Let's treat everyone with HIV now: what happens next?

The effectiveness of antiretroviral therapy (ART) in the treatment and prevention of HIV infection has been firmly established and is no longer subject to debate. The earliest possible ART preserves immune function, prevents infection and neoplasms, and prevents the sexual transmission of HIV. Almost all HIV treatment guidelines now recommend ART initiation at the time of diagnosis, and UNAIDS and the 2015 US National HIV/AIDS Strategy (NHAS) have described plans to detect and treat 85–90% of people with HIV infection, regardless of disease stage

HIV Viral Suppression and Pre-exposure Prophylaxis in HIV and Syphilis Contact Tracing Networks: An Analysis of Disease Surveillance and Prescription Claims Data

Background: HIV and syphilis contact tracing networks offer efficient platforms for HIV treatment and prevention interventions, but intervention coverage within these networks has not been characterized. Setting: HIV and syphilis sexual contact tracing networks among men who have sex with men (MSM) in North Carolina (NC). Methods: Using surveillance data, we identified 2 types of "network events" that occurred between January 2013 and June 2017 among MSM in NC: being diagnosed with early syphilis or being named as a recent sexual contact of a person diagnosed with HIV or early syphilis. We estimated prevalent and incident HIV viral suppression among persons diagnosed with HIV before the network event, and we assessed the effect of contact tracing services on a 6-month cumulative incidence of viral suppression among previously HIV-diagnosed, virally unsuppressed persons. Using linked prescription claims data, we also evaluated prevalent and incident pre-exposure prophylaxis (PrEP) use in an insured subset of HIV-negative network members. Results: Viral suppression prevalence among previously HIV-diagnosed persons was 52.6%. The 6-month cumulative incidence of viral suppression was 35.4% overall and 13.1 (95% confidence interval: 8.8 to 17.4) percentage points higher among persons reached than among those not reached by contact tracing services. Few HIV-negative persons had prevalent (5.4%) or incident (4.1%) PrEP use in the 6 months before or after network events, respectively. Conclusions: Suboptimal viral suppression and PrEP use among MSM in NC in HIV/syphilis contact tracing networks indicate a need for intensified intervention efforts. In particular, expanded services for previously HIV-diagnosed persons could improve viral suppression and reduce HIV transmission within these networks

Parent Skills Training: Expanding School-Based Services for Adolescent Mothers

This article reports the results of a collaborative intervention effort between a teen-parent program and a school of social work Social work faculty and students participated in a program aimed at strengthening parental skills and the utilization of social support among adolescent mothers who were enrolled in a special high school program. The results of this evaluation study point to additional factors, such as empathy training and stress management, which need to be included in a comprehensive service-delivery program for school-age mothers.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68359/2/10.1177_104973159200200203.pd

Synthesis, characterization and thermochemistry of synthetic Pb–As, Pb–Cu and Pb–Zn jarosites

The enthalpy of formation from the elements of well characterized Pb-As, Pb-Cu, and Pb-Zn synthetic jarosites, corresponding to chemical formulas (H3O)0.68±0.03Pb0.32±0.002Fe2.86±0.14(SO4)1.69±0.08(AsO4)0.31±0.02(OH)5.59±0.28(H2O)0.41±0.02, (H3O)0.67±0.03Pb0.33±0.02Fe2.71±0.14Cu0.25±0.01(SO4)2±0.00(OH)5.96±0.30(H2O)0.04±0.002 and (H3O)0.57±0.03Pb0.43±0.02Fe2.70±0.14Zn0.21±0.01(SO4)2±0.00(OH)5.95±0.30(H2O)0.05±0.002, was measured by high temperature oxide melt solution calorimetry and gave ΔH°f = -3691.2 ± 8.6 kJ/mol, ΔH°f = -3653.6 ± 8.2 kJ/mol, and ΔH°f = -3669.4 ± 8.4 kJ/mol, respectively. Using estimated entropies, the standard Gibbs free energy of formation from elements at 298 K ΔG°f of the three compounds were calculated to be -3164.8 ± 9.1 kJ/mol, -3131.4 ± 8.7 kJ/mol, and -3153.6 ± 8.9 kJ/mol, respectively. Based on these free energies, their logKsp values are -13.94 ± 1.89, -4.38 ± 1.81 and -3.75 ± 1.80, respectively. For this compounds, a log10{Pb2+} - pH diagram is presented. The diagram shows that the formation of Pb-As jarosite may decrease aqueous arsenic and lead concentrations to meet drinking water standards. The new thermodynamic data confirm that transformation of Pb-As jarosite to plumbojarosite is thermodynamically possible

The role of depression in secondary HIV transmission among people who inject drugs in Vietnam: A mathematical modeling analysis

Background Among people who inject drugs (PWID), depression burden is high and may interfere with HIV prevention efforts. Although depression is known to affect injecting behaviors and HIV treatment, its overall impact on HIV transmission has not been quantified. Using mathematical modeling, we sought to estimate secondary HIV transmissions and identify differences by depression among PWID. Methods We analyzed longitudinal data from 455 PWID living with HIV in Vietnam during 2009–2013. Using a Bernoulli process model with individual-level viral load and behavioral data from baseline and 6-month follow-up visits, we estimated secondary HIV transmission events from participants to their potentially susceptible injecting partners. To evaluate differences by depression, we compared modeled transmissions per 1,000 PWID across depressive symptom categories (severe, mild, or no symptoms) in the three months before each visit. Results We estimated a median of 41.2 (2.5th, 97.5th percentiles: 33.2–49.2) secondary transmissions from all reported acts of sharing injection equipment with 833 injecting partners in the three months before baseline. Nearly half (41%) of modeled transmissions arose from fewer than 5% of participants in that period. Modeled transmissions per 1,000 PWID in that period were highest for severe depressive symptoms (100.4, 80.6–120.2) vs. mild (87.0, 68.2–109.4) or no symptoms (78.9, 63.4–94.1). Transmission estimates fell to near-zero at the 6-month visit. Conclusions Secondary transmissions were predicted to increase with depression severity, although most arose from a small number of participants. Our findings suggest that effective depression interventions could have the important added benefit of reducing HIV transmission among PWID. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose

Estimating the Effect of Depression on HIV Transmission Risk Behaviors Among People Who Inject Drugs in Vietnam: A Causal Approach

The burden of depression and HIV is high among people who inject drugs (PWID), yet the effect of depression on transmission risk behaviors is not well understood in this population. Using causal inference methods, we analyzed data from 455 PWID living with HIV in Vietnam 2009–2013. Study visits every 6 months over 2 years measured depressive symptoms in the past week and injecting and sexual behaviors in the prior 3 months. Severe depressive symptoms (vs. mild/no symptoms) increased injection equipment sharing (risk difference [RD] = 3.9 percentage points, 95% CI −1.7, 9.6) but not condomless sex (RD = −1.8, 95% CI −6.4, 2.8) as reported 6 months later. The cross-sectional association with injection equipment sharing at the same visit (RD = 6.2, 95% CI 1.4, 11.0) was stronger than the longitudinal effect. Interventions on depression among PWID may decrease sharing of injection equipment and the corresponding risk of HIV transmission. Clinical trial registration ClinicalTrials.gov NCT01689545

SARS-CoV-2 Mitigation Strategies, Testing, and Cases at 254 Jails in the US Southeast, October 2020 to May 2021

Objectives. To characterize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mitigation strategies, testing, and cases across county jails in the Southeastern United States, examining variability by jail characteristics. Methods. We administered a 1-time telephone survey to personnel of 254 jails in Alabama, Georgia, North Carolina, and South Carolina between October 2020 and May 2021. Results. Some SARS-CoV-2 mitigation strategies (e.g., screening at intake, isolation and masking for symptomatic persons) were commonly reported (≥ 75% of jails). Other measures, such as masking regardless of symptoms (52%) and screening at release (26%), were less common and varied by jail state or population size. Overall, 41% of jails reported no SARS-CoV-2 testing in the past 30 days. Jails with testing (59%) tested a median of 6 per 100 incarcerated persons; of those jails, one third reported 1 or more cases of positive tests. Although most jails detected no cases, in the 20% of all jails with 1 or more case in the past 30 days, 1 in 5 tests was positive. Conclusions. There was low testing coverage and variable implementation of SARS-CoV-2 mitigation strategies in Southeastern US jails during the first year of the COVID-19 pandemic

Depression, antiretroviral therapy initiation, and HIV viral suppression among people who inject drugs in Vietnam

Background: The burden of depression is high among people who inject drugs (PWID) and may contribute to the spread of HIV through poor treatment engagement and persistent viremia. We estimated the effects of depression on antiretroviral therapy (ART) initiation and viral suppression among PWID living with HIV. Methods: Longitudinal data were collected from 455 PWID living with HIV in Vietnam during 2009–2013. We estimated the 6- and 12-month cumulative incidence of ART initiation and viral suppression, accounting for time-varying confounding, competing events, and missing data. The cumulative incidence difference (CID) contrasted the incidence of each outcome had participants always vs. never experienced severe depressive symptoms across study visits to date. Results: Severe depressive symptoms decreased the cumulative incidence of ART initiation, with CID values comparing always vs. never having severe depressive symptoms of -7.5 percentage points (95% CI: -17.2, 2.2) at 6 months and -7.1 (95% CI: -17.9, 3.7) at 12 months. There was no appreciable difference in the cumulative incidence of viral suppression at 6 months (CID = 0.3, 95% CI: -11.3, 11.9) or 12 months (CID = 2.0, 95% CI: -21.8, 25.8). Limitations: Discrepancies between the ART initiation and viral suppression outcomes could be due to under-reporting of ART use and missing data on viral load. Conclusions: Future work probing the seemingly antagonistic effect of depression on treatment uptake – but not viral suppression – will inform the design of interventions promoting HIV clinical outcomes and reducing onward transmission among PWID

Limitations of the UNAIDS 90-90-90 metrics: a simulation-based comparison of cross-sectional and longitudinal metrics for the HIV care continuum

OBJECTIVES: The Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 and other cross-sectional metrics can lead to potentially counterintuitive conclusions when used to evaluate health systems' performance. This study demonstrates how time and population dynamics impact UNAIDS 90-90-90 metrics in comparison with a longitudinal analogue. DESIGN: A simplified simulation representing a hypothetical population was used to estimate and compare inference from UNAIDS 90-90-90 metrics and longitudinal metrics based on Kaplan-Meier-estimated 2-year probability of transition between stages. METHODS: We simulated a large cohort over 15 years. Everyone started out at risk for HIV, and then transitioned through the HIV care continuum based on fixed daily probabilities of acquiring HIV, learning status, entering care, initiating antiretroviral therapy (ART), and becoming virally suppressed, or dying. We varied the probability of ART initiation over three five-year periods (low, high, and low). We repeated the simulation with an increased probability of death. RESULTS: The cross-sectional probability of being on ART among persons who were diagnosed responded relatively slowly to changes in the rate of ART initiation. Increases in ART initiation rates caused apparent declines in the cross-sectional probability of being virally suppressed among persons who had initiated ART, despite no changes in the rate of viral suppression. In some cases, higher mortality resulted in the cross-sectional metrics implying improved healthcare system performance. The longitudinal continuum was robust to these issues. CONCLUSION: The UNAIDS 90-90-90 care continuum may lead to incorrect inference when used to evaluate health systems performance. We recommend that evaluation of HIV care delivery include longitudinal care continuum metrics wherever possible

Trisomy 21 activates the kynurenine pathway via increased dosage of interferon receptors

Altres ajuts: This work has also been supported by a "Marató TV3" grant (20141210 to J.F. and 044412 to R.B.).Trisomy 21 (T21) causes Down syndrome (DS), affecting immune and neurological function by ill-defined mechanisms. Here we report a large metabolomics study of plasma and cerebrospinal fluid, showing in independent cohorts that people with DS produce elevated levels of kynurenine and quinolinic acid, two tryptophan catabolites with potent immunosuppressive and neurotoxic properties, respectively. Immune cells of people with DS overexpress IDO1, the rate-limiting enzyme in the kynurenine pathway (KP) and a known interferon (IFN)-stimulated gene. Furthermore, the levels of IFN-inducible cytokines positively correlate with KP dysregulation. Using metabolic tracing assays, we show that overexpression of IFN receptors encoded on chromosome 21 contribute to enhanced IFN stimulation, thereby causing IDO1 overexpression and kynurenine overproduction in cells with T21. Finally, a mouse model of DS carrying triplication of IFN receptors exhibits KP dysregulation. Together, our results reveal a mechanism by which T21 could drive immunosuppression and neurotoxicity in DS