LIVE OF THE CROI 2018: TUESDAY, MARCH 6, 2018
Christina Psomas, MD, PhD is our “grand reporter”
Nichole Klatt (University of Washington, Seattle, WA, USA) was the first speaker of the Tuesday Plenary Session (PL-2) describing how microbial dysbiosis can be associated with many diseases (Abstract 64). Healthy vaginal microbiome per se is lactobacillus dominant, loss of Lactobacillus spp, increased anaerobic bacteria and higher diversity of vaginal microbiome defines vaginal microbiome dysbiosis. Clinical bacterial vaginosis testing by Nugent score does not accurately predict vaginal dysbiosis. Vaginal microbial dysbiosis has been associated with clinical vaginosis, inflammation, reduced epithelial barrier integrity and increased HIV infection risk. Effectiveness of PrEP and varying outcomes in women that have been attributed to adherence may also have biological explanations, namely direct metabolism of topical antiretroviral-based PrEP (TFV-DP, dapivirine) by dysbiotic bacteria and enhanced HIV infection in the presence of dysbiotic bacteria. In contrast, Bacteria do not metabolize Tenofovir Alafenamide (TAF), which is a very promising result for a more efficacious PrEP.
Robert H. Remien (HIV Center for Clinical & Behavioral Studies, NYS Psychiatric Institute and Columbia University, New York, NY, USA) addressed Mental Health as a crucial component to ending the HIV epidemic (Abstract 65). Mental health problems including substance abuse are one of the most significant areas of co-morbidity for people living with HIV/AIDS (PLWHA) worldwide and are more prevalent among PLWHA (estimated 50%) than the general population. HIV effects on the brain contribute to neuro-cognitive disorders as well as disturbed affect regulation among PLWHA, and the chronic inflammatory response to HIV infection is hypothesized to contribute to elevated rates of mental health problems among PLWHA. A range of psychological interventions have been shown to improve mental health among PLWHA, including reducing depression and anxiety and increasing quality of life and psychological well- being. Further, treatment for mental disorders and behavioral (i.e., adherence) interventions has an additive effect, positively affecting HIV health outcomes along the HIV prevention and treatment continua. We will not be able to achieve “ending the epidemic” (EtE) goals, if we do not address mental health co-morbidities among our most vulnerable populations.
Jason V. Baker (HCMC / University of Minnesota, Minneapolis, MN, USA) opened the Oral Abstract O-06 Non-AIDS Complications Session presenting the immunologic and inflammatory analysis on behalf of the INSIGHT START Study Group (abstract 74). In this analysis, they compared early measures of immunologic and inflammatory biomarkers for their ability to predict prognosis and/or explain the treatment effect. Analyses included 4273 (92%) START participants with IL-6, D-dimer and CD4 counts at baseline. 129 participants had primary events (57 AIDS, 72 Serious Non-AIDS events or non-AIDS deaths). In this START population, levels (assessed at baseline and month 8) of D-dimer, IL-6, CD8, and CD4:CD8, but not CD4, demonstrated strong associations with subsequent risk of AIDS and SNA. D-dimer, IL-6, CD8, and CD4:CD8 had independent contributions to clinical risk, reflecting distinct pathways.
Lene Ryom (CHIP, Department of Infectious Diseases, Copenhagen, Denmark) presented insights into the prognosis of serious clinical events (SCE) after chronic kidney disease (CKD) in D:A:D participants (abstract 75). 2467 persons with and 33427 persons without CKD were included. During 2.7 (IQR 1.1-5.1) years median follow-up after CKD 595 persons with CKD (24.1%) developed a SCE (IR 68.9/1000PYFU [95%CI 63.4-74.4]) with 7.9% [6.9-9.0] estimated to have a SCE at 1 year, death being the most common SCE (12.7%). In persons without CKD the SCE IR was 23.0/1000PYFU [22.4-23.6] with 2.8% [2.6-3.0] estimated to have a SCE at 1 year. In adjusted models poor HIV control (2.72 [2.01-3.69]), low BMI (1.68 [1.14-2.48]), diabetes (1.60 [1.19-2.15]), smoking (1.48 [1.06-2.07]) and higher eGFR (0.74 [0.68-0.80]) were strongly associated with death; poor HIV control (3.05 [1.87-4.95]), low BMI (1.96 [1.11-3.47]) and smoking (1.75 [1.02-3.00]) with other AIDS; smoking (1.78 [1.07-2.99]) and diabetes (1.65 [1.05- 2.57]) with NADM; dyslipidaemia (2.22 [1.40-3.52]), smoking (1.98 [1.22-3.19]), diabetes (1.81 [1.16-2.81]) and higher eGFR (0.81 [0.72-0.92]) with CVD. These data suggest that persons with CKD have a high SCE burden with almost 1/5 developing SCE within 3 years, requiring close monitoring.
Andreas Dehlbaek Knudsen (Rigshospitalet, University of Copenhagen, Copenhagen, Denmark) described prevalence and risk factors for peripheral artery disease (=PAD) in PLWH compared to uninfected controls by means of ankle-brachial index (Abstract 76). 908 PLWH aged ≥40 were recruited from the Copenhagen comorbidity in HIV infection (COCOMO) study. PAD was detected in 112 PLWH (12% [95% 10-14]) and 623 similarly aged, sex matched uninfected controls (6% [95% 5-6]), (p<0.0001); odds ratio (OR)=2.4 [95% 1.9-2.9], adjusted OR=1.7 [95% 1.3-2.3, p=.0002]. Thus, HIV was independently associated with PAD. Age, female sex, smoking status, hypertension, intermittent claudication, and kidney function were independently associated with risk of PAD, irrespective of HIV status. In PLWH, neither previous AIDS, CD4 nadir, CD4 count, CD4:CD8-ratio, HCV coinfection, cART nor duration of infection were associated with PAD.
Wendy Post (The Johns Hopkins University, Baltimore, MD, USA) presented results of a very interesting prospective evaluation of progression and composition of coronary plaque among men in the Multicenter AIDS Cohort Study (MACS) performing baseline and follow-up coronary CT angiography in 409 men (253 HIV+, 156 HIV-; median interscan interval=4.5 yrs) (Abstract 77). Calcified and non-calcified plaque (NCP) volumes, including lipid-rich low attenuation plaque (LAP), were measured in each coronary segment. Mean age was 54 yrs (53 HIV+, 57 HIV-) and 32% were black (35% HIV+, 27% HIV-). HIV-infected participants were slightly younger (p<0.001), more likely to be African-American (p<0.001) and current smokers (p=0.003); they also had a slightly lower systolic blood pressure (p=0.02), higher fasting glucose (p=0.007) and lower HDL-cholesterol (p<0.001). 81% of HIV+ men were aviremic during the interval. There were 118 men (74 HIV+, 44 HIV-) with no baseline plaque. Incident plaque was seen in 36 (30%) men; 24 developed both NCP and calcified plaque (mixed plaque) and 12 developed only NCP. HIV+ men had a greater adjusted incidence of NCP (IRR 2.13, p=0.03), LAP (IRR 2.84, p=0.05) and mixed plaque (IRR 3.09, P=0.01) than HIV- men, especially among non-black men and independently of their viremic status.
David B. Hanna (Albert Einstein College of Medicine, Bronx, NY, USA) evaluated associations of carotid artery measurements using carotid artery intima-media thickness (cIMT) measured by ultrasound with all-cause mortality in the Women’s Interagency HIV Study (WIHS) and the Multicenter AIDS Cohort Study (MACS) (Abstract 78). Among 1,722 women (median age 40 years, 88% black or Hispanic, 71% HIV+, 62% on ART at baseline) and 880 men (median age 49, 35% black or Hispanic, 66% HIV+, 72% on ART), 10% (206 women, 83 men) died during follow-up. In adjusted analyses, cIMT was not associated with mortality. Presence of carotid artery plaque was associated with 56% greater mortality risk (95% CI 1.13-2.15) and varied by cohort (HR 1.25 among women, 95% CI 0.83-1.89; HR 2.48 among men, 95% CI 1.35-4.38; p for interaction 0.045); the greater the arterial stiffness (measured by Young’s modulus of elasticity) the greater was the mortality risk. Carotid artery measurements were independently associated with all-cause mortality in both HIV+ and HIV- persons.
Priscilla Hsue (University of California San Francisco, San Francisco, CA, USA) presented the impact of low dose methotrexate (LDMTX) on immune activation and endothelial function (assessed by flow-mediated vasodilation or FMD of the brachial artery) in treated and suppressed HIV-infected participants (Abstract 79). 176 Participants of this randomized placebo-controlled study (A5314) received weekly LDMTX or placebo (+ folic acid) for 24 weeks and were followed for an additional 12 weeks. Median change in CD4+ T-cells after 24 weeks was -58 (-163, 47) vs. 2 (-101,97) cells/mm3 in the LDMTX vs. placebo group (p=0.003) which resolved (p=0.09) by 36 weeks. Median change in CD8+ T-cells after 24 weeks was -103 (-228, 0) vs. -2 (-142, 84) cells/mm3 in the LDMTX vs. placebo group (p=0.001). Safety event rates were 12.8% (11 events) with LDMTX vs. 5.6% (5 events) with placebo (Δ=7.2%, upper 1-sided 90% CI=13.4%). FMD did not improve with LDMTX (Δ=0.09% [95% CI -0.67%, 0.85%]); hsCRP, IP-10, IL-6, sCD14, sCD163, D-Dimer, Fibrinogen, and sVCAM also did not change with LDMTX. There was a modest decrease in CD4+ T cell activation (absolute change of % CD3+CD4+CD38+HLADR+) at week 4 (p=0.05) that was significant at week 24 only (p<0.007), and a significant reduction in CD8+ T cell activation (absolute change of % CD3+CD8+CD38+HLADR+) at weeks 4, 12 and 24 (p<0.001 for all). LDMTX appeared to reduce arterial inflammation (by FDG-PET/CT) in a subset of 28 HIV+ individuals compared to placebo (Tawakol et al, Abstract 684 LB, CROI 2018).
Paddy W. Mallon (University College Dublin, Dublin, Ireland) studied results in platelet reactivity (measured by aggregometry) in a group of virologically suppressed PLWH switching away from ABC to tenofovir alafenamide (TAF) (platelet function substudy of a randomized double-blind trial of virally suppressed – study 1717) (Abstract 80). The 61 participants (29 in TAF/FTC and 32 in ABC/3TC group) were well matched at baseline. Although baseline platelet aggregation (PAg) in response to collagen (Col), thrombin receptor-activating peptide (TRAP) and adenosine diphosphate (ADP) was similar between groups, W4 PAg with Col, TRAP and ADP was significantly lower in the TAF/FTC arm (reflected by greater EC50, i.e. less reactive platelets) compared to the ABC/3TC arm. Reduced PAg in response to Col persisted through W12, while differences in PAg with TRAP and ADP were no longer significant at W12. Within a randomized trial, switching from ABC/3TC to TAF/FTC was associated with significantly early lower platelet reactivity induced by Col.