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


METHODS
Retrospective analysis of viral load rebound > or = 400 copies/ml and CD4 cell counts rise for 765 patients followed for > or = 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 > or = 2000 copies/ml.


RESULTS
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 x 10(6) cells/l (IQR, 119-357) (P = 0.0001) and 200 (IQR, 89-294) versus 260 x 10(6) 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%).


CONCLUSIONS
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.
Easterbrook
Philippa J
PJ
Department of HIV/GUM, Guy's, King's and St Thomas' School of Medicine, King's College Hospital, London, UK.
Ives
Natalie
N
Waters
Anele
A
Mullen
Jane
J
O'Shea
Siobhan
S
Peters
Barry
B
Gazzard
Brian G
BG
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D006801:Humans; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy* / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors