Persistent low-level viraemia and virological failure in HIV-1-infected patients treated with highly active antiretroviral therapy

Abstract

Objective: To assess the prognostic significance of persistent low-level viraemia (PLV, defined as persistent plasma viral loads of 51-1000 HIV-1 RNA copies/mL for at least 3 months) in patients who had achieved viral suppression on antiretroviral therapy (ART).

Methods: A retrospective cohort of HIV-infected patients who received ART, were followed-up for > or =12 months, made regular visits to the clinic during which blood tests were performed for an ultrasensitive HIV RNA assay every 3 months, and achieved viral loads <50 copies/mL were evaluated. Virological failure was defined as two consecutive viral load measurements >1000 copies/mL.

Results: Of 362 patients, 78 (27.5%) experienced PLV. The demographics of patients with and without PLV were similar. PLV occurred at a mean (+/-standard deviation) of 22.6+/-16.9 months after ART initiation and lasted for 6.4+/-3.4 months. During a median follow-up of 29.5 months, patients with PLV had a higher rate of virological failure (39.7% vs 9.2%; P < 0.001). The median time to failure was 68.4 months [95% confidence interval (CI) 37.0-99.7] for patients with PLV and >72 months for patients without PLV (log rank test, P < 0.001). By Cox regression, patients with PLV had a greater risk of virological failure [hazard ratio (HR) 3.8; 95% CI 2.2-6.4; P < 0.001]. Among patients with PLV, a PLV of >400 copies/mL (HR 3.3; 95% CI 1.5-7.1; P = 0.003) and a history of ART (HR 2.4; 95% CI 1.0-5.7; P = 0.042) predicted virological failure.

Conclusions: PLV is associated with virological failure. Patients with a PLV >400 copies/mL and a history of ART experience are more likely to experience virological failure. Patients with PLV should be considered for treatment optimization and interventional studies.