Data from 18 cohorts in Europe and North America, contributing to the ART Cohort Collaboration, where analyzed. The objective was to assess the prognostic value of different levels of persistent low level viremia, particularly for clinical outcomes, i.e. virological failure, AIDS event, and death among HIV-infected patients receiving combination antiretroviral therapy. Eligible patients were those who achieved viral load <50 copies/ml within 3-9 months after antiretroviral therapy initiation. Low level viremia 50-199 was defined as two consecutive viral loads between 50 and 199 copies/ml and low level viremia 200-499 as two consecutive viral loads between 50 and 499 copies/ml, for at least one month, with at least one viral load between 200 and 499 copies/ml, after virological suppression. Cox models were used to estimate the association of low level viremia with virological failure (two consecutive viral loads > 500 copies/ml or one viral load >500 copies/ml, followed by a modification of antiretroviral therapy) and AIDS event or death.

Among 17,902 patients, 624 (3.5%) experienced LLV50-199 and 482 (2.7%) LLV200-499. Median follow-up was 2.3 and 3.1 years for virological and clinical outcomes, respectively. There were 1,903 virological failure, 532 AIDS events and 480 deaths. LLV200-499 was strongly associated with virological failure (adjusted hazard ratio = 3.97, 95% confidence interval = 3.05-5.17). LLV50-199 was weakly associated with virological failure (aHR = 1.38, 95% CI = 0.96-2.00). LLV50-199 and LLV200-499 were not associated with AIDS event or death (aHR = 1.19, 95% CI = 0.78-1.82; and aHR = 1.11, 95% CI = 0.72-1.71, respectively).

In conclusion, LLV200-499 was strongly associated with virological failure, but not with AIDS event or death. LLV50-199 was not associated with virological nor clinical outcomes. These results support the definition of virological failure as a confirmed viral load >200 copies/ml.