HIV

Background: With an annual budget of more than $2 billion, the Health Resources and Services Administration’s Ryan White HIV/AIDS Program (RWHAP) is the third largest source of public funding for HIV care and treatment in the United States, yet little analysis has been done to quantify the long-term public health and economic impacts of the federal program. Methods: Using an agent-based, stochastic model, we estimated health care costs and outcomes over a 50-year period in the presence of the RWHAP relative to those expected to prevail if the comprehensive and integrated system of medical and support services funded by the RWHAP were not available. We made a conservative assumption that, in the absence of the RWHAP, only uninsured clients would lose access to these medical and support services. Results: The model predicts that the proportion of people with HIV who are virally suppressed would be 25.2 percentage points higher in the presence of the RWHAP (82.6 percent versus 57.4 percent without the RWHAP). The number of new HIV infections would be 18 percent (190,197) lower, the number of deaths among people with HIV would be 31 percent (267,886) lower, the number of quality-adjusted life years (QALYs) would be 2.7 percent (5.6 million) higher, and cumulative health care costs would be 25 percent ($165 billion) higher in the presence of the RWHAP relative to the counterfactual. Based on these results, the RWHAP has an incremental cost-effectiveness ratio of $29,573 per QALY gained compared to the non-RWHAP scenario. Sensitivity analyses indicate that the probability of transmitting HIV via male-to-male sexual contact and the cost of antiretroviral medications have the largest effect on the cost-effectiveness of the program. Conclusions: The RWHAP would be considered very cost-effective when using standard guidelines of less than the per capita gross domestic product of the United States. The results suggest that the RWHAP plays a critical and cost-effective role in the United States’ public health response to the HIV epidemic. Corresponding Author: Boyd Gilman, PhD, Mathematica, Inc. 955 Massachusetts Ave., 801, Cambridge, MA 02138, Email: BGilman@mathematica-mpr.com, Phone: 617-301-8974 The authors report no conflicts of interest related to this work. Funding Source: This study was funded by the U.S. Department of Health and Human Services, Health Resources & Services Administration under contract number HHSH250201300018I. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Background: Preventable deaths, including those due to drug overdose (OD), are a significant public health concern in New York City (NYC); the rate of unintentional drug OD death in NYC increased 143% from 2010-2016. Trends in drug OD death among persons with HIV (PWH) in NYC have not been described. Methods: We selected PWH from the NYC HIV Registry who died during 2007-2017, resided in NYC at death, and died due to drug OD. We characterized PWH who died of drug OD and analyzed CD4 and viral load (VL) tests from surveillance to evaluate retention in care and viral suppression (VS) (VL…

Abstract: Background: Chronic immune activation and CD4+ T cell depletion are significant pathogenic features of HIV infection. Expression of Fas ligand (FasL), a key mediator of activation-induced cell death (AICD) in T cells, is elevated in people living with HIV-1 infection (PLWH). However, the epigenetic mechanisms underlying the enhanced induction of FasL expression in CD4+T lymphocytes in PLWH are not completely elucidated. Hence, the current work examined the effect of HIV infection on FasL promoter-associated histone modifications and transcriptional regulation in CD4+ T lymphocytes in PLWH. Method: Flow cytometric analysis was performed to examine the Fas-FasL expression on total CD4+ T cells as well as naïve/memory CD4+T cell subsets. Epigenetic FasL promoter histone modifications were investigated by chromatin immunoprecipitation (ChIP)-qPCR analysis using freshly isolated total CD4+ T lymphocytes from HIV-1 infected and non-infected individuals. Results: All naïve/memory CD4+ T cell subsets from PLWH showed markedly greater frequency of FasL expression. Notably, examination of functional outcome of FasL/Fas co-expression demonstrated the preferential susceptibility of Tcm and Tem subsets to activation-induced apoptosis. Importantly, these CD4+ T cells collectively demonstrated a distinct FasL promoter histone profile involving a coordinated cross-talk between histone H3 modifications leading to enhanced FasL gene expression. Specifically, levels of transcriptionally permissive histone H3K4-trimethylation (H3K4Me3) and histone H3K9-acetylation (H3K9Ac) were increased, with a concomitant decrease in the repressive H3K9-trimethylation (H3K9Me3). Conclusion: The present work demonstrates that epigenetic mechanisms involving promoter-histone modifications regulate transcriptional competence and FasL expression in CD4+ T cells from PLWH and render them susceptible to AICD. To whom correspondence should be addressed: Dr. Shirish Barve, Departments of Medicine and Pharmacology and Toxicology, University of Louisville Health Sciences Center, 505 S. Hancock St. CTR Bldg., Room 515, Louisville, KY 40202 USA, Tel. Phone: (502) 852-5245; Fax: (502) 852-8927; E-mail: shirishbarve@gmail.com Conflict of interest and Disclosures: The authors declare no conflict of interest. This work was supported by funding from RO1 AA024405, R01AA024405-02S1, P50 AA024337, U01AA026222 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Objectives Non-communicable diseases (NCDs) account for one-third of disability-adjusted life years in Malawi, and access to care is exceptionally limited. Integrated services with HIV are widely recommended, but few examples exist globally. We report descriptive outcomes from an Integrated Chronic Care Clinic (IC3). Design This is a retrospective cohort study. Setting The study includes an HIV–NCD clinic across 14 primary care facilities in the rural district of Neno, Malawi. Participants All new patients, including 6233 HIV–NCD diagnoses, enrolled between January 2015 and December 2017 were included. This included 3334 patients with HIV (59.7% women) and 2990 patients with NCD (67.3% women), 10% overall under age 15 years. Interventions Patients were seen at their nearest health centre, with a hospital team visiting routinely to reinforce staffing. Data were collected on paper forms and entered into an electronic medical record. Primary and secondary outcome measures Routine clinical measurements are reported at 1-year post-enrolment for patients with more than one visit. One-year retention is reported by diagnosis. Results NCD diagnoses were 1693 hypertension, 668 asthma, 486 epilepsy, 149 diabetes and 109 severe mental illness. By December 2018, 8.3% of patients with NCD over 15 years were also on HIV treatment. One-year retention was 85% for HIV and 72% for NCDs, with default in 8.4% and 25.5% and deaths in 4.0% and 1.4%, respectively. Clinical outcomes showed statistically significant improvement for hypertension, diabetes, asthma and epilepsy. Of the 1807 (80%) of patients with HIV with viral load results, 85% had undetectable viral load. Conclusions The IC3 model, built on an HIV platform, facilitated rapid decentralisation and access to NCD services in rural Malawi. Clinical outcomes and retention in care are favourable, suggesting that integration of chronic disease care at the primary care level poses a way forward for the large dual burden of HIV and chronic NCDs.…

Objective This study aimed to determine the prevalence of fatigue and the factors associated among adult people living with HIV attending antiretroviral therapy clinic in Gondar town, Ethiopia. Design Cross-sectional. Setting Governmental health facility that provides HIV care in Gondar town. Outcome measure Fatigue is defined by nine items version Fatigue Severity Scale. Participants Adult (aged 18 and above) people living with HIV in Gondar town (n=392). Result A total of 408 HIV seropositive adults were approached for consent, among which 392 participants consented to participate in this study, with a response rate of 96.1%. The mean age of the participants was 40.5±8.5 years. The prevalence of HIV-related fatigue was 53.3% and about 66% of women living with HIV experienced fatigue. The factors associated with fatigue experience were; female gender (adjusted OR (AOR): 2.61, 95% CI 1.01 to 5.3), being married (AOR: 0.18, 95% CI 0.10 to 0.9), low income (AOR: 7.1, 95% CI 4.6 to 22.15), unemployed (AOR: 2.79, 95% CI 1.19 to 9.84), parity (AOR: 4.87, 95% CI 2.18 to 17.9), being anaemic (AOR: 12.45, 95% CI 5.6 to 41.01), depression (AOR: 4.51, 95% CI 1.91 to 11.20), mild weight loss (AOR: 4.2 95% CI 2.56 to 13.9) and moderate weight loss (AOR: 5.1, 95% CI 1.85 to 16.12), respectively. Conclusion The findings of this study revealed that experiencing fatigue is quite common among adult people living with HIV. It is important for the healthcare professionals and people living with HIV to understand; the possible causes of fatigue, remedies and ways to reclaim energy. The predisposing factors and complications that cause fatigue should be aggressively diagnosed and treated by the clinicians. Further qualitative studies exploring the reasons for experiencing HIV-related fatigue might help designing interventions.…

Objective: To describe changes in maternal viral control over time in South African women living with HIV (WLHIV) using surveillance data from the National Health Laboratory Service's Corporate Data Warehouse (NHLS CDW). Design: A retrospective cohort analysis of maternal viral load (VL) during pregnancy and up to 15-months postpartum was performed amongst WLHIV (15–49 years) within the public-health sector between 2016-2017. Methods: HIV and pregnancy-related test data were used to create a synthetic cohort of pregnant WLHIV from the NHLS CDW. Syphilis-screening, in association with ward type and/or post-pregnancy cervical screening and/or birth HIV test and/or positive β-hCG, was used as a proxy for pregnancy. The syphilis-screening date marked the first antenatal care visit (fANC). Fractional polynomial models described VL evolution from fANC up to 15-months post-delivery. Piecewise linear regression models determined factors associated with VL decline. Findings: Among 178 319 pregnant WLHIV, 345 174 VL tests were performed [median = 2 (IQR: 2–3) per woman]. At fANC, 85 545 (48·0%) women were antiretroviral therapy (ART) experienced; 88 877 (49·8%) were not and 3 897 (2·2%) unknown. Proportions of viraemia (VL ≥50 copies/mL) were 39 756 (53·6%) at first VL performed during pregnancy, 14 780 (36·9%) at delivery and 24 328 (33·5%) postpartum. Maternal age ≥25 years, CD4 ≥500 and VL …

Objective: To determine the total annual cost per patient treated and total cost per patient retained on antiretroviral therapy in Zambia in conventional care in facilities and across community-based differentiated service delivery (DSD) models. Design: Economic evaluation using retrospective electronic record review. Setting: Twenty healthcare facilities (13 with DSD models and 7 as comparison sites) in 6 of Zambia's 10 provinces. Subjects, participants: All individuals on ART > 18 years old at the study sites, enrolled in a DSD model or conventional care by site type, respectively, with at least 12 months of follow-up data. Intervention: Accessing care through DSD models (community adherence groups (CAGs), urban adherence groups (UAGs), home ART delivery and care, and mobile ART services) or facility-based conventional care with 3-monthly visits. Main outcome measures: Total annual cost per patient treated and annual cost per patient retained in care 12 months after model enrolment. Retention in care was defined as attending a clinic visit at 12 months +/- 3 months. Results: The DSD models assessed cost more per patient/year than conventional care. Costs ranged from an annual $116 to $199 for the DSD models, compared with $100 for conventional care. CAGs and UAGs increased retention by 2% and 14%, respectively. All DSD models cost more per patient retained at 12 months than conventional care. The CAG had the lowest cost/patient retained for DSD models ($140–157). Conclusions: Though they achieve equal or improved retention in care, out-of-facility models of ART were more expensive than conventional care. Correspondence to Brooke E. Nichols, 801 Massachusetts Ave., Crosstown Center 3rd Floor, Room 304, Department of Global Health, Boston University School of Public Health, Boston, MA, USA. E-mail: brooken@bu.edu Received 8 June, 2020 Revised 21 August, 2020 Accepted 2 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.

Objective: To describe the natural history of individuals with congenital HIV who develop JC virus (JCV) infection of the central nervous system (CNS). Methods: We retrospectively evaluated individuals with congenital HIV who met criteria for progressive multifocal leukoencephalopathy (PML) or JCV granule cell neuronopathy (JCV GCN) at three major healthcare centers in the northeast USA. Data on adherence to combined antiretroviral therapy (cART), neurologic symptoms, serum markers of immunity and HIV infection, CSF analyses, radiographic features, modified Rankin Scale (mRS) scores, and survival were collected from the electronic medical record up to a censoring date of August 1, 2020. Results: Among 10 adults with congenitally acquired HIV, 9 were diagnosed with definitive PML and one was diagnosed with probable JCV GCN. Individuals presented at the time of their PML or JCV GCN diagnosis with a mean mRS of 2.0 (standard deviation 1.0). A premorbid mRS was documented for 6 patients and was zero in all cases. The most common risk factor was confirmed cART nonadherence in nine individuals. Five individuals with PML and one with JCV GCN died, with a latency from symptom onset to death of approximately 3 months for 3 individuals, and approximately 2 years for the remaining 2. Conclusion: Youth-adulthood transition is a high-risk point for dropping off from medical care. The study of this timepoint in people living with HIV could help inform effective care in these individuals. Correspondence to Caleb R.S. McEntire, MD, Neurology Resident, MGH-Brigham Healthcare, Brigham and Women's Hospital, 60 Fenwood Rd, 1st Floor, Boston, MA 02115. Tel: +215 370 1594; e-mail: cmcentire@mgh.harvard.edu Received 21 May, 2020 Revised 24 September, 2020 Accepted 14 October, 2020 Copyright © 2020 Wolters Kluwer Health, Inc.

Objectives: HIV-1 pre-treatment drug resistance (PDR) is a global concern. Our aim was to evaluate high-throughput sequencing (HTS) for HIV-1 resistance testing and describe PDR in Sweden, where 75% of diagnosed individuals are foreign-born. Design: Cross-sectional study. Methods: Individuals entering HIV-1 care in Sweden 2017- March 2019 (n = 400) were included if a viremic sample was available (n = 220). HTS was performed using an in-house assay. Drug resistance mutations (DRMs) (based on Stanford HIV DB v 8.7) at levels 1–5%, 5–19% and ≥20% of the viral population were described. Results from HTS and routine Sanger sequencing were compared. Results: HTS was successful in 88% of patients, 92% when viral load was ≥1000 copies/ml. DRMs at any level in protease (PR) and/or reverse transcriptase (RT) were detected in 95 individuals (49%), whereas DRMs ≥20% in 35 (18%) individuals. DRMs ≥20% correlated well to findings in routine Sanger sequencing. PR/RT DRMs ≥20% were predicted by treatment exposure; adjusted OR 9.28 (95% CI 2.24–38.43; p = 0.002) and origin in Asia; adjusted OR 20.65 (95% CI 1.66–256.24; p = 0.02). Non-nucleoside RT inhibitor (NNRTI) DRMs ≥20% were common (16%) and over-represented in individuals originating from sub-Saharan Africa or Asia. Low level integrase strand transfer inhibitor (INSTI) DRMs …

Background: Early infant diagnosis of HIV (EID) improves child survival through earlier initiation of antiretroviral therapy (ART). In many settings, ART initiation is hindered by delays in testing performed in centralized labs. Point-of-care (PoC) platforms offer opportunities to improve the timeliness of ART initiation. Methods: We used a mathematical model to estimate the costs and performance of on-site PoC testing using three platforms (m-PIMA, GeneXpert IV, and GeneXpert Edge) compared to the standard of care (SoC). Primary outcomes included ART initiation within 60 days of sample collection, HIV-related mortality before ART initiation, and incremental cost-effectiveness ratios (ICERs). Results: PoC testing significantly increased ART initiation within 60 days (from 19% with SoC to 82–84% with PoC) and decreased HIV-related mortality (from 23% with SoC to 5% with PoC). ART initiation and mortality were similar across PoC platforms. When only used for EID and with high coverage of prevention of mother-to-child transmission (PMTCT) programs, ICERs for PoC testing compared to the SoC ranged from $430-$1097 per additional infant on ART within 60 days and from $1527-$3888 per death averted. PoC-based testing was more cost-effective in settings with lower PMTCT coverage, greater delays in the SoC, and when PoC instruments could be integrated with other disease programs. Conclusions: Our findings illustrate that PoC platforms can dramatically improve the timeliness of EID and linkage to HIV care. The cost-effectiveness of PoC platforms depends on the cost of PoC testing, existing access to diagnostic testing, and the ability to integrate PoC testing with non-EID programs. Correspondence to Catherine G. Sutcliffe, 615 N. Wolfe St, Rm E6535, Baltimore, MD 21205, Tel: +410-614-5248; e-mail: csutcli1@jhu.edu Received 25 March, 2020 Revised 6 October, 2020 Accepted 12 October, 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.

Objectives: Elevated levels of interleukin-6 (IL-6), D-dimer, and C-reactive protein (hsCRP) are associated with increased incidence of comorbid disease and mortality among people living with HIV (PLWH). Prior studies suggest a genetic basis for these biomarker elevations in the general population. The study objectives are to identify the genetic basis for these biomarkers among PLWH. Methods: Baseline levels of hsCRP, D-dimer and IL-6, and single nucleotide polymorphisms (SNPs) were determined for 7,768 participants in three HIV treatment trials. Single variant analysis was performed for each biomarker on samples from each of three ethnic groups (African [AFR], Admixed American [AMR], European [EUR]) within each trial including covariates relevant to biomarker levels. For each ethnic group, the results were pooled across trials, then further pooled across ethnicities. Results: The transethnic analysis identified three, two and one known loci associated with hsCRP, D-dimer and IL-6 levels, respectively, and two novel loci, FGB and GCNT1, associated with D-dimer levels. Lead SNPs exhibited similar effects across ethnicities. Additionally, three novel, ethnic-specific loci were identified: CATSPERG associated with D-dimer in AFR and PROX1-AS1 and TRAPPC9 associated with IL-6 in AFR and AMR, respectively. Conclusions: Eleven loci associated with three biomarker levels were identified in PLWH from the three studies including six loci known in the general population and five novel loci associated with D-dimer and IL-6 levels. These findings support the hypothesis that host genetics may partially contribute to chronic inflammation in PLWH and help to identify potential targets for intervention of serious non-AIDS complications. Correspondence to Weizhong Chang, Laboratory of Human Retrovirology and Immunoinformatics, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA. E-mail: weizhong.chang@nih.gov Received 22 March, 2020 Revised 28 July, 2020 Accepted 12 October, 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). 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.

Objectives: To investigate the effectiveness, safety and reasons for premature discontinuation of direct-acting antivirals (DAAs) in a diverse population of HIV/HCV co-infected individuals in Europe. Methods: All HIV/HCV co-infected individuals in the EuroSIDA study that started interferon (IFN) free DAA treatment between 1/6/2014 and 1/3/2018 with ≥12 weeks of follow-up after treatment stop were included in this analysis. Sustained virological response (SVR) was defined as a negative HCV-RNA result ≥12 weeks after stopping treatment (SVR12). Logistic regression was used to explore factors associated with SVR12. Results: 1042 individuals started IFN-free DAA treatment after 1/6/2014 and were included, 862 (82.2%) had a known response to treatment, 789 (91.5%, 95% CI 89.7-93.4) of which achieved SVR12. There were no differences in SVR12 across regions of Europe (p=0.84). After adjustment, the odds of achieving SVR12 was lower in individuals that received sofosbuvir/simeprevir +/- RBV (aOR 0.21 (95% CI 0.08-0.53) or ombitasvir/paritaprevir/dasabuvir +/- RBV (aOR 0.46 (95% CI 0.22–1.00) compared to sofosbuvir/ledipasvir +/- RBV. 43 (4.6%) individuals had one or more components of their HCV regimen stopped early, most commonly due to toxicity (n=14); of these 14, 11 were treated with ribavirin. Increased bilirubin was the most common grade 3 or 4 laboratory adverse event (n=15.3%) and was related to treatment with atazanavir and ribavirin. Conclusions: Our findings from real-world data on HIV/HCV co-infected individuals across Europe show DAA treatment is well tolerated, and that high rates of SVR12 can be achieved in all regions of Europe. Corresponding author: Amanda Mocroft, Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL,Rowland Hill St, London, NW3 2PF, Email: a.mocroft@ucl.ac.uk The authors report no conflicts of interest related to this work. Funding: EuroSIDA was supported by the European Union’s Seventh Framework Programme for research, technological development and demonstration under EuroCoord grant agreement n° 260694. Current support includes unrestricted grants by ViiV Healthcare LLC, GlaxoSmithKline R&D Limited, Janssen Scientific Affairs, Janssen R&D, Bristol-Myers Squibb Company, Merck Sharp & Dohme Corp, Gilead Sciences. The participation of centres from Switzerland was supported by The Swiss National Science Foundation (Grant 148522). The study is also supported by a grant [grant number DNRF126] from the Danish National Research Foundation. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Background: HIV care continuum outcomes deteriorate among people returning from incarceration. Interventions to improve care outcomes post-incarceration have been characterized by substantial heterogeneity in approach, outcome metrics, and results. A large number of recently published interventions have not been systematically reviewed. Methods: We searched peer reviewed and scholarly databases for published and grey literature describing interventions to improve HIV care continuum outcomes among individuals released from prison or jail. We systematically screened quantitative and qualitative intervention reports published through 2018, then extracted and analyzed study data using a classification scheme that we developed for categorizing intervention levels and strategies. Results: We included 23 reports from peer-reviewed literature, two from grey literature, and two from conference abstracts (27 total). Seventeen studies were classified as individual-level, three as biomedical-level, two as organizational-level, and five as multilevel. Nine studies were randomized controlled trials, four of which reported power calculations. Fifteen studies were quasi-experimental; one was a case study. Eleven studies were conducted in prisons, seven in jails, and nine in both prisons and jails. Of 11 studies reporting hypothesis tests, five found statistically significant effect sizes on primary outcomes. Conclusion: Interventions that demonstrate post-release improvements in clinic attendance and viral suppression include patient navigation strategies, especially involving peer support, and substance use treatment strategies. Funding: NIH #5R34MH115777 Corresponding Author: Daniel Woznica, PhD, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland UNITED STATES Declaration of interests: We declare no competing interests. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Background: To describe the virologic and immunologic outcomes among people living with human immunodeficiency virus (PLHIV) co-infected with SARS-CoV-2. Setting: Wuhan, China. Methods: 35 co-infected patients were identified by matching the reported cases in National Notifiable Infectious Disease Report system for COVID-19 and HIV in Wuhan by time of April 19, 2020. Questionnaire-based survey and follow-up with blood sample collection were used to obtain characteristics before COVID-19 and after recovery. Non-parametric Mann-Whitney U test, Chi-square or Fisher’s exact test, Mcnemar test and Wilcoxon test were conducted. Results: Twenty of the 35 co-infected patients were identified as asymptomatic/mild/moderate COVID-19 (non-severe group) and 15 were identified as severe/critical (severe group). The severe and non-severe group had no differences in demographics, HIV baseline status, the intervals between last tests and follow-up tests for CD4+ cell count and HIV-1 viral load (all P>0.05). Overall, there was a significantly increased number of co-infected patients with HIV-1 viral load ≥20 copies/mL after recovery (P=0.008). The median viral load increased significantly after recovery in severe group (P=0.034) while no significant change of HIV-1 viral load was observed in non-severe group. Limited change of CD4+ cell count was found (all P>0.05). Conclusion: The co-infection of SARS-CoV-2 might put PLHIV at greater risk for HIV-1 viral rebound especially for severe/critical COVID-19 while had limited impacts on CD4+ cell count. Whether continuous ART against HIV infection would have significant impacts on CD4+ cell count among PLHIV co-infected with SARS-CoV-2 need further research. Correspondence: Nianhua Xie (NHX), Department of AIDS Prevention, Wuhan Center for Disease Control and Prevention, No.288 Machang Road, Jianghan District, Wuhan, Hubei, China, 430024; E-mail: xienh@whcdc.org; Fax: 86-27-85801709; Tel: 86-27-85802953, Xia Wang (XW), Department of AIDS Prevention, Wuhan Center for Disease Control and Prevention, No.288 Machang Road, Jianghan District,Wuhan, Hubei, China, 430024; E-mail: wangxia1973@163.com; Fax: 86-27-85801709; Tel: 86-27-85801875 Conflicts of Interest: None of the authors declared conflicts of interest. * RH and HY contributed equally to this manuscript Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

An amendment to this paper has been published and can be accessed via the original article.…

Abstract Background COVID-19 is novel infectious disease with an evolving understanding of its epidemiology and clinical manifestations. Severe cases developed life-threatening complications, such as respiratory failure, shock, and multiple organs dysfunction. Immunocompromised patients often present atypical presentations of viral infected diseases. Case presentation We report newly diagnosed HIV infections in two patients with COVID-19 in China. In our two cases, both patients with elevated IL-6 received Tocilizumab treatment, but did not present obvious therapeutic effect. Conclusions These cases highlight possible co-detection of known immunocompromised diseases such as HIV. The two cases we reported stressed the risk of misdiagnosis, especially during the pandemic of an infectious disease and the importance of extended testing even if in immune-compromised condition the immune state may be ignored.…

Abstract Background Globally, the majority of people living with HIV have no or only limited access to HIV drug resistance testing to guide the selection of antiretroviral drugs. This is of particular concern for children and adolescents, who experience high rates of treatment failure. The GIVE MOVE trial assesses the clinical impact and cost-effectiveness of routinely providing genotypic resistance testing (GRT) to children and adolescents living with HIV who have an unsuppressed viral load (VL) while taking antiretroviral therapy (ART). Methods GIVE MOVE is an open-label randomised clinical trial enrolling children and adolescents (≥6 months to

Background: Children living with HIV are reaching adulthood and transitioning to adult clinics. This study aimed to describe clinical and immunovirological status after transition in patients with perinatal HIV. Methods: Patients participating in the Spanish multicenter pediatric HIV cohort (CoRISpe) transferred to adult care (FARO cohort) from 1997 to 2016 were included. Clinical and immunovirological data were collected from 12 years old to last follow-up moment after transition (up to December 2017). We used mixed-effect models to analyze changes in CD4 counts or viral suppression and multivariate analysis for risk factors for virological failure (VF) and immune status after transition. Transition years were classified into five-year periods. Results: 332 youths were included. Median age at transition was 18 years (IQR: 16.3-18.9), 58.1% women. Median follow-up time after transition was 6.6 years (IQR: 4.6-9.8) and 11 patients (3.3%) died. Immunovirological status at transition improved over the last periods. Globally, VF decreased from 27.7% at transition to 14.4% at 3 years post-transition (p

Background: Helminth infections can modulate immunity to Mycobacterium tuberculosis (Mtb). However, the effect of helminths, including Schistosoma mansoni (SM), on Mtb infection outcomes is less clear. Furthermore, HIV is a known risk factor for tuberculosis (TB) disease and has been implicated in SM pathogenesis. Therefore, it is important to evaluate whether HIV modifies the association between SM and Mtb infection. Setting: HIV-infected and HIV-uninfected adults were enrolled in Kisumu County, Kenya between 2014 and 2017 and categorized into three groups based on Mtb infection status: Mtb-uninfected healthy controls (HC), latent TB infection (LTBI), and active TB disease. Participants were subsequently evaluated for infection with SM. Methods: We used targeted minimum loss estimation and super learning to estimate a covariate-adjusted association between SM and Mtb infection outcomes, defined as the probability of being HC, LTBI or TB. HIV status was evaluated as an effect modifier of this association. Results: SM was not associated with differences in baseline demographic or clinical features of participants in this study, nor with additional parasitic infections. Covariate-adjusted analyses indicated that infection with SM was associated with a 4% higher estimated proportion of active TB cases in HIV-uninfected individuals and a 14% higher estimated proportion of active TB cases in HIV-infected individuals. There were no differences in estimated proportions of LTBI cases. Conclusions: We provide evidence that SM infection is associated with a higher probability of active TB disease, particularly in HIV-infected individuals. Correspondence: Cheryl L. Day, Emory Vaccine Center, 954 Gatewood Rd NE, Room 1024, Atlanta, GA 30329, cday@emory.edu Conflicts of Interest and Source of Funding: This work was supported by the National Institute of Allergy and Infectious Diseases (5R01AI111948 to CLD and U19AI111211 to JDA, DK, JR, JDE, HMB, LAW, NRG, and CLD). NRG is supported by a Midcareer Investigator Award from the National Institute of Allergy and Infectious Diseases (K24AI114444). For the remaining authors, no conflicts of interest were declared. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Background: Several biomarkers of inflammation and coagulation were reported to be associated with HIV disease progression in different settings. Here we report the association between eleven biomarkers and medium-term mortality in HIV-infected West Africa adults. Methods: In Temprano ANRS 12136, ART-naïve HIV-infected adults with high CD4 counts were randomly assigned either to start ART immediately or defer ART until the WHO criteria were met. Participants who completed the 30-month trial follow-up were invited to participate in a post-trial phase (PTP). The PTP endpoint was all-cause death. We used multivariate Cox proportional models to analyze the association between baseline plasma biomarkers (IL-1ra, IL-6, sVCAM-1, sCD14, D-dimer, Fibrinogen, IP-10, sCD163, albumin, hsCRP, 16S rDNA) and all-cause death in the Temprano participants randomized to defer ART. Results: 477 patients (median age 35, 78% women, median CD4 count: 379 cells/mm3) were randomly assigned to defer starting ART until the WHO criteria were met. The participants were followed for 2646 person-years (median 5.8 years). In the follow-up, 89% of participants started ART and 30 died. In the multivariate analysis adjusted for the study center, sex, baseline CD4 count, isoniazid preventive therapy, plasma HIV-1 RNA, PBMC HIV-1 DNA and ART, the risk of death was significantly associated with baseline sVCAM-1 (≥ 1458 vs. < 1458: adjusted hazard ratio [aHR] 2.57, 95% CI 1.13-5.82) and sCD14 (≥ 2187 vs. < 2187: aHR 2.79, IQR 1.29-6.02) levels. Conclusion: In these sub-Saharan African adults with high CD4 counts, pre-ART plasma sVCAM-1 and sCD14 levels were independently associated with mortality. Correspondence to Laurence Weiss, Service d’Immunologie Clinique, Hôpital Européen Georges Pompidou, Faculté de Médecine Paris Descartes, Université de Paris ; 20 rue Leblanc, 75015 Paris, France. Tel: 33 (1) 56 09 3297; e-mail: laurence.weiss@aphp.fr. Conflicts of interest: The authors have no conflicts of interest to disclose. * Roseline Affi and Delphine Gabillard contributed equally to this manuscript # Laurence Weiss and Xavier Anglaret contributed equally to this manuscript Funding: French National Agency for AIDS and viral hepatitis research (ANRS, Paris, France; Grants ANRS 12136, ANRS 12224, ANRS 12253) Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking.

Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter.

Progressive immune dysfunction and the acquired immunodeficiency syndrome (AIDS) develop in most persons with untreated infection with human immunodeficiency virus type 1 (HIV-1) but in only approximately 20 to 30% of persons infected with HIV type 2 (HIV-2); among persons infected with both types, the natural history of disease progression is poorly understood.

Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations.

The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain.

There is considerable genetic diversity among viruses of different subtypes (designated A to J) in the major group of human immunodeficiency virus type 1 (HIV-1), the form of HIV that is dominant in the global epidemic. If available, HIV-1 sequences pre-dating the recognition of AIDS could be crucial in defining the time of origin and the subsequent evolution of these viruses in humans. The oldest known case of HIV-1 infection was reported to be that of a sailor from Manchester who died of an AIDS-like illness in 1959; however, the authenticity of this case has not been confirmed. Genetic analysis of sequences from clinical materials obtained from 1971 to 1976 from members of a Norwegian family infected earlier than 1971 showed that they carried viruses of the HIV-1 outlier group, a variant form that is mainly restricted to West Africa. Here we report the amplification and characterization of viral sequences from a 1959 African plasma sample that was previously found to be HIV-1 seropositive. Multiple phylogenetic analyses not only authenticate this case as the oldest known HIV-1 infection, but also place its viral sequence near the ancestral node of subtypes B and D in the major group, indicating that these HIV-1 subtypes, and perhaps all major-group viruses, may have evolved from a single introduction into the African population not long before 1959.