Mathematical Modeling and Cost-Effectiveness of Antiretroviral-Based HIV-1 Prevention Strategies

The human immunodeficiency virus, or HIV, is the virus that causes acquired immune deficiency syndrome (AIDS). There are currently 35 million people living with HIV, and each year there are more than two million new HIV infections worldwide. While HIV was spreading quickly across MSM communities in resource rich settings in the 1980s, HIV was also getting a strong foothold among heterosexuals across Africa, and later in Asia. The epidemic is now most strongly concentrated in sub-Saharan Africa, with 70% of the worlds’ HIV cases. There has been a rise in the number of new HIV infections in several countries and in specific risk groups such as among men who have sex with men (MSM) in Europe. In the Netherlands, the number of newly infected MSM rose 57% between 2001 and 2013. This increase is primarily attributed to increases in sexual risk behavior. Meanwhile, while there are still over a million new infections per year in sub-Saharan Africa, the number of new infections in sub-Saharan Africa has been decreasing. This decrease has been attributed primarily to 1) a decline in sexual risk behavior6 and 2) large-scale rollout of antiretroviral treatment. When patients are successfully on antiretroviral treatment, they cannot generally transmit their infection

Spinal cord injury in the emergency context: Review of program outcomes of a spinal cord injury rehabilitation program in Sri Lanka

Background: The final months of the conflict in Sri Lanka in 2009 resulted in massive displacement of the civilian population and a high volume of orthopedic trauma including spinal cord injury. In response to this need, Médecins Sans Frontières implemented a multidisciplinary rehabilitation program. Methods. Patients were admitted to the program if they had a spinal cord injury

Immersed boundary-finite element model of fluid-structure interaction in the aortic root

It has long been recognized that aortic root elasticity helps to ensure efficient aortic valve closure, but our understanding of the functional importance of the elasticity and geometry of the aortic root continues to evolve as increasingly detailed in vivo imaging data become available. Herein, we describe fluid-structure interaction models of the aortic root, including the aortic valve leaflets, the sinuses of Valsalva, the aortic annulus, and the sinotubular junction, that employ a version of Peskin's immersed boundary (IB) method with a finite element (FE) description of the structural elasticity. We develop both an idealized model of the root with three-fold symmetry of the aortic sinuses and valve leaflets, and a more realistic model that accounts for the differences in the sizes of the left, right, and noncoronary sinuses and corresponding valve cusps. As in earlier work, we use fiber-based models of the valve leaflets, but this study extends earlier IB models of the aortic root by employing incompressible hyperelastic models of the mechanics of the sinuses and ascending aorta using a constitutive law fit to experimental data from human aortic root tissue. In vivo pressure loading is accounted for by a backwards displacement method that determines the unloaded configurations of the root models. Our models yield realistic cardiac output at physiological pressures, with low transvalvular pressure differences during forward flow, minimal regurgitation during valve closure, and realistic pressure loads when the valve is closed during diastole. Further, results from high-resolution computations demonstrate that IB models of the aortic valve are able to produce essentially grid-converged dynamics at practical grid spacings for the high-Reynolds number flows of the aortic root

Partner notification for reduction of HIV-1 transmission and related costs among men who have sex with men: A mathematical modeling study

Background Earlier antiretroviral treatment initiation prevents new HIV infections. A key problem in HIV prevention and care is the high number of patients diagnosed late, as these undiagnosed patients can continue forward HIV transmission. We modeled the impact on the Dutch menwho-have-sex-with-men (MSM) HIV epidemic and cost-effectiveness of an existing partner notification process for earlier identification of HIV-infected individuals to reduce HIV transmission. Methods Reduction in new infections and cost-effectiveness ratios were obtained for the use of partner notification to identify 5% of all new diagnoses (Scenario 1) and 20% of all new diagnoses (Scenario 2), versus no partner notification. Costs and quality adjusted life years (QALYs) were assigned to each disease state and calculated over 5 year increments for a20 year period. Results Partner notification is predicted to avert 18-69 infections (interquartile range [IQR] 13-24; 51-93) over the course of 5 years countrywide to 221-830 (IQR 140-299; 530-1,127) over 20 years for Scenario 1 and 2 respectively. Partner notification was considered cost-effective in the short term, with increasing cost-effectiveness over time: from €41,476 -€41, 736 (IQR €40,529-€42,147; €40,791-€42,397) to €5,773 -€5,887 (€5,134-€7,196; €5,411-€6,552) per QAL

Targeted HCV core antigen monitoring among HIV-positive men who have sex with men is cost-saving

Introduction: The World Health Organization declared the goal of hepatitis Cvirus (HCV) elimination by 2030. Micro-elimination, which is the reduction of incidence to zero in targeted populations, is less complex and costly and may be the first step to prove whether elimination is feasible. Asuitable target group are HIV-positive men who have sex with men (MSM) because of their high-risk behaviour and high incidence rates. Moreover, HCV monitoring is integrated in HIV care. The current HCV monitoring approach is suboptimal and complex and may miss new HCV infections. Alternative monitoring strategies, based on alanine aminotransferase, HCV-PCRand HCV-core antigen (HCV-cAg), combined with immediate direct-acting antiviral (DAA) treatment, may be more effective in reducing new HCV infections. Methods: Adeterministic mathematical transmission model was constructed representing the Dutch HCV epidemic among HIV-positive MSM to compare different HCV monitoring strategies from 2018 onwards. We evaluated the epidemiological impact of alternative and intensified monitoring in MSM with HCV. In addition, the cost-effectiveness was calculated over a lifetime horizon. Results: Current HCV monitoring and treatment is projected to result in an incidence of 1.1/1000 person-years, 0.24% prevalence, at a cost of 61.8 million (interquartile range 52.2-73.9). Compared with current monitoring, intensified monitoring will result in a maximum 27% reduction of incidence and 33% in prevalence at an increased cost. Conversely, compared with current monitoring, targeted HCV-cAg monitoring will result in a comparable incidence (1.1/1000 person-years) and prevalence (0.23%) but will be 1 million cheaper with increased quality-adjusted life year. Conclusion: Targeted monitoring reduces the HCV epidemic in a cost-saving manner; however, micro-elimination may not be obtained by 2030, highlighting the need for harm-reduction programmes

UK Public Sector Information and Re-use Policy – A 2008 Analysis

INTRODUCTION: Earlier antiretroviral therapy (ART) initiation reduces HIV-1 incidence. This benefit may be offset by increased transmitted drug resistance (TDR), which could limit future HIV treatment options. We analyze the epidemiological impact and cost-effectiveness of strategies to reduce TDR. METHODS: We develop a deterministic mathematical model representing Kampala, Uganda, to predict the prevalence of TDR over a 10-year period. We then compare the impact on TDR and cost-effectiveness of: (1) introduction of pre-therapy genotyping; (2) doubling use of second-line treatment to 80% (50-90%) of patients with confirmed virological failure on first-line ART; and (3) increasing viral load monitoring from yearly to twice yearly. An intervention can be considered cost-effective if it costs less than three times the gross domestic product per capita per quality adjusted life year (QALY) gained, or less than $3420 in Uganda. RESULTS: The prevalence of TDR is predicted to rise from 6.7$1612 to $2234 (IQR$450-dominated) per QALY gained. CONCLUSIONS: While earlier treatment initiation will result in a predicted increase in the proportion of patients infected with drug-resistant HIV, the absolute numbers of patients infected with drug-resistant HIV is predicted to decrease. Increasing use of second-line treatment to all patients with confirmed failure on first-line therapy is a cost-effective approach to reduce TDR. Improving access to second-line ART is therefore a major priority

Augmented Reality in Astrophysics

Augmented Reality consists of merging live images with virtual layers of information. The rapid growth in the popularity of smartphones and tablets over recent years has provided a large base of potential users of Augmented Reality technology, and virtual layers of information can now be attached to a wide variety of physical objects. In this article, we explore the potential of Augmented Reality for astrophysical research with two distinct experiments: (1) Augmented Posters and (2) Augmented Articles. We demonstrate that the emerging technology of Augmented Reality can already be used and implemented without expert knowledge using currently available apps. Our experiments highlight the potential of Augmented Reality to improve the communication of scientific results in the field of astrophysics. We also present feedback gathered from the Australian astrophysics community that reveals evidence of some interest in this technology by astronomers who experimented with Augmented Posters. In addition, we discuss possible future trends for Augmented Reality applications in astrophysics, and explore the current limitations associated with the technology. This Augmented Article, the first of its kind, is designed to allow the reader to directly experiment with this technology.Comment: 15 pages, 11 figures. Accepted for publication in Ap&SS. The final publication will be available at link.springer.co

Cost-effectiveness of adoption strategies for point of care HIV viral load monitoring in South Africa

Background: Viral load (VL) testing is recommended for monitoring people on ART. The National Health Laboratory Service (NHLS) in South Africa conducts >5million laboratory-based VL tests but faces challenges with specimen integrity and results delivery. Point-of-care (POC) VL monitoring may improve VL suppression (VLS). We assessed the cost-effectiveness of different strategies for POC testing in South Africa. Methods: We developed a cost-outcome model utilizing NHLS data, including facility-level annual VL volumes, proportion with VLS, specimen rejection rates, turn-around-time, and the cost/test. We assessed the impact of adopting POC VL technology under 4 strategies: (1) status-quo; (2) targeted POC testing at facilities with high levels of viral failure; (3) targeted POC testing at low-performing facilities; (4) complete POC adoption. For each strategy, we determined the total cost, effectiveness (expected number of virally suppressed people) and incremental cost-effectiveness ratio (ICER) based on expected (>10%) VLS improvement. Findings: Existing laboratory-based VL testing costs $126 m annually and achieves 85.2$40/additional person suppressed, compared to the status-quo. Should resources allow, complete POC adoption may be cost-effective (ICER: $136/additional person suppressed), requiring an additional$49 m annually and achieving 94.5% VLS. All other strategies were dominated in the incremental analysis. Interpretation: Assuming POC VL monitoring confers clinical benefits, the most cost-effective strategy for POC adoption in South Africa is a targeted approach with POC VL technologies placed at facilities with high level of viral failure. Funding: Funding support from the Bill & Melinda Gates Foundation

Health outcomes and cost-effectiveness of monoclonal SARS-CoV-2 antibodies as pre-exposure prophylaxis

IMPORTANCE Pre-exposure prophylaxis with neutralizing SARS-CoV-2 monoclonal antibodies (mAbs PrEP) prevents infection and reduces hospitalizations and the duration thereof for COVID-19 and death among high-risk individuals. However, reduced effectiveness due to a changing SARS-CoV-2 viral landscape and high drug prices remain substantial implementation barriers.OBJECTIVE To assess the cost-effectiveness of mAbs PrEP as COVID-19 PrEP.DESIGN, SETTING, AND PARTICIPANTS For this economic evaluation, a decision analytic model was developed and parameterized with health care outcome and utilization data from individuals with high risk for COVID-19. The SARS-CoV-2 infection probability, mAbs PrEP effectiveness, and drug pricing were varied. All costs were collected from a third-party payer perspective. Data were analyzed from September 2021 to December 2022.MAIN OUTCOMES AND MEASURES Health care outcomes including new SARS-CoV-2 infections, hospitalization, and deaths. The cost per death averted and cost-effectiveness ratios using a threshold for prevention interventions of $22000 or less per quality-adjusted life year (QALY) gained.RESULTS The clinical cohort consisted of 636 individuals with COVID-19 (mean [SD] age 63 [18] years; 341 [54$275 and 75% or higher effectiveness. With a 100% effectiveness mAbs PrEP can reduce ward admissions by 70%, ICU admissions by 97%, and deaths by 92%. Drug prices, however, need to reduce to $550 for cost-effectiveness ratios less than$22000 per QALY gained per death averted and to $2200 for ratios between$22000 and $88000.CONCLUSIONS AND RELEVANCE In this study, use of mAbs PrEP for preventing SARS-CoV-2 infections was cost-saving at the beginning of an epidemic wave (high infection probability) with 75$275. These results are timely and relevant for decision-makers involved in mAbs PrEP implementation. When newer mAbs PrEP combinations become available, guidance on implementation should be formulated ensuring a fast rollout. Nevertheless, advocacy for mAbs PrEP use and critical discussion on drug prices are necessary to ensuring cost-effectiveness for different epidemic settings.Clinical epidemiolog