Persistent Low-Level Viremia is an Independent Risk Factor for Virologic Failure: A Retrospective Cohort Study in China

Qun Li,1,2,* Meiling Chen,2,3 Hongxin Zhao,1,2 Fengting Yu,2,4 Liting Yan,1,2 Jiang Xiao,1,2 Guiju Gao,1,2 Di Yang,1,2 Fujie Zhang1,2,* 1Department of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Clinical Center for HIV/AIDS, Capital Medical University, Beijing, People’s Republic of China; 3The Medical Statistic Department, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Laboratory of Infectious Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fujie ZhangClinical and Research Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of ChinaTel +86 10 84322581Email treatment@chinaaids.cnBackground: Whether intermittent low-level viremia (iLLV/blip) or persistent low-level viremia (pLLV) increases the risk of virologic failure (VF) in HIV-1 patients is controversial. The objective of this study was to investigate the incidence of blip/pLLV and the association between blip/pLLV and VF in a Chinese antiretroviral therapy cohort.Methods: HIV-1 patients who underwent antiretroviral therapy (ART) from 2005 to 2018 and had at least two viral load (VL) measurements after a minimum of 6 months ART treatment were included. VF was defined as one or more VL measurements of ≥ 1000 copies/mL. Blip was described as an isolated VL measurement between 50 and 999 copies/mL, and pLLV was defined as two or more consecutive VL measurements between 50 and 999 copies/mL. Blip and pLLV were categorized separately into three groups: 50– 200, 201– 400 and 401– 999 copies/mL. The Cox proportional hazard model was used to explore the association between blip/pLLV and VF.Results: In total, 8098 participants were enrolled in this long-term cohort study. A 94.3% of the participants were male and among which 77.3% were infected through homosexual transmission. Blip occurred in 4.0% (325/8098) of the patients with an incidence of 0.73 per 100 person-years (/100 PYS) of follow-up (95% CI: 0.71– 0.76), whereas pLLV occurred in 1.3% of the patients (102/8098) with an incidence of 0.23/100 PYS of follow-up (95% CI: 0.21– 0.25). All the three categories of pLLV were associated with VF: pLLV 50– 200 [aHR: 3.82 (1.95– 7.47)], pLLV 201– 400 [aHR: 5.36 (2.35– 12.22)] and pLLV 401– 999 [aHR: 13.51 (8.28– 22.02)]. However, blip is not significantly associated with VF in any category.Conclusion: Our study suggested that patients with pLLV had an increased risk of subsequent VF. Therefore, if pLLV occurs in patients, monitoring and corresponding measurements must be strengthened to avoid the subsequent VF.Keywords: HIV-1, blip, persistent low-level viremia, virologic failur