Title

Incomplete ART adherence is associated with higher interleukin-6 in individuals with HIV who achieved virologic suppression in the immediate arm of the Strategic Timing of Antiretroviral Treatment (START) study

Presenter

Jose Castillo-Mancilla

Authors

J. Castillo-Mancilla¹, A.N. Phillips², J.D. Neaton³, J. Neuhaus³, S. Sharma³, J.V. Baker³, S. Collins⁴, S. Mannheimer⁵, S. Pett^2,6, V. Touzeau-Römer⁷, M.N. Polizzotto⁶, J.D. Lundgren⁸, E.M. Gardner⁹, INSIGHT START Study Group

Institutions

¹University of Colorado-Anschutz Medical Campus, Division of Infectious Diseases, Aurora, United States, ²University College London, London, United Kingdom, ³University of Minnesota, Minneapolis, United States, ⁴HIV i-Base, London, United Kingdom, ⁵Columbia University, New York, United States, ⁶Kirby Institute/University of New South Wales, Sydney, Australia, ⁷University of Vienna, AKH, Vienna, Austria, ⁸CHIP Rigshospitalet, Copenhagen, Denmark, ⁹Denver Health Medical Center, Denver, United States

Background: Heightened inflammation is predictive of serious non-AIDS events in treated HIV infection. Recently, incomplete ART adherence has been associated with chronic residual inflammation, even in the setting of viral suppression. Herein, we evaluated whether this association is also observed in individuals who started ART with higher CD4⁺ T-cell counts (>500 cells/mm³) and achieved virologic suppression in the immediate arm of the START study.
Methods: Plasma levels of interleukin-6 (IL-6), D-dimer and C-reactive protein (CRP) were analyzed both at baseline and 8 months after ART initiation in treatment-naïve individuals with HIV enrolled in the immediate arm of START. Adherence was assessed by self-report and was determined to be incomplete if a participant reported not taking “all of my pills” in the preceding 7-days for any ART medication. Multivariable linear regression models were utilized to analyze the association between ART adherence and each biomarker at the 8-month visit (on a ln scale) in participants who achieved virologic suppression (< 50 copies/mL). Data are presented as fold differences in biomarker concentrations in individuals who reported incomplete vs. 100% adherence at the 8-month visit.
Results: Of the 2,325 participants in the immediate ART arm, a total of 1,627 participants (422 female, 718 White, 479 Black, 215 Hispanic, 149 Asian) who had virologic suppression (< 50 copies/mL), adherence data and biomarker concentrations on the same day at the 8-month visit were included in the analysis. The median age was 36 (IQR 29-44) years. Median CD4⁺ T-cell count and HIV viral load before ART initiation were 651 (IQR 585, 769) cells/mm³ and 13,123 (IQR 3,331, 42,169) copies/mL, respectively. Incomplete adherence was reported in 109 (7%) participants. Higher plasma concentrations of IL-6 were observed in participants who reported incomplete adherence in comparison with those who reported 100% adherence (Table).

Adjusted^a fold difference in plasma concentrations of biomarkers of inflammation and coagulopathy in participants who achieved viral suppression (<50 copies/mL) and reported incomplete ART adherence after 8 months of therapy in the immediate arm of START.
Biomarker	Number of participants	Fold higher level vs. 100% adherence^b	95% CI	P-value
IL-6 (pg/mL)	1,627	1.14	(1.01 - 1.28)	0.03
D-dimer (μg/mL)	1,622	0.97	(0.88 - 1.07)	0.55
CRP (mg/L)	1,627	1.25	(1.00 - 1.57)	0.05
^aModels were adjusted for age, race, level of education, region, HIV risk group, hepatitis B or C co-infection and baseline levels of biomarkers.^b100% adherence was defined as reporting taking “all of my pills” for all ART medication doses in the preceding 7-day period.

[Table]

Conclusions: Incomplete self-reported ART adherence was associated with higher concentrations of IL-6 in individuals with CD4⁺ T-cell >500 cells/mm³who achieved virologic suppression by conventional assays early after initiation of therapy. These findings are similar to previous observations and emphasize the need to aim for the highest possible level of adherence to maximize the biological benefit of ART.

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