CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

406 A RANDOMIZED TRIAL OF ADJUNCTIVE TELMISARTAN TO REDUCE CNS INFLAMMATION IN ACUTE HIV Michael J. Peluso 1 , Eugène Kroon 2 , Phillip Chan 2 , Somporn Tipsuk 2 , Carlo Sacdalan 2 , Jennifer Chiarella 3 , Magnus Gisslén 4 , Henrik Zetterberg 4 , Rob Gorelick 5 , Duanghathai Suttichom 2 , Napapon Sailasuta 6 , Robert Paul 7 , Jintanat Ananworanich 8 , Serena S. Spudich 3 , for the RV408/SEARCH 018 Study Team 1 University of California San Francisco, San Francisco, CA, USA, 2 Thai Red Cross AIDS Research Center, Bangkok, Thailand, 3 Yale University, New Haven, CT, USA, 4 University of Gothenburg, Gothenburg, Sweden, 5 National Cancer Institute, Frederick, MD, USA, 6 University of Hawaii, Honolulu, HI, USA, 7 University of Missouri St Louis, St Louis, MO, USA, 8 US Military HIV Research Program, Silver Spring, MD, USA Background: Telmisartan is an angiotensin II receptor antagonist that inhibits inflammatory cytokines and macrophage activity. We hypothesized that initiation of antiretroviral therapy (ART) with adjunctive telmisartan in acute HIV infection (AHI) would reduce inflammation and immune activation and alter the pathogenesis of HIV within the central nervous system (CNS). Methods: 21 participants with AHI were randomized 2:1 to initiate treatment with ART +/- telmisartan; after 48 weeks, all individuals received ART alone. At baseline, 48, and 72 weeks, we measured blood and cerebrospinal fluid (CSF) biomarkers of HIV infection, inflammation, and neuronal injury. Brain magnetic resonance spectroscopy (MRS) metabolites and neuropsychological (NP) performance assessed by a battery of 16 tests (summarized as NPZ) were evaluated at baseline and weeks 48 and 72. Wilcoxon rank sum and Mann Whitney tests examined differences within individuals and between groups at each time point. Results: All participants were Thai men who have sex with men. At enrollment, median age was 29 years (IQR 24-34), CD4+ T cell count 479 (95-688), and estimated duration of infection 16 days (13-22). Pre-ART median log plasma and CSF HIV RNA levels were 5.95 (5.36-6.48) copies/mL and 2.82 (2.17-4.36) copies/mL. Plasma and CSF HIV RNA using highly sensitive assays (lower limit of quantitation of 0.3 copies/mL) did not differ between groups at 48 or 72 weeks. While levels of CSF inflammatory biomarkers declined in both arms, there were no significant differences between arms in levels of CSF neopterin, IP-10, sCD14, MCP-1, sCD163, neurofilament light chain or YKL-40 at 48 or 72 weeks. MRS metabolites in basal ganglia and white matter remained stable over time in both arms and there were no significant differences between arms at 48 or 72 weeks. Individuals on telmisartan had higher (better) overall NPZ scores at 48 weeks (0.64 vs 0.05; p=0.04) and 72 weeks (0.70 vs 0.08; p=0.06), although this difference appeared to be driven by a subsample in the telmisartan group (n=3) who exhibited significant improvement from baseline. Conclusion: In this pilot study of telmisartan as an adjunct to ART during AHI, telmisartan did not affect CNS biomarkers of inflammation or injury. The association with NP performance warrants further investigation.

Poster Abstracts

407 INFLAMMATORY MARKERS SHOW DYNAMIC CHANGES IN ACUTE HIV AND PREDICT COGNITIVE OUTCOMES August A. Longino 1 , Javier R. Lama 2 , Peter Brandes 2 , Eduardo Ruiz 2 , Cecilia Correa 2 , Serena S. Spudich 3 , Christopher D. Pilcher 4 , Kevin Robertson 5 , Rachel A. Bender Ignacio 6 , Ann Duerr 6 1 University of Washington, Seattle, WA, USA, 2 Asociacion Civil Impacta Salud y Educacion, Lima, Peru, Yale University, New Haven, CT, USA, 4 University of California San Francisco, San Francisco, CA, USA, 5 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 6 Fred Hutchinson Cancer Research Center, Seattle, WA, USA Background: HIV-associated neurocognitive disorder (HAND) has been associated with elevated inflammatory markers in the peripheral blood and cerebrospinal fluid (CSF) in chronic HIV. We investigated the dynamics of viral load and inflammatory markers in CSF and plasma during acute HIV infection and their impact on longitudinal neurocognitive performance (NP) after antiretroviral therapy (ART) in Peru. Methods: MSM and transgender women in the Sabes study were followed with monthly testing (HIV Ab & RNA) and enrolled within 3 months of HIV acquisition. In ART-naïve HIV+ participants, 39 inflammatory markers were measured in plasma (N = 87) and 37 in CSF (N = 29) at enrollment. Time from infection to enrollment (ITE) was estimated by an algorithm using testing history (type, date and result of test). NP was assessed with a 15-test battery, averaged as a total Z score derived from Peruvian normative data and administered every 24 weeks. Linear regression was used to evaluate associations between VL, biomarkers, and ITE. In a subset analysis of 42 participants who started ART at enrollment, 13 of whom provided CSF samples, biomarker levels were used as predictors of change in standardized NP score from baseline ( Δ NP). We adjusted for multiple comparisons with the Benjamini-Hochberg (BH) method. Results: Longer ITE was associated with lower VL in CSF (β = -0.024 log 10 copies/mm 3 /day, p = 0.03) and plasma, (β = -0.037 log 10 copies/mm 3 /day, p = <0.0001). In univariate analysis, longer ITE was associated with lower levels of 24 and higher levels of 4 biomarkers. After adjustment with BH, ITE was negatively associated with baseline levels of VCAM-1, and IFN-y in both plasma and CSF, negatively associated with CSF CD-163 and positively associated with plasma CD-163. In the unadjusted subset analysis, higher levels of the following biomarkers predicted a negative β NP at α 2 time points: plasma YKL40; plasma and CSF IL-16, plasma IL-6, CSF TNF-β, CSF IL-16, CSF TNF- α, and CSF IP-10. Conclusion: Higher baseline values of key inflammatory biomarkers in plasma and CSF in early HIV were correlated with greater reductions in NP score over time after ART. There was also a novel pattern of CSF and plasma inflammatory marker dynamics observed in the first two months of untreated HIV infection.

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