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ObjectiveCombination strategies generate health benefits through improved health outcomes among people living with HIV (PLHIV) and prevention of new infections. We aimed to determine health benefits attributable to improved health among PLHIV versus HIV prevention for a set of combination strategies in six US cities.DesignA dynamic HIV transmission model.MethodsUsing a model calibrated for Atlanta, Baltimore, Los Angeles, Miami, New York City (NYC) and Seattle, we assessed the health benefits of city-specific optimal combinations of evidence-based interventions implemented at publicly documented levels and at ideal (90% coverage) scale-up (2020-2030 implementation, 20-year study period). We calculated the proportion of health benefit gains (measured as quality-adjusted life-years) resulting from averted and delayed HIV infections; improved health outcomes among PLHIV; and improved health outcomes due to medication for opioid use disorder (MOUD).ResultsThe HIV-specific proportion of total benefits ranged from 68.3% (95% credible interval: 55.3-80.0) in Seattle to 98.5% (97.5-99.3) in Miami, with the rest attributable to MOUD. The majority of HIV-specific health benefits in five of six cities were attributable HIV prevention, and ranged from 33.1% (26.1-41.1) in NYC to 83.1% (79.6-86.6) in Atlanta. Scaling up to ideal service levels resulted in three to seven-fold increases in additional health benefits, mostly from MOUD, with HIV-specific health gains primarily driven by HIV prevention.ConclusionOptimal combination strategies generated a larger proportion of health benefits attributable to HIV prevention in five of six cities, underlining the substantial benefits of antiretroviral therapy engagement for the prevention of HIV transmission through viral suppression. Understanding to whom benefits accrue may be important in assessing the equity and impact of HIV investments.

BackgroundIn the USA, Black and Hispanic or Latinx individuals continue to be disproportionately affected by HIV. Applying a distributional cost-effectiveness framework, we estimated the cost-effectiveness and epidemiological impact of two combination implementation approaches to identify the approach that best meets the dual objectives of improving population health and reducing racial or ethnic health disparities.MethodsWe adapted a dynamic, compartmental HIV transmission model to characterise HIV micro-epidemics in six US cities: Atlanta, Baltimore, Los Angeles, Miami, New York, and Seattle. We considered combinations of 16 evidence-based interventions to diagnose, treat, and prevent HIV transmission according to previously documented levels of scale-up. We then identified optimal combination strategies for each city, with the distribution of each intervention implemented according to existing service levels (proportional services approach) and the racial or ethnic distribution of new diagnoses (between Black, Hispanic or Latinx, and White or other ethnicity individuals; equity approach). We estimated total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios of strategies implemented from 2020 to 2030 (health-care perspective; 20-year time horizon; 3% annual discount rate). We estimated three measures of health inequality (between-group variance, index of disparity, Theil index), incidence rate ratios, and rate differences for the selected strategies under each approach.FindingsIn all cities, optimal combination strategies under the equity approach generated more QALYs than those with proportional services, ranging from a 3·1% increase (95% credible interval [CrI] 1·4-5·3) in New York to more than double (101·9% [75·4-134·6]) in Atlanta. Compared with proportional services, the equity approach delivered lower costs over 20 years in all cities except Los Angeles; cost reductions ranged from $22·9 million (95% CrI 5·3-55·7 million) in Seattle to $579·8 million (255·4-940·5 million) in Atlanta. The equity approach also reduced incidence disparities and health inequality measures in all cities except Los Angeles.InterpretationEquity-focused HIV combination implementation strategies that reduce disparities for Black and Hispanic or Latinx individuals can significantly improve population health, reduce costs, and drive progress towards Ending the HIV Epidemic goals in the USA.FundingNational Institute on Drug Abuse.

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Lysine 5,6-aminomutase is an adenosylcobalamin and pyridoxa- 5'-phosphate-dependent enzyme that catalyzes a 1,2 rearrangement of the terminal amino group of DL-lysine and of L-β-lysine. We have solved the x-ray structure of a substrate-free form of lysine- 5,6-aminomutase from Clostridium sticklandii. In this structure, a Rossmann domain covalently binds pyridoxal-5'-phosphate by means of lysine 144 and positions it into the putative active site of a neighboring triosephosphate isomerase barrel domain, while simultaneously positioning the other cofactor, adenosylcobalam in, ≈25 A from the active site. In this mode of pyridoxal-5'-phosphate binding, the cofactor acts as an anchor, tethering the separate polypeptide chain of the Rossmann domain to the triosephosphate isomerase barrel domain. Upon substrate binding and transaldimination of the lysine-144 linkage, the Rossmann domain would be free to rotate and bring adenosylcobalamin, pyridoxal-5'-phosphate, and substrate into proximity. Thus, the structure embodies a locking mechanism to keep the adenosylcobalamin out of the active site and prevent radical generation in the absence of substrate. [ABSTRACT FROM AUTHOR]

Background: Sodium consumption raises blood pressure, increasing the risk for heart attack and stroke. Several countries, including the United States, are considering strategies to decrease population sodium intake. Objective: To assess the cost-effectiveness of 2 population strategies to reduce sodium intake: government collaboration with food manufacturers to voluntarily cut sodium in processed foods, modeled on the United Kingdom experience, and a sodium tax. Design: A Markov model was constructed with 4 health states: well, acute myocardial infarction (MI), acute stroke, and history of MI or stroke. Data Sources: Medical Panel Expenditure Survey (2006), Framingham Heart Study (1980 to 2003), Dietary Approaches to Stop Hypertension trial, and other published data. Target Population: U.S. adults aged 40 to 85 years. Time Horizon: Lifetime. Perspective: Societal. Outcome Measures: Incremental costs (2008 U.S. dollars), quality-adjusted life-years (QALYs), and MIs and strokes averted. Results of Base-Case Analysis: Collaboration with industry that decreases mean population sodium intake by 9.5% averts 513Â 885 strokes and 480Â 358 MIs over the lifetime of adults aged 40 to 85 years who are alive today compared with the status quo, increasing QALYs by 2.1 million and saving $32.1 billion in medical costs. A tax on sodium that decreases population sodium intake by 6% increases QALYs by 1.3 million and saves $22.4 billion over the same period. Results of Sensitivity Analysis: Results are sensitive to the assumption that consumers have no disutility with modest reductions in sodium intake. Limitation: Efforts to reduce population sodium intake could result in other dietary changes that are difficult to predict. Conclusion: Strategies to reduce sodium intake on a population level in the United States are likely to substantially reduce stroke and MI incidence, which would save billions of dollars in medical expenses. Primary Funding Source: Department of Veterans Affairs, Stanford University, and National Science Foundation.

Background: To help achieve Ending the HIV Epidemic (EHE) goals of reducing new HIV incidence, pre-exposure prophylaxis (PrEP) use and engagement must increase despite multidimensional barriers to scale-up and limitations in funding. We investigated the cost-effectiveness of interventions spanning the PrEP continuum of care., Setting: Men who have sex with men in Atlanta, GA, a focal jurisdiction for the EHE plan., Methods: Using a network-based HIV transmission model, we simulated lifetime costs, quality-adjusted life years (QALYs), and infections averted for 8 intervention strategies using a health sector perspective. Strategies included a status quo (no interventions), 3 distinct interventions (targeting PrEP initiation, adherence, or persistence), and all possible intervention combinations. Cost-effectiveness was evaluated incrementally using a $100,000/QALY gained threshold. We performed sensitivity analyses on PrEP costs, intervention costs, and intervention coverage., Results: Strategies averted 0.2%-4.2% new infections and gained 0.0045%-0.24% QALYs compared with the status quo. Initiation strategies achieved 20%-23% PrEP coverage (up from 15% with no interventions) and moderate clinical benefits at a high cost, while adherence strategies were relatively low cost and low benefit. Under our assumptions, the adherence and initiation combination strategy was cost-effective ($86,927/QALY gained). Sensitivity analyses showed no strategies were cost-effective when intervention costs increased by 60% and the strategy combining all 3 interventions was cost-effective when PrEP costs decreased to $1000/month., Conclusion: PrEP initiation interventions achieved moderate public health gains and could be cost-effective. However, substantial financial resources would be needed to improve the PrEP care continuum toward meeting EHE goals., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)