Understanding viral blips in people with HIV on antiretroviral therapy: a nationwide Swedish cohort study of 4,210 individuals

Background The pathogenesis and clinical consequences of viral blips are not completely understood. The aim of this large nationwide study was to investigate the incidence of viral blips and factors associated with them, with particular attention to the third (core) agent class—comparing integrase strand transfer inhibitor (INSTI)-based regimens with non-nucleoside reverse transcriptase inhibitor (NNRTI)- and protease inhibitor (PI)-based regimens. Methods From the Swedish national InfCareHIV cohort, we included treatment-naïve adults who commenced antiretroviral therapy (ART) from 1 January 2007; data were extracted on 30 September 2020. Viral blips were defined as transient plasma HIV RNA levels between 50 and 500 copies/mL preceded and followed by HIV RNA < 50 copies/mL. Virological failure was defined as two consecutive HIV RNA samples > 200 copies/mL or a single sample of HIV RNA > 1,000 copies/mL, in previously suppressed individuals with more than 12 months since ART initiation. Cox regression was used for event analyses. Results In total, 4,210 individuals were included, of whom 853 (20.3%) had 1—6 registered blips. Median observation time was 5.5 years (range 0.5—13.7). Blip incidence was 4.35 (95% CI 4.02—4.69) per 100 person-years. In a sensitivity analysis applying the narrower definition of 50—199 copies/mL, the incidence was 3.80 (95% CI 3.49—4.11) per 100 person-years. Individuals on INSTIs and NNRTIs had similar risk, while those on PIs had a significantly higher risk of blips (hazard ratio [HR] 1.22, 95% CI 1.03—1.45; p = 0.02). Transient viremia was not associated with an increased risk of subsequent virological failure; individuals with blips had a lower risk than those with continuously undetectable HIV RNA (HR 0.54, 95% CI 0.41—0.71; p < 0.0001). Conclusion Individuals on INSTI- and NNRTI-based ART had fewer viral blips than those on PI-based ART. In this cohort, transient viremia below 500 HIV RNA copies/mL was not associated with a higher risk of subsequent virological failure. Clinical trial number Not applicable.