Serrano-Villar S, Martínez-Sanz J, Ron R, et al. - People with heightened immunosenescence and increased risk of mortality could be identified with a low CD4/CD8 ratio during antiretroviral therapy (ART). Researchers here examined how integrase strand transfer inhibitor (INSTI)-based, protease inhibitor-based, or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART affects long-term CD4/CD8 ratio recovery. In this prospective cohort study, they performed recruitment of 13,026 individuals with HIV registered in the Spanish HIV Research Network (CoRIS) cohort from 45 Spanish hospitals. They analyzed 6,804 individuals contributing 37,149 persons-years and 37,680 observations; median follow-up of 49 months (IQR 22–89) was done. Outcomes revealed greater CD4/CD8 gain in correlation with INSTI-based ART (change per year compared with INSTI was coefficient −0·07 for NNRTI and was −0·08 for protease inhibitors). They observed differences from the first year of therapy and these differences were driven by changes in both CD4 and CD8 cell counts. New evidence was gained in this study reinforcing the positioning of INSTI-based therapies as a first choice and underlining the significance of analyzing the influences of therapeutic interventions on biomarkers correlated with morbidity and mortality beyond the plasma HIV RNA and the CD4 cell counts.