Impact of low-level viremia on clinical and virological outcomes in treated HIV-1-infected patients.

BACKGROUND The goal of antiretroviral therapy (ART) is to reduce HIV-related morbidity and mortality by suppressing HIV replication. The prognostic value of persistent low-level viremia (LLV), particularly for clinical outcomes, is unknown. OBJECTIVE Assess the association of different levels of LLV with virological failure, AIDS event, and death among HIV-infected patients receiving combination ART. METHODS We analyzed data from 18 cohorts in Europe and North America, contributing to the ART Cohort Collaboration. Eligible patients achieved viral load below 50  copies/ml within 3-9 months after ART initiation. LLV50-199 was defined as two consecutive viral loads between 50 and 199  copies/ml and LLV200-499 as two consecutive viral loads between 50 and 499  copies/ml, with at least one between 200 and 499  copies/ml. We used Cox models to estimate the association of LLV with virological failure (two consecutive viral loads at least 500  copies/ml or one viral load at least 500 copies/ml, followed by a modification of ART) and AIDS event/death. RESULTS 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 1903 virological failure, 532 AIDS events and 480 deaths. LLV200-499 was strongly associated with virological failure [adjusted hazard ratio (aHR) 3.97, 95% confidence interval (CI) 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/death (aHR 1.13, 95% CI 0.81-1.68; and aHR 0.95, 95% CI 0.62-1.48, [corrected] respectively). CONCLUSION LLV200-499 was strongly associated with virological failure, but not with AIDS event/death. Our results support the US guidelines, which define virological failure as a confirmed viral load above 200  copies/ml.