CROI 2020 Abstract eBook
Background: There are limited data on the clinical implications of persistent chronic immune dysregulation in HIV-1-infected African populations on suppressive antiretroviral therapy (ART). We investigated the prognostic value of elevated plasma immune biomarkers, during suppressive ART, in predicting impaired CD4 T-cell recovery and virological rebound during 6 years of follow- up. Methods: In a multi-country African adult cohort, we measured 8 selected systemic biomarkers (IL-6, IP-10/CXCL10, MCP-1/CCL2, MIG/CXCL9, LBP, CRP, sCD163, and sCD14) in 398 participants with suppressed plasma HIV-RNA (<50 cps/mL) after 12 months of non-nucleoside reverse-transcriptase inhibitor-based ART. We estimated associations between each of the month-12 biomarkers and 2 long-term outcomes: 1) CD4 T-cell recovery, using a multivariable linear mixed model; and 2) virological rebound (defined as single HIV-RNA>1000 cps/mL), using multivariable interval-censored survival analysis. Results: 229 participants (58%) were female, median age was 37 years (IQR 33-43), and country of origin was Kenya (n=92), Nigeria (n=57), South Africa (n=65), Uganda (n=121) and Zambia (n=63). Median CD4 T-cell count rose from 291 cells/µL (IQR 216-395) at month 12 to 458 cells/µL (IQR 340-602) at month 72. Participants with elevated levels of sCD14 (coefficient -83.38, 95%CI -163.49 to -3.27; p=0.041), IP-10 (-46.79, 95%CI -95.05 to 1.47; p=0.057), MIG (-34.78, 95%CI -67.27 to -2.29; p=0.036), and CRP (-28.49, 95%CI -45.95 to -11.04; p=0.001) were more likely to experience impaired CD4 T-cell recovery. Frommonth 12 after ART initiation onwards, we recorded 1148 person-years of follow-up, with 47 events of virological rebound (incidence rate of 40.9, 95%CI 30.8-54.5, per 1000 person-years). Risk of virological rebound was increased for participants with an elevated IP-10 level (hazard ratio [HR] 1.81 per log 10 pg/ mL unit increase, 95%CI 1.03-3.18; p=0.038), and reduced for those with an elevated MCP-1 level (HR 0.25 per log 10 pg/mL unit increase, 95%CI 0.07-0.87; p=0.030). None of the other biomarkers were significantly associated (figure). Conclusion: Persistent systemic inflammation and immune activation during suppressive ART was associated with impaired long-term CD4 T-cell recovery and virological rebound; the counterintuitive MCP-1 association requires further investigation. Further research needs to explore the potential for adjunct therapies targeting relevant inflammatory pathways.
Background: We aimed to identify an HIV-related microbiota signature, independent of sexual preferences and demographic confounders, to assess a possible impact of the microbiome on metabolic comorbidities. Methods: 405 HIV-infected and 111 uninfected individuals, stratified to sexual behaviour (men who have sex with men, MSM and non-MSM), were included from the COCOMO study. Stool samples were analyzed using 16S rRNA sequencing. Hypotheses were tested using regression models adjusting for known confounders. Results: Microbiota alterations in HIV-positive MSM and uninfected MSM were largely overlapping. After filtering out MSM-associated microbiota traits and adjusting for relevant confounders, we identified an HIV-related dysbiosis, consisting of lower biodiversity, increased relative abundance of Gammaproteobacteria and Desulfovibrionaceae and decrease in several Clostridia (Figure 1). HIV-related dysbiosis was associated with previous immunodeficiency (low nadir CD4), elevated microbial translocation markers (soluble CD14 and LPS-binding protein, p<0.05), and a 2-fold (adjusted Odds Ratio (aOR) 1.97 [1.12; 3.46]) increased excess risk of metabolic syndrome, the latter driven by increase in Desulfovibrionaceae and decrease in several Clostridia of the Lachnospiraceae and Ruminococcaceae families (Butyrivibrio, Coprococcus-2, Lachnospiraceae UCG-001 and CAG-56). In individuals with a history of AIDS, this microbiota profile was associated with 8-fold (aOR 8.14 [1.74; 38.07]) excess risk of metabolic syndrome and 6-fold (aOR 6.71 [1.35; 33.50]) excess risk of abdominal obesity. Conclusion: HIV infection was associated with altered bacterial composition, independently of sexual behaviour and demographic factors. HIV-related dysbiosis was associated with increased risk of metabolic syndrome, particularly in individuals with previous severe immunodeficiency. The excess metabolic risk was driven by increased Desulfovibrionaceae, H2S-producing bacteria with toxic effects on the gut epithelium, and decrease of potentially butyrate- producing Clostridia. As outgrowth of Desulfovibrio and reduction in Clostridia have been shown to trigger metabolic alterations in immunodeficient mice, our findings suggest a potential interplay between HIV-related dysbiosis, previous immunodeficiency and future risk of metabolic comorbidities.
224 ALTERED GUT MICROBIOTA AND HOST LIPID METABOLITE PROFILES IN HIV INFECTION Zheng Wang 1 , Mykhaylo Usyk 1 , Yunping Qiu 1 , Simin Hua 1 , Tao Wang 1 , Xiaonan Xue 1 , Irwin J. Kurland 1 , Alan Landay 2 , Kathryn Anastos 1 , Robert C. Kaplan 1 , Robert Burk 1 , Qibin Qi 1 1 Albert Einstein College of Medicine, Bronx, NY, USA, 2 Rush University Medical Center, Chicago, IL, USA Alterations in gut microbiota (GMB) and host blood metabolite profiles have been noted in people living with HIV (PWV). However, it remains unclear
223 HIV-RELATED MICROBIOME, PREVIOUS IMMUNODEFICIENCY, AND EXCESS METABOLIC RISK Marco Gelpi 1 , Beate Vestad 2 , Simen H. Hansen 3 , Kristian Holm 3 , Ninna Drivsholm 1 , Alexandra Goetz 3 , Hedda Hoel 2 , Nikolai Kirkby 1 , Birgitte Lindegaard 1 , Anne-Mette Lebech 4 , Jan Gerstoft 1 , Jens D. Lundgren 1 , Johannes R. Hov 3 , Susanne D. Nielsen 1 , Marius Troseid 2 1 Rigshospitalet, Copenhagen, Denmark, 2 Oslo University Hospital, Oslo, Norway, 3 University of Oslo, Oslo, Norway, 4 Hvidovre Hospital, Hvidovre, Denmark
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