CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

positively associated with HIV DNA at yr1 (Spearman r= 0.24 and 0.27, p≤0.019) and yr4 (r= 0.31 and 0.36, p≤0.002), but not associated at pre-ART. HIV Ab measurements were not associated with cell-associated HIV RNA (CA-RNA) at pre-ART, yr1 or yr4. There was a marginal positive association between S/Co and the AI slope/yr from yr1 to yr4 with total HIV DNA at yr4 (r= 0.21 and 0.20, p≤0.05). Conclusion: The correlations found between Ab and HIV DNA levels suggest that host immune responses may be used to estimate the frequency of HIV-infected cells in patients on suppressive ART. The finding that Ab assay results do not correlate with CA-RNA levels suggests that most CA-RNA does not result in production or presentation of viral proteins. Whether Ab measures correlate with cellular HIV antigen expression will be important to determine.

280 PERSISTENT IMMUNE ACTIVATION DESPITE ART: THE “DIE IS CAST” BEFORE ART INITIATION

Rajesh T. Gandhi 1 , Deborah McMahon 2 , Ronald Bosch 3 , Christina Lalama 3 , Bernard Macatangay 2 , Joshua Cyktor 2 , Ann Collier 4 , Charles Rinaldo 2 , Joseph J. Eron 5 , John Mellors 2 1 Massachusetts General Hosp and Ragon Inst, Boston, MA, USA, 2 Univ of Pittsburgh, Pittsburgh, PA, USA, 3 Harvard Univ, Boston, MA, USA, 4 Univ of Washington, Seattle, WA, USA, 5 Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: The relationships among pre-ART and on-ART levels of HIV, immune activation and inflammation are incompletely understood, in part because prior studies have been small or cross-sectional. Methods: We measured HIV DNA, cell associated HIV RNA (CA-RNA), inflammatory biomarkers (IL-6, sCD14, hsCRP, sCD163), T cell activation (% CD38+/HLA-DR+) and cycling (%Ki67+) in 101 participants who initiated ART during chronic infection and had well-documented sustained suppression of plasma viremia for a median of 7 yrs (ACTG A5321). Assays were performed on samples from pre-ART and from on-ART yrs 1, 4 and yrs 6-15. Results: Following ART initiation, HIV DNA, CA-RNA, IL-6, sCD163, T cell activation and T cell cycling declined significantly. Higher pre-ART levels of HIV DNA and CA-RNA were associated with higher on-ART levels of HIV DNA and CA-RNA at all time points (Table). Pre-ART levels of IL-6, sCD163, sCD14 and hsCRP were also significantly correlated with on-ART levels of the same biomarkers at yrs 1, 4 and 6-15 of ART, even after adjusting for pre-ART plasma HIV RNA and CD4 count. Pre-ART CD4 cell activation was directly associated with on-ART CD4 cell activation at yr 1 (r= 0.45, p<0.001) and yr 4 (r= 0.23, p=0.02), although correlations between pre-ART and on-ART T cell activation diminished over time on treatment. By contrast, pre-ART T cell cycling levels correlated with on-ART levels at all time points. Markers of inflammation and T cell activation were associated with plasma HIV RNA levels before ART was initiated (e.g. CD4 activation and plasma HIV RNA, r=0.41, p<0.001) but there were no consistent associations between these markers and HIV DNA or CA-RNA during long-term ART (e.g., CD4 activation and HIV DNA at yr 4 (n=96): r=0.10, p=0.31; at yrs 6-15 (n=62): r=−0.06, p=0.65). Conclusion: Higher levels of inflammation and activation before ART were associated with higher levels during ART, indicating that immunologic events that occurred well before ART initiation had long-lasting effects despite sustained virologic suppression (i.e., “the die is cast” before ART initiation). We did not find evidence for HIV persistence driving or being driven by inflammation or activation during ART. These findings should stimulate studies of viral and host factors that affect immunologic, inflammatory and virologic set points prior to ART initiation and should inform the design of strategies to reduce HIV reservoirs and dampen inflammation and activation that persist despite ART.

Poster and Themed Discussion Abstracts

CROI 2017 110