Large-Scale Telemedicine Implementation for Outpatient Clinicians: Results From a Pandemic-Adapted Learning Collaborative.

Learning collaboratives are seldom used outside of health care quality improvement. We describe a condensed, 10-week learning collaborative ("Telemedicine Hack") that facilitated telemedicine implementation for outpatient clinicians early in the COVID-19 pandemic. Live attendance averaged 1688 participants per session. Of 1005 baseline survey respondents, 57% were clinicians with one-third identifying as from a racial/ethnic minoritized group. Practice characteristics included primary care (71%), rural settings (51%), and community health centers (28%). Of three surveys, a high of 438 (81%) of 540 clinicians had billed ≥1 video-based telemedicine visit. Our learning collaborative "sprint" is a promising model for scaling knowledge during emergencies and addressing health inequities.

A randomized controlled trial showing safety and efficacy of a whole sporozoite vaccine against endemic malaria.

A highly effective malaria vaccine remains elusive despite decades of research. Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine), a metabolically active, nonreplicating, whole parasite vaccine demonstrated safety and vaccine efficacy (VE) against endemic P. falciparum for 6 months in Malian adults receiving a five-dose regimen. Safety, immunogenicity, and VE of a three-dose regimen were assessed in adults in Balonghin, Burkina Faso in a two-component study: an open-label dose escalation trial with 32 participants followed by a double-blind, randomized, placebo-controlled trial (RCT) with 80 participants randomized to receive three doses of 2.7 × 106 PfSPZ (N = 39) or normal saline (N = 41) just before malaria season. To clear parasitemia, artesunate monotherapy was administered before first and last vaccinations. Thick blood smear microscopy was performed on samples collected during illness and every 4 weeks for 72 weeks after last vaccinations, including two 6-month malaria transmission seasons. Safety outcomes were assessed in all 80 participants who received at least one dose and VE for 79 participants who received three vaccinations. Myalgia was the only symptom that differed between groups. VE (1 - risk ratio; primary VE endpoint) was 38% at 6 months (P = 0.017) and 15% at 18 months (0.078). VE (1 - hazard ratio) was 48% and 46% at 6 and 18 months (P = 0.061 and 0.018). Two weeks after the last dose, antibodies to P. falciparum circumsporozoite protein and PfSPZ were higher in protected versus unprotected vaccinees. A three-dose regimen of PfSPZ Vaccine demonstrated safety and efficacy against malaria infection in malaria-experienced adults.

Measuring the impact of the Affordable Care Act Medicaid expansion on access to primary care using an interrupted time series approach.

BACKGROUND: The Patient Protection and Affordable Care Act of 2010, commonly referred to as the Affordable Care Act (ACA), was created to increase access to primary care, improve quality of care, and decrease healthcare costs. A key provision in the law that mandated expansion of state Medicaid programme changed when states were given the option to voluntarily expand Medicaid. Our study sought to measure the impact of ACA Medicaid expansion on preventable hospitalization (PH) rates, a measure of access to primary care. METHODS: We performed an interrupted time series analysis of quarterly hospitalization rates across eight states from 2012 to 2015. Segmented regression analysis was utilized to determine the impact of policy reform on PH rates. RESULTS: The Affordable Care Act's Medicaid expansion led to decreased rates of PH (improved access to care); however, the finding was not significant (coefficient estimate: -0.0059, CI -0.0225, 0.0107, p = 0.4856). Healthcare system characteristics, such as Medicaid spending per enrollee and Medicaid income eligibility, were associated with a significant decrease in rates of PH (improved access to care). However, the Medicaid-to-Medicare fee index (physician reimbursement) and states with a Democratic state legislature had a significant increase in rates of PH (poor access to care). CONCLUSION: Health policy reform and healthcare delivery characteristics impact access to care. Researchers should continue evaluating such policy changes across more states over longer periods of time. Researchers should translate these findings into cost analysis for state policy-makers to make better-informed decisions for their constituents. CONTRIBUTION TO KNOWLEDGE: Ambulatory care-sensitive conditions are a feasible method for evaluating policy and measuring access to primary care. Policy alone cannot improve access to care. Other factors (trust, communication, policy-makers' motivations and objectives, etc.) must be addressed to improve access.

Ablation of the calpain-targeted site in cardiac myosin binding protein-C is cardioprotective during ischemia-reperfusion injury.

Cardiac myosin binding protein-C (cMyBP-C) phosphorylation is essential for normal heart function and protects the heart from ischemia-reperfusion (I/R) injury. It is known that protein kinase-A (PKA)-mediated phosphorylation of cMyBP-C prevents I/R-dependent proteolysis, whereas dephosphorylation of cMyBP-C at PKA sites correlates with its degradation. While sites on cMyBP-C associated with phosphorylation and proteolysis co-localize, the mechanisms that link cMyBP-C phosphorylation and proteolysis during cardioprotection are not well understood. Therefore, we aimed to determine if abrogation of cMyBP-C proteolysis in association with calpain, a calcium-activated protease, confers cardioprotection during I/R injury. Calpain is activated in both human ischemic heart samples and ischemic mouse myocardium where cMyBP-C is dephosphorylated and undergoes proteolysis. Moreover, cMyBP-C is a substrate for calpain proteolysis and cleaved by calpain at residues 272-TSLAGAGRR-280, a domain termed as the calpain-target site (CTS). Cardiac-specific transgenic (Tg) mice in which the CTS motif was ablated were bred into a cMyBP-C null background. These Tg mice were conclusively shown to possess a normal basal structure and function by analysis of histology, electron microscopy, immunofluorescence microscopy, Q-space MRI of tissue architecture, echocardiography, and hemodynamics. However, the genetic ablation of the CTS motif conferred resistance to calpain-mediated proteolysis of cMyBP-C. Following I/R injury, the loss of the CTS reduced infarct size compared to non-transgenic controls. Collectively, these findings demonstrate the physiological significance of calpain-targeted cMyBP-C proteolysis and provide a rationale for studying inhibition of calpain-mediated proteolysis of cMyBP-C as a therapeutic target for cardioprotection.

The effect of the global financial crisis on preventable hospitalizations among the homeless in New York State.

Objective Periods of economic instability may increase preventable hospitalizations because of increased barriers to accessing primary care. For underserved populations such as the homeless, these barriers may be more pronounced due to limited resources in the health care safety net. This study examined the impact of the global financial crisis of 2007-2008 on access to care for the homeless in New York State. Methods Hospitalizations for ambulatory care sensitive conditions (ACSCs) were used as a proxy measure for primary care access. Admissions for ACSCs were identified in the New York State Inpatient Database from 2006 to 2012. Hospitalization rates for ACSCs were calculated for the homeless and nonhomeless. Multivariable linear regression was used to investigate the impact of the financial crisis on hospitalization rates for ACSCs. Results The findings indicate that during the financial crisis, homeless adults had significantly higher preventable hospitalizations than nonhomeless adults, and the uninsured homeless had significantly higher preventable hospitalizations when compared to other homeless subgroups. After the financial crisis, preventable hospitalizations for the homeless stabilized but remained at higher rates than those for the nonhomeless. Conclusions These findings are important to developing health policies designed to provide effective care for underserved population such as the homeless.

Effect of the Economic Recession on Primary Care Access for the Homeless.

Primary care access (PCA) for the homeless can prove challenging, especially during periods of economic distress. In the United States, the most recent recession may have presented additional barriers to accessing care. Limited safety-net resources traditionally used by the homeless may have also been used by the non-homeless, resulting in delays in seeking treatment for the homeless. Using hospitalizations for ambulatory care sensitivity (ACS) conditions as a proxy measure for PCA, this study investigated the recession's impact on PCA for the homeless and non-homeless in four states. The State Inpatient Databases were used to identify ACS admissions. Findings from this study indicate the recession was a barrier to PCA for homeless people who were uninsured. Ensuring that economically-disadvantaged populations have the ability to obtain insurance coverage is crucial to facilitating PCA. With targeted outreach efforts, the Affordable Care Act provides an opportunity for expanding coverage to the homeless.

Medicaid managed care reduces readmissions for youths with type 1 diabetes.

OBJECTIVES: To determine whether the likelihood of readmission (adjusted for severity on first admission) for pediatric type 1 diabetes (T1D) differs between Medicaid managed care and non-managed care. STUDY DESIGN: De-identified patients were retrospectively selected from the Pediatric Health Information Systems database of the Children's Hospital Association (CHA). The cohort of 42 hospitals across 25 states included discharges between 2008 and 2011 for patients who were receiving Medicaid at the time of service and had T1D as their diagnosis. METHODS: Multiple factors and co-variants for readmission were analyzed by logistic regression, including age, race, gender, severity of illness, and state of admission. RESULTS: Of 14,544 T1D discharges with Medicaid, 4985 were readmitted, including 1792 readmitted for diabetic ketoacidosis (DKA). Despite similar rates of DKA between the managed care and non-managed care cohorts, overall 90-day readmission was 1.12 times more likely for Medicaid patients on non-managed care plans than those on managed care (odds ratio, 1.12; range = 1.04-1.20; both adjusted for severity of illness). Significant contributors were race, age, and gender; the relationship of location (state) and days between readmissions was also significant. The conservative estimate of cost reduction from Medicaid managed care related to lower readmission rate for pediatric T1D across CHA institutions between 2008 and 2011 was $2.6 million. CONCLUSIONS: From the largest, national, defined cohort available for contemporary study, youths with T1D on Medicaid managed care plans were less likely to be readmitted within 90 days of discharge.

Activation of hERG3 channel stimulates autophagy and promotes cellular senescence in melanoma.

Ion channels play a major factor in maintaining cellular homeostasis but very little is known about the role of these proteins in cancer biology. In this work we have discovered that, the Kv11.3 (hERG3) a plasma-membrane potassium channel plays a critical role in the regulation of autophagy in a cancer cell model. We have found that pharmacologic stimulation of the Kv11.3 channel with a small molecule activator, NS1643 induced autophagy via activation of an AMPK-dependent signaling pathway in melanoma cell line. In addition, we have found that NS1643 produced a strong inhibition of cell proliferation by activating a cellular senescence program. Furthermore, inhibition of autophagy via siRNA targeting AMPK or treatment with hydroxychloroquine an autophagy inhibitor activates apoptosis in NS1643-treated cells. Thus, we propose that, Kv11.3 is a novel mediator of autophagy, autophagy can be a survival mechanism contributing to cellular senescence, and that use of a combinatorial pharmacologic approach of Kv11.3 activator with inhibitors of autophagy represents a novel therapeutic approach against melanoma.

Master Settlement Agreement (MSA) spending and tobacco control efforts.

We investigate whether the distributions to the states from the Tobacco Master Settlement Agreement (MSA) in 1998 is associated with stronger tobacco control efforts. We use state level data from 50 states and the District of Columbia from four time periods post MSA (1999, 2002, 2004, and 2006) for the analysis. Using fixed effect regression models, we estimate the relationship between MSA disbursements and a new aggregate measure of strength of state tobacco control known as the Strength of Tobacco Control (SoTC) Index. Results show an increase of $1 in the annual per capita MSA disbursement to a state is associated with a decrease of -0.316 in the SoTC mean value, indicating higher MSA payments were associated with weaker tobacco control measures within states. In order to achieve the initial objectives of the MSA payments, policy makers should focus on utilizing MSA payments strictly on tobacco control activities across states.

Azelastine desensitization of transient receptor potential vanilloid 1: a potential mechanism explaining its therapeutic effect in nonallergic rhinitis.

BACKGROUND: Capsaicin, a prototypic transient receptor potential vanilloid 1 (TRPV1) agonist, has been shown to be more clinically effective in the treatment of nonallergic rhinitis (NAR) compared with other rhinitis subtypes. Azelastine has also been found to be clinically effective in the treatment of NAR but its mechanism(s) of action is still poorly elucidated. This study was designed to determine, using in vitro cell lines, whether topical therapies including azelastine have activity on TRPV1 ion channels similar to capsaicin. METHODS: The effects of capsaicin (1 µM), azelastine (30 µM), bepotastine (10 µM), olopatadine (10 µM), and fluticasone (200 µM) on TRPV1 channels using mice neuronal cells (Cath.a), as surrogates for submucosal sensory neurons, and human nasal epithelial cells (hNEC) were determined and compared. For azelastine, bepotastine, and capsaicin, which elicited an agonist effect on TRPV1, live cell [Ca(2+)] signaling in Cath.a cells and hNECs expressing TRPV1 were performed in the absence and presence of capsazepine at 10 µM (a TRPV1 antagonist) or using wild-type mouse embryonic fibroblasts (wtMEFs) that express TRPV1 ion channels and TRPV1 homozygous null mutant (TRPV1-/-) knockout MEF cells as controls to establish TRPV1 channel selectivity. As azelastine has previously been found clinically effective in NAR, additional experiments were performed to determine its ability to desensitize TRPV1 ion channels and its effect on regulating intracellular calcium homeostasis. RESULTS: Cath.a cells treated with azelastine, bepotastine, or capsaicin showed a significant increase in TRPV1-dependant (Ca(2+)) specific cytosolic fluorescence. Continuous treatment with azelastine or capsaicin resulted in desensitization of TRPV1 channels. In hNECs, azelastine stimulation resulted in Ca(2+) shifts from the cytosol to mitochondria and overexpression of hematopoietic cell-specific Lyn substrate 1-associated protein X1, which may thus be effective in cytosolic Ca(2+) homeostasis. CONCLUSION: Azelastine, similar to capsaicin, exhibits direct activity on TRPV1 ion channels that may represent a novel mechanistic pathway explaining its clinical efficacy in NAR.

Public health and high volume hydraulic fracturing.

High-volume horizontal hydraulic fracturing (HVHF) in unconventional gas reserves has vastly increased the potential for domestic natural gas production. HVHF has been promoted as a way to decrease dependence on foreign energy sources, replace dirtier energy sources like coal, and generate economic development. At the same time, activities related to expanded HVHF pose potential risks including ground- and surface water contamination, climate change, air pollution, and effects on worker health. HVHF has been largely approached as an issue of energy economics and environmental regulation, but it also has significant implications for public health. We argue that public health provides an important perspective on policymaking in this arena. The American Public Health Association (APHA) recently adopted a policy position for involvement of public health professionals in this issue. Building on that foundation, this commentary lays out a set of five perspectives that guide how public health can contribute to this conversation.

Distribution, burden, and impact of acute gastroenteritis in Dominica, 2009-2010.

Acute gastroenteritis (AGE) is an important public-health issue in Dominica. To determine the burden of AGE in Dominica, a retrospective, cross-sectional population survey was conducted in March-April 2009 and October 2010 (low- and-high-AGE seasons) and a laboratory survey from April 2009 to March 2010. The overall monthly prevalence of self-reported AGE was 8.6 % (95% CI 7.0-10.6); the incidence rate was 1.1 episodes/person-year and 79,157.1 episodes of AGE for the total population/year. Monthly prevalence of AGE was the highest in the 1-4 year(s) age-group (25.0%), higher in females (10.8%) and also varied by health district, with the highest monthly prevalence of AGE being reported in the Portsmouth district (13.1%). This difference in gender and across the health region was statistically significant. The estimated underreporting of syndromic AGE to the Ministry of Health was 83.3%. Furthermore, for every reported laboratory-confirmed case of AGE and foodbome disease (FBD), there was an estimated underreporting factor of 280. Overall, 47% of AGE specimens tested were positive for FBD pathogens. The predominant pathogens isolated were norovirus, followed by Giardia, Salmonella, and Shigella. The total annual estimated cost of AGE was US$ 1,371,852.92, and the total cost per capita due to AGE was US$ 19.06, indicating an economic burden of AGE-related illness on a small island of Dominica.

Key stakeholder perceptions regarding acute care psychiatry in distressed publicly funded mental health care markets.

The role of acute care inpatient psychiatry, public and private, has changed dramatically since the 1960s, especially as recent market forces affecting the private sector have had ripple effects on publicly funded mental health care. Key stakeholders' experiences, perceptions, and opinions regarding the role of acute care psychiatry in distressed markets of publicly funded mental health care were examined. A qualitative research study was conducted using semi-structured thematic interviews with 52 senior mental health system administrators, clinical directors and managers, and nonclinical policy specialists. Participants were selected from markets in six regions of the United States that experienced recent significant closures of acute care psychiatric beds. Qualitative data analyses yielded findings that clustered around three sets of higher order themes: structure of care, service delivery barriers, and outcomes. Structure of care suggests that acute care psychiatry is seen as part of a continuum of services; service delivery barriers inhibit effective delivery of services and are perceived to include economic, regulatory, and political factors; outcomes include fragmentation of mental health care services across the continuum, the shift of mental health care to the criminal justice system, and market-specific issues affecting mental health care. Findings delineate key stakeholders' perceptions regarding the role acute care psychiatry plays in the continuum of care for publicly funded mental health and suggest that public mental health care is inefficacious. Results carry implications for policy makers regarding strategies/policies to improve optimal utilization of scarce resources for mental health care, including greater focus on psychotherapy.

The Master Settlement Agreement and its impact on tobacco use 10 years later: lessons for physicians about health policy making.

The issue of tobacco industry responsibility for population health problems and compensation for their treatment has been growing since the 1960s. In 1999, the state attorneys general collectively launched the largest class action lawsuit in US history and sued the tobacco industry to recover the costs of caring for smokers. In what became known as the Master Settlement Agreement (MSA), states were rewarded billions of dollars and won concessions regarding how cigarettes could be advertised and targeted to minors. Ten years after this settlement, much is known about how MSA monies were distributed and how states have used the money. There is some understanding about how much of the money went toward offsetting the health-care costs attributable to smoking and whether resources were allocated to efforts to reduce smoking in a particular state. However, there are few data on what effect, if any, the MSA had on tobacco control locally and nationally. This commentary explores these issues, as well as how the tobacco industry has evolved to offset the losses incurred by the settlement. Finally, an analysis of the complexities of current tobacco policy making is provided so that physicians and other health-care advocacy groups can more completely understand the present-day political dynamics and be more effective in shaping tobacco control policy in the future.

Comparison of Markov model and discrete-event simulation techniques for HIV.

BACKGROUND: Markov models have been the standard framework for predicting long-term clinical and economic outcomes using the surrogate marker endpoints from clinical trials. However, they are complex, have intensive data requirements and are often difficult for decision makers to understand. Recent developments in modelling software have made it possible to use discrete-event simulation (DES) to model outcomes in HIV. Using published results from 48-week trial data as model inputs, Markov model and DES modelling approaches were compared in terms of clinical outcomes at 5 years and lifetime cost-effectiveness estimates. METHODS: A randomly selected cohort of 100 antiretroviral-naive patients with a mean baseline CD4+ T-cell count of 175 cells/mm3 treated with lopinavir/ritonavir was selected from Abbott study M97-720. Parameter estimates from this cohort were used to populate both a Markov and a DES model, and the long-term estimates for these cohorts were compared. The models were then modified using the relative risk of undetectable viral load as reported for atazanavir and lopinavir/ritonavir in the published BMS 008 study. This allowed us to compare the mean cost effectiveness of the models. The clinical outcomes included mean change in CD4+ T-cell count, and proportion of subjects with plasma HIV-1 RNA (viral load [VL]) <50 copies/mL, VL 50-400 copies/mL and VL >400 copies/mL. US wholesale acquisition costs (year 2007 values) were used in the mean cost-effectiveness analysis, and the cost and QALY data were discounted at 3%. RESULTS: The results show a slight predictive advantage of the DES model for clinical outcomes. The DES model could capture direct input of CD4+ T-cell count, and proportion of subjects with plasma HIV-1 RNA VL <50 copies/mL, VL 50-400 copies/mL and VL >400 copies/mL over a 48-week period, which the Markov model could not. The DES and Markov model estimates were similar to the actual clinical trial estimates for 1-year clinical results; however, the DES model predicted more detailed outcomes and had slightly better long-term (5-year) predictive validity than the Markov model. Similar cost estimates were derived from the Markov model and the DES. Both models predict cost savings at 5 and 10 years, and over a lifetime for the lopinavir/ritonavir treatment regimen as compared with an atazanavir regimen. CONCLUSION: The DES model predicts the course of a disease naturally, with few restrictions. This may give the model superior face validity with decision makers. Furthermore, this model automatically provides a probabilistic sensitivity analysis, which is cumbersome to perform with a Markov model. DES models allow inclusion of more variables without aggregation, which may improve model precision. The capacity of DES for additional data capture helps explain why this model consistently predicts better survival and thus greater savings than the Markov model. The DES model is better than the Markov model in isolating long-term implications of small but important differences in crucial input data.

Genomic medicine and racial/ethnic health disparities: promises, perils, and the challenges for health care and public health policy.

Scientific and policy debates following new genetic discoveries have been intense and emotional when they have involved questions about the causes of, and solutions for, racial and ethnic health disparities in the United States. The difference in prevalence of diseases, allele frequency and genotype frequency among racial/ethnic groups are well known. The genomic profile for a given disease could have different genetic variants for different racial/ethnic groups. Do these results indicate that we have to consider different genetic tests and different genomic medicine for different racial/ethnic groups? If we do this, what is the impact on ethnic and class disparities in health care services in the United States? Current advances in genetic medicine are very promising; however, we must consider the possible impacts of these findings on health disparities, and how genetic medicine can be extended to everyone, not just those who can pay the often high price. If genomic medicine is to be a valid and reliable technology for all citizens regardless of wealth, race, ethnicity, or other determinants of social disadvantage, public health policymakers have to consider a number of policy issues and implications.

Cost effectiveness of lopinavir/ritonavir tablets compared with atazanavir plus ritonavir in antiretroviral-experienced patients in the UK, France, Italy and Spain.

BACKGROUND AND OBJECTIVE: Selection of antiretroviral therapy (ART) for antiretroviral-experienced patients should involve balancing multiple factors, including clinical efficacy, adverse-event risk, resistance concerns, cost effectiveness and expected budget impact. The efficacy of a regimen and its durability, as demonstrated in controlled clinical trials, must be considered in the light of short- and long-term economic impacts on the healthcare system. These impacts may vary based on drug costs, costs of reported adverse effects, the regimen's likelihood of contributing to viral resistance to second-line therapies and the marginal cost differences between other healthcare resources used over a patient's lifetime. Risk of coronary heart disease (CHD) may be of concern in the selection of ART, because differences in CHD risk factors have been reported for different regimens, and heart disease is both a deadly and costly condition. This study set out to estimate the long-term combined effects of HIV disease and antiretroviral-related risk for CHD on quality-adjusted survival and healthcare costs for antiretroviral-experienced patients in the UK, Spain, Italy and France. METHODS: A previously validated Markov model was updated with 2006 cost estimates for each of the four countries and supplemented with the Framingham CHD risk equation. In the model, the average patient was male, aged 37 years, with a baseline 10-year CHD risk of 4.6%. Patients started with either lopinavir/ritonavir (LPV/r) or ritonavir-boosted atazanavir (ATV+RTV) as the protease inhibitor (PI). Clinical trial results, local drug costs and AIDS and CHD cost estimates were used to estimate the differences between these two therapies. RESULTS: There was a significant advantage using LPV/r over ATV+RTV, which varied depending on the country's cost structure and assumptions related to drug efficacy. There was a comparative benefit for experienced patients in quality-adjusted life-months (QALM) of 4.6 (the net gain after subtracting quality-adjusted life-years [QALYs] lost owing to CHD risk). In addition, there were 5- and 10-year overall cost savings of between euro947 and euro6594 per patient after 5 years, and an impact ranging from a cost increase of euro308 (for France) to a cost saving of euro7388 (for Spain) at year 10. The lifetime incremental cost-effectiveness ratios ranged from dominant for Spain to euro11 856/QALY for Italy. CONCLUSION: LPV/r was a highly cost-effective regimen relative to ATV+RTV for the treatment of HIV for each of the four countries examined in this study. The effect of LPV/r on long-term CHD risk was minimal compared with the increased risk of AIDS/death projected for a less efficacious PI-based regimen. The cost of lipid-lowering drugs and treatment for CHD was insignificant compared with the overall cost savings from LPV/r therapy. The choice of regimen for antiretroviral-experienced patients should be based on a regimen's expected efficacy and durability for countries with similar cost structure to those examined here.

Cost effectiveness of lopinavir/ritonavir compared with atazanavir plus ritonavir in antiretroviral-experienced patients in the US.

OBJECTIVE: To estimate the cost effectiveness and long-term combined effects of HIV disease and antiretroviral (ARV) therapy-related risk for coronary heart disease (CHD) on quality-adjusted survival and healthcare costs for ARV-experienced patients. METHODS: A previously validated Markov model was updated and supplemented with the Framingham CHD risk equation. The representative patient in the model was male, aged 37 years and had a baseline 10-year CHD risk of 4.6%. Patients started with either lopinavir/ritonavir (LPV/r) or ritonavir-boosted atazanavir (ATV+RTV) as the protease inhibitor (PI). The proportions of patients with viral suppression below 400 and 50 copies/mL, respectively, at week 48 reported in clinical trials were used to estimate the differences between these two therapies. The daily ARV costs were $US 24.60 for LPV/r capsules (2005 costs) and $US 26.54 for LPV/r tablets (2006 costs), $US 29.76 for ATV and $US 8.57 for ritonavir (2005 costs). Costs of other ARV drugs were taken from average wholesale drug reports for 2005. The cost of AIDS events was estimated from Medicaid billing databases and reflected a medical care system perspective and 2005 treatment costs. Cost-effectiveness calculations assumed a lifetime time horizon. The effects of different model assumptions were tested in a multiway sensitivity analysis by combining extreme values of parameters. RESULTS: The model estimated a clinical and economic advantage to using LPV/r over ATV+RTV, which varied depending upon the use of LPV/r capsules or tablets. Using LPV/r capsules was comparatively beneficial for ARV-experienced patients in quality-adjusted life-months (QALMs) of 4.6 (corrected for differences in CHD risk) compared with ATV+RTV. In addition, there were 5- and 10-year overall per-patient cost savings of $US 17,995 and $US 21,298, respectively. Estimates for the LPV/r tablet formulation approved in 2005 (assuming similar efficacy) improved cost savings over 5- and 10-year periods to $US 19,598 and $US 23,126 per patient, respectively, because of a drug price differential. Sensitivity analysis tested numerous assumptions about the model cost and efficacy parameters and found that the results were robust to most changes. Model limitations were the uncertainty associated with the model parameters used. CONCLUSION: LPV/r appears to be a highly cost-effective regimen relative to ATV+RTV for the treatment of HIV. The long-term CHD risk associated with LPV/r was minimal compared with the increased risk of AIDS/death and costs projected for a less efficacious PI-based regimen.