence and prognostic significance of intermittent viraemia (IV) in patients who attained an undetectable viral load (VL) < 400 copies/ml within 6 months on highly active antiretroviral therapy (HAART). Retrospective analysis of viral load rebound ≥ 400 copies/ml and CD4 cell counts rise for 765 patients followed for ≥ 12 months following initial VL undetectability, comparing the 226 (29.5%) who maintained an undetectable VL for > 1 year from initiation of HAART and 122 (15.9%) who had one or more episodes of IV. Genotypic resistance was evaluated at the time of the first episode of IV ≥ 2000 copies/ml. Patients with IV had a threefold higher rate of sustained virological rebound [hazards ratio (HR), 3.15; 95% confidence interval (CI), 1.72–5.77;P < 0.001). For patients with and without IV, the Kaplan–Meier estimates at 24 and 36 months after initiation of HAART were 19.3% (95% CI, 8.9–21.5) versus 7.7% (95% CI, 4.5–13.0) and 31.6% (95% CI, 21.8–44.2) versus 12.9% (95% CI, 7.5–21.5), respectively (P < 0.001). The median CD4 cell count rise at 18 and 24 months was significantly lower in those with IV than in those without: 138 [interquartile range (IQR), 58–221] versus 224 × 106 cells/l (IQR, 119–357) (P = 0.0001) and 200 (IQR, 89–294) versus 260 × 106 cells/l (IQR, 125–384) (P = 0.003), respectively. In a subgroup of 16 patients, genotypic resistance mutations were found in the reverse transcriptase gene for five (31%) and in the protease gene in one. A probable contributing factor/event was identified for most patients with IV, such as poor adherence (42.6%), intercurrent infection (26.2%) or drug interaction (6.8%). Patients with IV > 400 copies/ml are three times more likely to experience sustained viral rebound and to have an impaired CD4 cell rise relative to those who maintain undetectable VL. This supports the adoption of a more pro-active approach to treatment intensification and the need for caution with structured treatment interruptions.

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