Background Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because models have addressed slightly different questions and have reported different outcome metrics. This study compares the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART. Methods and Findings Twelve independent mathematical models evaluated a set of standardised ART intervention scenarios in South Africa and reported a common set of outputs. Intervention scenarios systematically varied the CD4 count threshold for treatment eligibility, access to treatment, and programme retention. For a scenario in which 80% of HIV-infected individuals start treatment on average 1 y after their CD4 count drops below 350 cells/µl and 85% remain on treatment after 3 y, the models projected that HIV incidence would be 35% to 54% lower 8 y after the introduction of ART, compared to a counterfactual scenario in which there is no ART. More variation existed in the estimated long-term (38 y) reductions in incidence. The impact of optimistic interventions including immediate ART initiation varied widely across models, maintaining substantial uncertainty about the theoretical prospect for elimination of HIV from the population using ART alone over the next four decades. The number of person-years of ART per infection averted over 8 y ranged between 5.8 and 18.7. Considering the actual scale-up of ART in South Africa, seven models estimated that current HIV incidence is 17% to 32% lower than it would have been in the absence of ART. Differences between model assumptions about CD4 decline and HIV transmissibility over the course of infection explained only a modest amount of the variation in model results. Conclusions Mathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all suggest that ART, at high levels of access and with high adherence, has the potential to substantially reduce new HIV infections. There was broad agreement regarding the short-term epidemiologic impact of ambitious treatment scale-up, but more variation in longer term projections and in the efficiency with which treatment can reduce new infections. Differences between model predictions could not be explained by differences in model structure or parameterization that were hypothesized to affect intervention impact. Please see later in the article for the Editors' Summary
Background-Although recent guidelines call for expanded routine screening for HIV, resources for antiretroviral treatment (ART) are limited and all eligible people are not currently being treated.
Nursing homes and other long-term care facilities account for a disproportionate share of COVID-19 cases and fatalities worldwide. Outbreaks in US nursing homes have persisted despite nationwide visitor restrictions beginning in mid-March. An early report issued by the Centers for Disease Control and Prevention identified staff members working in multiple nursing homes as a likely source of spread from the Life Care Center in Kirkland, WA, to other skilled nursing facilities. The full extent of staff connections between nursing homes—and the role these connections serve in spreading a highly contagious respiratory infection—is currently unknown given the lack of centralized data on cross-facility employment. We perform a large-scale analysis of nursing home connections via shared staff and contractors using device-level geolocation data from 50 million smartphones, and find that 5.1% of smartphone users who visited a nursing home for at least 1 h also visited another facility during our 11-wk study period—even after visitor restrictions were imposed. We construct network measures of connectedness and estimate that nursing homes, on average, share connections with 7.1 other facilities. Traditional federal regulatory metrics of nursing home quality are unimportant in predicting outbreaks, consistent with recent research. Controlling for demographic and other factors, a home’s staff network connections and its centrality within the greater network strongly predict COVID-19 cases.
Background— Treatment options for end-stage heart failure include inotrope-dependent medical therapy, orthotopic heart transplantation (OHT), left ventricular assist device (LVAD) as destination therapy or bridge to transplant. Methods and Results— We developed a state-transition model to simulate 4 treatment options and associated morbidity and mortality. Transition probabilities, costs, and utilities were estimated from published sources. Calculated outcomes included survival, quality-adjusted life-years, and incremental cost-effectiveness. Sensitivity analyses were performed on model parameters to test robustness. Average life expectancy for OHT-eligible patients is estimated at 1.1 years, with 39% surviving to 1 year. OHT with a median wait time of 5.6 months is estimated to increase life expectancy to 8.5 years, and costs <$100 000/quality-adjusted life-year gained, relative to inotrope-dependent medical therapy. Bridge to transplant-LVAD followed by OHT further is estimated to increase life expectancy to 12.3 years, for $226 000/quality-adjusted life-year gained versus OHT. Among OHT-ineligible patients, mean life expectancy with inotrope-dependent medical therapy is estimated at 9.4 months, with 26% surviving to 1 year. Patients who instead received destination therapy-LVAD are estimated to live 4.4 years on average from extrapolation of recent constant hazard rates beyond the first year. This strategy costs $202 000/quality-adjusted life-year gained, relative to inotrope-dependent medical therapy. Patient’s age, time on wait list, and costs associated with care influence outcomes. Conclusions— Under most scenarios, OHT prolongs life and is cost effective in eligible patients. Bridge to transplant-LVAD is estimated to offer >3.8 additional life-years for patients waiting ≥6 months, but does not meet conventional cost-effectiveness thresholds. Destination therapy-LVAD significantly improves life expectancy in OHT-ineligible patients. However, further reductions in adverse events or improved quality of life are needed for destination therapy-LVAD to be cost effective.
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