Life Chaos is Associated with Reduced HIV Testing, Engagement in Care, and ART Adherence Among Cisgender Men and Transgender Women upon Entry into Jail.

Life chaos, the perceived inability to plan for and anticipate the future, may be a barrier to the HIV care continuum for people living with HIV who experience incarceration. Between December 2012 and June 2015, we interviewed 356 adult cisgender men and transgender women living with HIV in Los Angeles County Jail. We assessed life chaos using the Confusion, Hubbub, and Order Scale (CHAOS) and conducted regression analyses to estimate the association between life chaos and care continuum. Forty-eight percent were diagnosed with HIV while incarcerated, 14% were engaged in care 12 months prior to incarceration, mean antiretroviral adherence was 65%, and 68% were virologically suppressed. Adjusting for sociodemographics, HIV-related stigma, and social support, higher life chaos was associated with greater likelihood of diagnosis while incarcerated, lower likelihood of engagement in care, and lower adherence. There was no statistically significant association between life chaos and virologic suppression. Identifying life chaos in criminal-justice involved populations and intervening on it may improve continuum outcomes

Sex-Specific Heterosis in Line Crosses of Mice Selectively Bred for High Locomotor Activity

When populations with similar histories of directional selection are crossed, their offspring may differ in mean phenotype as compared with the average for the parental populations, often exhibiting enhancement of the mean phenotype (termed heterosis or hybrid vigor). We tested for heterosis in a cross of two replicate lines of mice selectively bred for high voluntary wheel running for 53 generations. Mice were paired to produce four sets of F1 offspring: two purebred High Runner (HR) lines and the hybrid reciprocal crosses. The purebred HR showed statistically significant, sex-dependent differences in body mass, wheel revolutions, running duration, mean running speed, and (controlling for body mass) organ masses (heart ventricles, liver, spleen, triceps surae muscle). Hybrid males ran significantly more revolutions than the purebred males, mainly via increased running speeds, but hybrid females ran intermediate distances, durations, and speeds, as compared with the purebred females. In both sexes, ventricles were relatively smaller in hybrids as compared with purebred HR. Overall, our results demonstrate differential and sex-specific responses to selection in the two HR lines tested, implying divergent genetic architectures underlying high voluntary exercise

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Life Chaos is Associated with Reduced HIV Testing, Engagement in Care, and ART Adherence Among Cisgender Men and Transgender Women upon Entry into Jail.

Life chaos, the perceived inability to plan for and anticipate the future, may be a barrier to the HIV care continuum for people living with HIV who experience incarceration. Between December 2012 and June 2015, we interviewed 356 adult cisgender men and transgender women living with HIV in Los Angeles County Jail. We assessed life chaos using the Confusion, Hubbub, and Order Scale (CHAOS) and conducted regression analyses to estimate the association between life chaos and care continuum. Forty-eight percent were diagnosed with HIV while incarcerated, 14% were engaged in care 12 months prior to incarceration, mean antiretroviral adherence was 65%, and 68% were virologically suppressed. Adjusting for sociodemographics, HIV-related stigma, and social support, higher life chaos was associated with greater likelihood of diagnosis while incarcerated, lower likelihood of engagement in care, and lower adherence. There was no statistically significant association between life chaos and virologic suppression. Identifying life chaos in criminal-justice involved populations and intervening on it may improve continuum outcomes

Using Microsimulation Modeling to Inform EHE Implementation Strategies in Los Angeles County

BackgroundPre-exposure prophylaxis (PrEP) is essential to ending HIV. Yet, uptake remains uneven across racial and ethnic groups. We aimed to estimate the impacts of alternative PrEP implementation strategies in Los Angeles County.SettingMen who have sex with men, residing in Los Angeles County.MethodsWe developed a microsimulation model of HIV transmission, with inputs from key local stakeholders. With this model, we estimated the 15-year (2021-2035) health and racial and ethnic equity impacts of 3 PrEP implementation strategies involving coverage with 9000 additional PrEP units annually, above the Status-quo coverage level. Strategies included PrEP allocation equally (strategy 1), proportionally to HIV prevalence (strategy 2), and proportionally to HIV diagnosis rates (strategy 3), across racial and ethnic groups. We measured the degree of relative equalities in the distribution of the health impacts using the Gini index (G) which ranges from 0 (perfect equality, with all individuals across all groups receiving equal health benefits) to 1 (total inequality).ResultsHIV prevalence was 21.3% in 2021 [Black (BMSM), 31.1%; Latino (LMSM), 18.3%, and White (WMSM), 20.7%] with relatively equal to reasonable distribution across groups (G, 0.28; 95% confidence interval [CI], 0.26 to 0.34). During 2021-2035, cumulative incident infections were highest under Status-quo (n = 24,584) and lowest under strategy 3 (n = 22,080). Status-quo infection risk declined over time among all groups but remained higher in 2035 for BMSM (incidence rate ratio, 4.76; 95% CI: 4.58 to 4.95), and LMSM (incidence rate ratio, 1.74; 95% CI: 1.69 to 1.80), with the health benefits equally to reasonably distributed across groups (G, 0.32; 95% CI: 0.28 to 0.35). Relative to Status-quo, all other strategies reduced BMSM-WMSM and BMSM-LMSM disparities, but none reduced LMSM-WMSM disparities by 2035. Compared to Status-quo, strategy 3 reduced the most both incident infections (% infections averted: overall, 10.2%; BMSM, 32.4%; LMSM, 3.8%; WMSM, 3.5%) and HIV racial inequalities (G reduction, 0.08; 95% CI: 0.02 to 0.14).ConclusionsMicrosimulation models developed with early, continuous stakeholder engagement and inputs yield powerful tools to guide policy implementation

Are Unequal Policies in Pre-Exposure Prophylaxis Uptake Needed to Improve Equality? An Examination Among Men Who Have Sex with Men in Los Angeles County

Racial and ethnic minority men who have sex with men (MSM) are disproportionately affected by HIV/AIDS in Los Angeles County (LAC), an important epicenter in the battle to end HIV. We examine tradeoffs between effectiveness and equality of pre-exposure prophylaxis (PrEP) allocation strategies among different racial and ethnic groups of MSM in LAC and provide a framework for quantitatively evaluating disparities in HIV outcomes. To do this, we developed a microsimulation model of HIV among MSM in LAC using county epidemic surveillance and survey data to capture demographic trends and subgroup-specific partnership patterns, disease progression, patterns of PrEP use, and patterns for viral suppression. We limit analysis to MSM, who bear most of the burden of HIV/AIDS in LAC. We simulated interventions where 3000, 6000, or 9000 PrEP prescriptions are provided annually in addition to current levels, following different allocation scenarios to each racial/ethnic group (Black, Hispanic, or White). We estimated cumulative infections averted and measures of equality, after 15 years (2021-2035), relative to base case (no intervention). By comparing allocation strategies on the health equality impact plane, we find that, of the policies evaluated, targeting PrEP preferentially to Black individuals would result in the largest reductions in incidence and disparities across the equality measures we considered. This result was consistent over a range of PrEP coverage levels, demonstrating that there are "win-win" PrEP allocation strategies that do not require a tradeoff between equality and efficiency

Trajectories of Viral Suppression in People Living With HIV Receiving Coordinated Care: Differences by Comorbidities.

BackgroundIn March of 2013, the Los Angeles County (LAC) Division of HIV and STD Programs implemented a clinic-based Medical Care Coordination (MCC) Program to increase viral suppression (VS) (<200 c/mL) among people living with HIV (PLWH) at high risk for poor health outcomes.ObjectiveThis study aimed to estimate trajectories of VS and to assess whether these trajectories differed by stimulant use, housing instability, and depressive symptom severity as reported by PLWH participating in MCC.MethodsData represent 6408 PLWH in LAC receiving services from the MCC Program and were obtained from LAC HIV surveillance data matched to behavioral assessments obtained across 35 Ryan White Program clinics participating in MCC. Piecewise mixed-effects logistic regression with a random intercept estimated probabilities of VS from 12 months before MCC enrollment through 36 months after enrollment, accounting for time by covariate interactions for 3 comorbid conditions: housing instability, stimulant use, and depressive symptoms.ResultsThe overall probability of VS increased from 0.35 to 0.77 within the first 6 months in the MCC Program, and this probability was maintained up to 36 months after enrollment. Those who reported housing instability, stimulant use, or multiple comorbid conditions did not achieve the same probability of VS by 36 months as those with none of those comorbidities.ConclusionsFindings suggest that MCC improved the probability of VS for all patient groups regardless of the presence of comorbidities. However, those with comorbid conditions will still require increased support from patient-centered programs to address disparities in VS

Immune response to a Trichinella spiralis infection in house mice from lines selectively bred for high voluntary wheel running.

Four lines of mice bred for high voluntary wheel running (HR lines) have high baseline circulating corticosterone levels and increased daily energy expenditure as compared with four non-selected control (C) lines. High corticosterone may suppress immune function and competing energy demands may limit ability to mount an immune response. We hypothesized that HR mice have a reduced immune response and therefore a decreased ability to fight an infection by Trichinella spiralis, an ecologically relevant nematode common in mammals. Infections have an acute, intestinal phase while the nematode is migrating, reproducing and traveling throughout the bloodstream, followed by a chronic phase with larvae encysted in muscles. Adult males (generation 55 of the selection experiment) were sham-infected or infected by oral gavage with ~300 J1 T. spiralis larvae. During the chronic phase of infection, mice were given wheel access for 6 days, followed by 2 days of maximum aerobic performance trials. Two weeks post-infection, infected HR had significantly lower circulating immunoglobulin E levels compared with infected C mice. However, we found no statistical difference between infected HR and C mice in numbers of encysted larvae within the diaphragm. As expected, both voluntary running and maximum aerobic performance were significantly higher in HR mice and lower in infected mice, with no line type-by-infection interactions. Results complement those of previous studies suggesting decreased locomotor abilities during the chronic phase of T. spiralis infection. However, despite reduced antibody production, breeding for high voluntary wheel exercise does not appear to have a substantial negative impact on general humoral function