AIDS

Progressive phasing out of baseline CD4 cell count testing for people living with HIV in Kinshasa, DRC No abstract available

Long-term consequences of interpersonal violence experiences on treatment engagement and health status in people living with HIV Objective: To examine the impact of previous interpersonal violence (IPersV) experiences on long-term healthcare engagement and health outcomes in a large Canadian HIV-cohort. Design: People living with HIV (PLHIV) were screened for IPersV, and their healthcare outcomes over the nine subsequent years were analyzed. Methods: A total of 1064 PLHIV were screened for past and present IPersV experiences through semi-structured interviews. Follow-up included core treatment engagement (e.g., clinic visits) and health-status variables (HIV viral load, CD4 T-cell count, mortality, comorbidities), analysed descriptively and with longitudinal Cox regressions. Results: At intake, 385 (36%) PLHIV reported past or present IPersV including childhood (n = 224, 21%) or adulthood experiences (n = 161, 15%) and were offered conventional social work support. Over nine years, individuals with any IPersV experiences were 36% more likely to discontinue care, 81% more likely to experience viremia, 47% more likely to experience a drop in CD4 counts below 200/mm3, and 65% more likely to die compared to patients not reporting IPersV (p's <0.05). Outcomes were similar when adjusted for sociodemographic factors. Childhood IPersV in particular was linked to several of the outcomes, with higher rates of discontinuation of care, viremia, and mortality related to mental health/addiction or HIV-related complications. Conclusions: IPersV is associated with an increased risk over time of healthcare discontinuation, poorer long-term HIV-related health outcomes, and increased mortality, especially for patients victimized in childhood. Apart from targeted IPersV screening to initiate conventional supports (e.g., through social work), increased efforts to engage vulnerable populations in their long-term care seems warranted. Correspondence to Dr. Esther Fujiwara, Department of Psychiatry, University of Alberta, Edmonton, AB, Canada T6G 2V2. Tel.: 1+(780) 492-4104; fax: +1(780) 492-6841; e-mail: efujiwara@ualberta.ca Received 19 October, 2020 Revised 2 December, 2020 Accepted 7 December, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2020 Wolters Kluwer Health, Inc.

Combining traditional and molecular epidemiology methods to quantify local HIV transmission among foreign-born residents of King County, Washington Objectives: We evaluated the ability for molecular epidemiology to augment traditional HIV surveillance beyond the detection of clusters for outbreak investigation. To do this, we address a question of interest to Public Health – Seattle and King County: what proportion of HIV diagnoses among people born outside of the United States are acquired locally? Design: King County residents diagnosed with HIV, 2010–2018. Methods: We linked HIV-1 pol gene sequences to demographic information obtained from the National HIV Surveillance System, Public Health – Seattle and King County case investigation and partner services interviews. We determined the likely location of HIV acquisition based on HIV testing, travel histories and cluster-based molecular analyses. Results: Among 2409 people diagnosed with HIV, 798 (33%) were born outside of the United States. We inferred the location of acquisition for 77% of people born outside of the United States: 26% likely acquired HIV locally in King County (of whom 69% were MSM, 16% heterosexual), and 51% likely acquired HIV outside of King County (primarily outside of the United States). Of this 77% of people for whom we inferred the location of HIV acquisition, 45% were determined using traditional epidemiology methods and an additional 32% were inferred using molecular epidemiology methods. Conclusion: We found that the National HIV Surveillance System misclassified most HIV-infected foreign-born residents as 'new' local infections, and that these cases contribute to an overestimate of local incidence. Our findings highlight how molecular epidemiology can augment traditional HIV surveillance activities and provide useful information to local health jurisdictions beyond molecular cluster detection. Correspondence to Joshua T. Herbeck, Department of Global Health, International Clinical Research Center, University of Washington, Seattle, Washington, USA. E-mail: herbeck@uw.edu, rkerani@uw.edu Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2020 Wolters Kluwer Health, Inc.

Homonegativity, sexual violence and condom use with women in men who have sex with men and women in West Africa (CohMSM) Objective: The study aimed to explore longitudinal interactions between homonegativity and sexual behaviors with female partners among HIV-negative West African men who have sex with men and women (MSMW) Design and method: The community-based cohort CohMSM ANRS 12324 - Expertise France enrolled MSM in Togo, Burkina Faso, Côte d'Ivoire and Mali. Socio-behavioral data were collected every 6 months. Using 30-month follow-up data, a multiprobit analysis was performed to investigate the relationship between psychosocial and behavioral variables ex-ante (t-1) and ex-post (t). Results: MSMW (n = 326) accounted for half of all participants in CohMSM. They reported inconsistent condom use with women in 39% of visits. Perceived and internalized homonegativity at t-1 tended to lead to sexual violence towards women at t (p < 0.1), which was associated with inconsistent condom use with them at t (p < 0.05). Conclusion: Given the high HIV prevalence in West African MSM, widespread condom-less sex with women in MSMW, and the aggravating effect of social and internalized homonegativity, more research in the MSMW subpopulation is needed to assess the risk of HIV bridging to women and to design support activities. Correspondence to Marion Fiorentino, SESSTIM, Faculté de médecine, 27 bd Jean Moulin, 13005 Marseille FRANCE. Tél: +33 413 732 283; e-mail: marion.fiorentino@inserm.fr Received 8 January, 2020 Revised 21 February, 2020 Accepted 2 March, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2020 Wolters Kluwer Health, Inc.

Identifying influential neighbors in social networks and venue affiliations among young MSM: A data science approach to predict HIV infection Objective: Young men who have sex with men (YMSM) bear a disproportionate burden of HIV infection in the United States and their risks of acquiring HIV may be shaped by complex multi-layer social networks. These networks are formed through not only direct contact with social/sex partners but also indirect anonymous contacts encountered when attending social venues. We introduced a new application of a state-of-the-art graph-based deep learning method to predict HIV infection that can identify influential neighbors within these multiple network contexts. Design and Methods: We used empirical network data among YMSM aged 16–29 years old collected from Houston and Chicago in the U.S. between 2014 and 2016. A computational framework GAT-HIV (Graph Attention Networks for HIV) was proposed to predict HIV infections by identifying influential neighbors within social networks. These networks were formed by multiple relations comprised of social/sex partners and shared venue attendances, and using individual-level variables. Further, GAT-HIV was extended to combine multiple social networks using multi-graph GAT methods. A visualization tool was also developed to highlight influential network members for each individual within the multiple social networks. Results: The multi-graph GAT-HIV models obtained average AUC values of 0.776 and 0.824 for Chicago and Houston respectively, performing better than empirical predictive models (e.g. AUCs of random forest: 0.758 and 0.798). GAT-HIV on single networks also delivered promising prediction performances. Conclusions: The proposed methods provide a comprehensive and interpretable framework for graph-based modeling that may inform effective HIV prevention intervention strategies among populations most vulnerable to HIV. Correspondence to: Yang Xiang, Ph.D., Houston, TX United States;. e-mail: Yang.Xiang@uth.tmc.edu Received 7 June, 2020 Revised 19 October, 2020 Accepted 19 November, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2020 Wolters Kluwer Health, Inc.

ApoA-I mimetics attenuate macrophage activation in chronic treated HIV Objective(s): Despite antiretroviral therapy (ART), there is an unmet need for therapies to mitigate immune activation in HIV infection. The goal of this study is to determine whether the apoA-I mimetics 6F and 4F attenuate macrophage activation in chronic HIV. Design: Preclinical assessment of the in vivo impact of Tg6F and the ex vivo impact of apoA-I mimetics on biomarkers of immune activation and gut barrier dysfunction in treated HIV. Methods: We used two humanized murine models of HIV infection to determine the impact of oral Tg6F with ART (HIV+ART+Tg6F+) on innate immune activation (plasma human sCD14, sCD163) and gut barrier dysfunction [murine I-FABP, endotoxin (LPS), LPS binding protein (LBP), murine sCD14]. We also used gut explants from 10 uninfected and 10 HIV infected men on potent ART and no morbidity, to determine the impact of ex vivo treatment with 4F for 72 hours on secretion of sCD14, sCD163 and I-FABP from gut explants. Results: When compared to mice treated with ART alone (HIV+ART+), HIV+ART+Tg6F+ mice attenuated (i) macrophage activation (h-sCD14, h-sCD163), (ii) gut barrier dysfunction (m-IFABP, LPS, LBP and m-sCD14), iii) plasma and gut tissue oxidized lipoproteins. The results were consistent with independent mouse models and ART regimens. Both 4F and 6F attenuated shedding of I-FABP and sCD14 from gut explants from HIV infected and uninfected participants. Conclusions: Given that gut barrier dysfunction and macrophage activation are contributors to comorbidities like cardiovascular disease in HIV, apoA-I mimetics should be tested as therapy for morbidity in chronic treated HIV. Correspondence to Theodoros Kelesidis, M.D, PhD, Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. 10833 Le Conte Ave. CHS 37-121 Los Angeles, CA 90095, USA; e-mail: tkelesidis@mednet.ucla.edu Received 11 June, 2020 Revised 26 October, 2020 Accepted 18 November, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2020 Wolters Kluwer Health, Inc.

Minimal detection of cerebrospinal fluid escape after initiation of antiretroviral therapy in acute HIV-1 infection Objective: Despite suppression of HIV-1 replication in the periphery by antiretroviral therapy (ART), up to 10% of treated individuals have quantifiable HIV-1 in the CSF, termed CSF escape. CSF escape may be asymptomatic but has also been linked to progressive neurological disease, and may indicate persistence of HIV in the central nervous system (CNS). CSF escape has not yet been assessed after initiation of ART during acute HIV-1 infection (AHI). Design: Prospective cohort study. Setting: Major voluntary counseling and testing site in Bangkok, Thailand. Subjects: Participants identified and initiated on ART during AHI who received an optional study lumbar puncture at pre-ART baseline or after 24 or 96 weeks of ART. Main outcome measures: Paired levels of CSF and plasma HIV-1 RNA, with CSF > plasma HIV-1 RNA defined as CSF escape. Results: 204 participants had paired blood and CSF sampling in at least one visit at baseline, week 24, or week 96. 29 participants had CSF sampling at all three visits. CSF escape was detected in 1/90 at week 24 (CSF HIV-1 RNA 2.50 log10 copies/mL, plasma HIV-1 RNA < 50 copies/mL), and 0/55 at week 96. Conclusions: While levels of CSF HIV-1 RNA in untreated AHI are high, initiating treatment during AHI results in a very low rate of CSF escape in the first two years of treatment. Early treatment may improve control of HIV-1 within the CNS compared with treatment during chronic infection, which may have implications for long-term neurological outcomes and CNS HIV-1 persistence. Correspondence to Serena Spudich, MD, Professor, Department of Neurology, Yale University School of Medicine, 300 George Street, Room 8300c, New Haven, Connecticut, 06511 USA. Tel: +1 650 400 1222; e-mail: serena.spudich@yale.edu Received 28 May, 2020 Revised 8 July, 2020 Accepted 1 September, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2020 Wolters Kluwer Health, Inc.

Circulating extracellular vesicles as new inflammation marker in hiv infection Background: Extracellular Vesicles(EVs), released by cell pullulation, are surrounded by a phospholipid bilayer and carry proteins as well and genetic material. It has been shown that EVs mediate intercellular communication in several conditions, such as inflammation, immunodeficiency, tumor growth and viral infections. Here, we analyzed circulating levels of EVs in order to clarify their role in chronic inflammation mechanisms characterizing HIV patients. Methods: We analyzed and subtyped circulating levels of EVs, through a recently developed flow cytometry method. In detail, endothelial-derived EVs (CD31+/CD41a-/CD45-, EMVs), EVs stemming from leukocytes (CD45+, LMVs) and platelets (CD41a+/CD31+) were identified and enumerated. Moreover, we analyzed the EV protein cargo with proteomic analysis. Results: Circulating levels of total EVs, EMVs and LMVs were significantly lower in the HIV+ patients than in healthy subjects, while platelets-derived EVs resulted higher in patients than in the healthy population. Proteomic analysis showed the upregulation of gammaIFN and IL1alpha, and down-regulation of OSM, NF-kB, LIF and RXRA signaling resulted activated in this patients. Conclusion: These data demonstrate, for the first time, that HIV infection induces the production of EVs containing mediators that possibly feed the chronic inflammation and the viral replication. These two effects are connected since the inflammation itself induces the viral replication. We therefore hypothesize that HIV infection inhibits the production of EVs that carry anti-inflammatory molecules. Correspondence to Prof. Katia Falasca, Clinic of Infectious Diseases, Dept. of Medicine and Science of Aging, University "G. D'Annunzio" School of Medicine, Via dei Vestini, 66100 Chieti – Italy. Tel.: +39-0871-357562; fax: +39-0871-358372; e-mail: k.falasca@unich.it Received 7 August, 2020 Revised 14 October, 2020 Accepted 17 November, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2020 Wolters Kluwer Health, Inc.

Promoting antiretroviral therapy adherence habits: a novel approach based on a synthesis of economic and psychological theories of habit formation No abstract available

The relationship between smoking, current CD4, viral load and cancer in persons living with HIV Background: It is unknown if the carcinogenic effect of smoking is influenced by CD4 count and viral load (VL) in persons living with HIV. Material and Methods: RESPOND participants with known smoking status were included. Poisson regression adjusting for baseline confounders investigated the interaction between current CD4/VL strata (good [CD4≥500/mm3 and VL<200 copies/mL], poor [CD4≤350/mm3 and VL>200 copies/ml] and intermediate [all other combinations]), smoking status and all cancers, non-AIDS defining cancers (NADC), smoking-related cancers (SRC), and infection-related cancers (IRC). Results: Of 19602 persons, 41.3% were never smokers 44.4% current and 14.4% previous smokers at baseline. CD4/VL strata were poor in 3.4%, intermediate in 44.8% and good in 51.8%. There were 513 incident cancers; incidence rate 6.9/1000 PYFU (95% CI 6.3–7.5). Current smokers had higher incidence of all cancer (adjusted incidence rate ratio 1.45; 1.17–1.79), NADC (1.65; 1.31–2.09), SRC (2.21; 1.53–3.20), and IRC (1.38; 0.97–1.96) vs never smokers. Those with poor CD4/VL had increased incidence of all cancer (5.36; 95% CI 3.71–7.75), NADC (3.14; 1.92–5.14), SRC (1.82; 0.76–4.41) and IRC (10.21; 6.06–17.20) versus those with good CD4/VL. There was no evidence that the association between smoking and cancer subtypes differed depending on the CD4/VL strata (p > 0.1, test for interaction). Conclusions: In the large RESPOND consortium, the impact of smoking on cancer was clear and reducing smoking rates should remain a priority. The association between current immune deficiency, virological control and cancer was similar for never smokers, current smokers and previous smokers suggesting similar carcinogenic effects of smoking regardless of CD4 count and VL. Correspondence to Amanda Mocroft, Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, Rowland Hill St, London, NW3 2PF; e-mail: a.mocroft@ucl.ac.uk Received 1 September, 2020 Revised 30 November, 2020 Accepted 2 December, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2020 Wolters Kluwer Health, Inc.

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