Soluble CD14 and IL-12p70 on early antiretroviral therapy predict HIV load setpoint after treatment interruption

Abstract

Objective: After analytical treatment interruption (ATI), viral rebound occurs in most people with HIV. The time to viral rebound (TTVR) is likely determined by the properties of the viral reservoir as well as the antiviral immune response. Soluble biomarkers of immune activation may be predictive of TTVR and plasma viral load (pVL) setpoint after ATI. The objective of this study is to identify these soluble biomarkers. Design: A retrospective biomarker analysis of the Primo-SHM trial who were treated 24 or 60 weeks during early HIV infection. Methods: Thirty-five biomarkers were measured at ATI in 65 participants. Association between biomarkers and reservoir size, TTVR and pVL at setpoint was assessed. Results: SCD14 correlated to pVL setpoint (B ¼ 0.598; P ¼ 0.004) and lower levels of IL-12p70 to a higher level of pVL setpoint (B ¼ -0.448; P ¼ 0.04). SCD163 correlated to levels of total HIV-DNA (B ¼ 0.413; P ¼ 0.007). Conclusion: An increased pVL setpoint was associated with higher sCD14 and lower IL-12p70 at ATI, and increased total HIV-DNA was associated with higher sCD163 at ATI. SCD14 and sCD163 are biomarkers of monocyte activation, whereas IL-12p70, produced by monocytes, is essential for inducing Th1 responses. This underscores the relation between immune activation and diminished immune control of HIV. Our findings indicate that sCD14 and IL-12p70 could serve as predictive biomarkers for favorable outcomes in cure interventions.