Margaret Brandeau

All Publications

• Balancing Immunological Benefits and Cardiovascular Risks of Antiretroviral Therapy: When Is Immediate Treatment Optimal? CLINICAL INFECTIOUS DISEASES Negoescu, D. M., Owens, D. K., Brandeau, M. L., Bendavid, E. 2012; 55 (10): 1392-1399

  Abstract

  We developed a mathematical model to identify the timing of antiretroviral therapy (ART) initiation that optimizes patient outcomes as a function of patient CD4 count, age, cardiac mortality risk, sex, and personal preferences. Our goal was to find the conditions that maximize patient quality-adjusted life expectancy (QALE) in the context of our model. Under the assumption that ART confers disease progression and mortality benefits at any CD4 count, immediate treatment initiation yields the greatest remaining QALE for young patients under most circumstances. The timing of ART initiation depends on the magnitude of benefit from ART at high CD4 counts, the magnitude of increases in cardiac risk, and patients' preferences. If ART reduces HIV progression at high CD4 counts, immediate ART is preferable for most newly infected individuals <35 years even if ART doubles age- and sex-specific cardiac risk.

  View details for DOI 10.1093/cid/cis731

  View details for Web of Science ID 000310374600023

  View details for PubMedID 22942203

• Cost Effectiveness of Screening Strategies for Early Identification of HIV and HCV Infection in Injection Drug Users PLOS ONE Cipriano, L. E., Zaric, G. S., Holodniy, M., Bendavid, E., Owens, D. K., Brandeau, M. L. 2012; 7 (9)

  Abstract

  To estimate the cost, effectiveness, and cost effectiveness of HIV and HCV screening of injection drug users (IDUs) in opioid replacement therapy (ORT).Dynamic compartmental model of HIV and HCV in a population of IDUs and non-IDUs for a representative U.S. urban center with 2.5 million adults (age 15-59).We considered strategies of screening individuals in ORT for HIV, HCV, or both infections by antibody or antibody and viral RNA testing. We evaluated one-time and repeat screening at intervals from annually to once every 3 months. We calculated the number of HIV and HCV infections, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs).Adding HIV and HCV viral RNA testing to antibody testing averts 14.8-30.3 HIV and 3.7-7.7 HCV infections in a screened population of 26,100 IDUs entering ORT over 20 years, depending on screening frequency. Screening for HIV antibodies every 6 months costs $30,700/QALY gained. Screening for HIV antibodies and viral RNA every 6 months has an ICER of $65,900/QALY gained. Strategies including HCV testing have ICERs exceeding $100,000/QALY gained unless awareness of HCV-infection status results in a substantial reduction in needle-sharing behavior.Although annual screening for antibodies to HIV and HCV is modestly cost effective compared to no screening, more frequent screening for HIV provides additional benefit at less cost. Screening individuals in ORT every 3-6 months for HIV infection using both antibody and viral RNA technologies and initiating ART for acute HIV infection appears cost effective.

  View details for DOI 10.1371/journal.pone.0045176

  View details for Web of Science ID 000311313900091

  View details for PubMedID 23028828

• Are organic foods safer or healthier than conventional alternatives?: a systematic review. Annals of internal medicine Smith-Spangler, C., Brandeau, M. L., Hunter, G. E., Bavinger, J. C., Pearson, M., Eschbach, P. J., Sundaram, V., Liu, H., Schirmer, P., Stave, C., Olkin, I., Bravata, D. M. 2012; 157 (5): 348-366

  Abstract

  The health benefits of organic foods are unclear.To review evidence comparing the health effects of organic and conventional foods.MEDLINE (January 1966 to May 2011), EMBASE, CAB Direct, Agricola, TOXNET, Cochrane Library (January 1966 to May 2009), and bibliographies of retrieved articles.English-language reports of comparisons of organically and conventionally grown food or of populations consuming these foods.2 independent investigators extracted data on methods, health outcomes, and nutrient and contaminant levels.17 studies in humans and 223 studies of nutrient and contaminant levels in foods met inclusion criteria. Only 3 of the human studies examined clinical outcomes, finding no significant differences between populations by food type for allergic outcomes (eczema, wheeze, atopic sensitization) or symptomatic Campylobacter infection. Two studies reported significantly lower urinary pesticide levels among children consuming organic versus conventional diets, but studies of biomarker and nutrient levels in serum, urine, breast milk, and semen in adults did not identify clinically meaningful differences. All estimates of differences in nutrient and contaminant levels in foods were highly heterogeneous except for the estimate for phosphorus; phosphorus levels were significantly higher than in conventional produce, although this difference is not clinically significant. The risk for contamination with detectable pesticide residues was lower among organic than conventional produce (risk difference, 30% [CI, -37% to -23%]), but differences in risk for exceeding maximum allowed limits were small. Escherichia coli contamination risk did not differ between organic and conventional produce. Bacterial contamination of retail chicken and pork was common but unrelated to farming method. However, the risk for isolating bacteria resistant to 3 or more antibiotics was higher in conventional than in organic chicken and pork (risk difference, 33% [CI, 21% to 45%]).Studies were heterogeneous and limited in number, and publication bias may be present.The published literature lacks strong evidence that organic foods are significantly more nutritious than conventional foods. Consumption of organic foods may reduce exposure to pesticide residues and antibiotic-resistant bacteria.None.

  View details for DOI 10.7326/0003-4819-157-5-201209040-00007

  View details for PubMedID 22944875

• The Cost-Effectiveness of Preexposure Prophylaxis for HIV Prevention in the United States in Men Who Have Sex With Men ANNALS OF INTERNAL MEDICINE Juusola, J. L., Brandeau, M. L., Owens, D. K., Bendavid, E. 2012; 156 (8): 541-U144

  Abstract

  A recent randomized, controlled trial showed that daily oral preexposure chemoprophylaxis (PrEP) was effective for HIV prevention in men who have sex with men (MSM). The Centers for Disease Control and Prevention recently provided interim guidance for PrEP in MSM at high risk for HIV. Previous studies did not reach a consistent estimate of its cost-effectiveness.To estimate the effectiveness and cost-effectiveness of PrEP in MSM in the United States.Dynamic model of HIV transmission and progression combined with a detailed economic analysis.Published literature.MSM aged 13 to 64 years in the United States.Lifetime.Societal.PrEP was evaluated in both the general MSM population and in high-risk MSM and was assumed to reduce infection risk by 44% on the basis of clinical trial results.New HIV infections, discounted quality-adjusted life-years (QALYs) and costs, and incremental cost-effectiveness ratios.Initiating PrEP in 20% of MSM in the United States would reduce new HIV infections by an estimated 13% and result in a gain of 550,166 QALYs over 20 years at a cost of $172,091 per QALY gained. Initiating PrEP in a larger proportion of MSM would prevent more infections but at an increasing cost per QALY gained (up to $216,480 if all MSM receive PrEP). Preexposure chemoprophylaxis in only high-risk MSM can improve cost-effectiveness. For MSM with an average of 5 partners per year, PrEP costs approximately $50,000 per QALY gained. Providing PrEP to all high-risk MSM for 20 years would cost $75 billion more in health care-related costs than the status quo and $600,000 per HIV infection prevented, compared with incremental costs of $95 billion and $2 million per infection prevented for 20% coverage of all MSM.PrEP in the general MSM population would cost less than $100,000 per QALY gained if the daily cost of antiretroviral drugs for PrEP was less than $15 or if PrEP efficacy was greater than 75%.When examining PrEP in high-risk MSM, the investigators did not model a mix of low- and high-risk MSM because of lack of data on mixing patterns.PrEP in the general MSM population could prevent a substantial number of HIV infections, but it is expensive. Use in high-risk MSM compares favorably with other interventions that are considered cost-effective but could result in annual PrEP expenditures of more than $4 billion.National Institute on Drug Abuse, Department of Veterans Affairs, and National Institute of Allergy and Infectious Diseases.

  View details for DOI 10.1059/0003-4819-156-8-201204170-00001

  View details for Web of Science ID 000303151800013

  View details for PubMedID 22508731

• Optimal link removal for epidemic mitigation: A two-way partitioning approach MATHEMATICAL BIOSCIENCES Enns, E. A., Mounzer, J. J., Brandeau, M. L. 2012; 235 (2): 138-147

  Abstract

  The structure of the contact network through which a disease spreads may influence the optimal use of resources for epidemic control. In this work, we explore how to minimize the spread of infection via quarantining with limited resources. In particular, we examine which links should be removed from the contact network, given a constraint on the number of removable links, such that the number of nodes which are no longer at risk for infection is maximized. We show how this problem can be posed as a non-convex quadratically constrained quadratic program (QCQP), and we use this formulation to derive a link removal algorithm. The performance of our QCQP-based algorithm is validated on small Erd?s-Renyi and small-world random graphs, and then tested on larger, more realistic networks, including a real-world network of injection drug use. We show that our approach achieves near optimal performance and out-performs other intuitive link removal algorithms, such as removing links in order of edge centrality.

  View details for DOI 10.1016/j.mbs.2011.11.006

  View details for Web of Science ID 000301020300003

  View details for PubMedID 22115862

• Decision Making for HIV Prevention and Treatment Scale up: Bridging the Gap between Theory and Practice MEDICAL DECISION MAKING Alistar, S. S., Brandeau, M. L. 2012; 32 (1): 105-117

  Abstract

  Effectively controlling the HIV epidemic will require efficient use of limited resources. Despite ambitious global goals for HIV prevention and treatment scale up, few comprehensive practical tools exist to inform such decisions.We briefly summarize modeling approaches for resource allocation for epidemic control, and discuss the practical limitations of these models. We describe typical challenges of HIV resource allocation in practice and some of the tools used by decision makers. We identify the characteristics needed in a model that can effectively support planners in decision making about HIV prevention and treatment scale up.An effective model to support HIV scale-up decisions will be flexible, with capability for parameter customization and incorporation of uncertainty. Such a model needs certain key technical features: it must capture epidemic effects; account for how intervention effectiveness depends on the target population and the level of scale up; capture benefit and cost differentials for packages of interventions versus single interventions, including both treatment and prevention interventions; incorporate key constraints on potential funding allocations; identify optimal or near-optimal solutions; and estimate the impact of HIV interventions on the health care system and the resulting resource needs. Additionally, an effective model needs a user-friendly design and structure, ease of calibration and validation, and accessibility to decision makers in all settings.Resource allocation theory can make a significant contribution to decision making about HIV prevention and treatment scale up. What remains now is to develop models that can bridge the gap between theory and practice.

  View details for DOI 10.1177/0272989X10391808

  View details for Web of Science ID 000299701100014

  View details for PubMedID 21191118

• Assessing effectiveness and cost-effectiveness of concurrency reduction for HIV prevention INTERNATIONAL JOURNAL OF STD & AIDS Enns, E. A., Brandeau, M. L., Igeme, T. K., Bendavid, E. 2011; 22 (10): 558-567

  Abstract

  We estimated the effectiveness and cost-effectiveness of changes in concurrent sexual partnerships in reducing the spread of HIV in sub-Saharan Africa. Using data from Swaziland, Tanzania, Uganda and Zambia, we estimated country-specific concurrency behaviour from sexual behaviour survey data on the number of partners in the past 12 months, and we developed a network model to compare the impact of three behaviour changes on the HIV epidemic: (1) changes in concurrent partnership patterns to strict monogamy; (2) partnership reduction among those with the greatest number of partners; and (3) partnership reduction among all individuals. We estimated the number of new HIV infections over 10 years and the cost per infection averted. Given our assumptions and model structure, we find that reducing concurrency among high-risk individuals averts the most infections and increasing monogamy the least (11.7% versus 8.7% reduction in new infections, on average, for a 10% reduction in concurrent partnerships). A campaign that costs US$1 per person annually is likely cost-saving if it reduces concurrency by 9% on average, given our baseline estimates of concurrency. In sensitivity analysis, the rank ordering of behaviour change scenarios was unaffected by potential over-estimation of concurrency, though the number of infections averted decreased and the cost per HIV infection averted increased. Concurrency reduction programmes may be effective and cost-effective in reducing HIV incidence in sub-Saharan Africa if they can achieve even modest impacts at similar costs to past mass media campaigns in the region. Reduced concurrency among high-risk individuals appears to be most effective in reducing HIV incidence, but concurrency reduction in other risk groups may yield nearly as much benefit.

  View details for DOI 10.1258/ijsa.2011.010322

  View details for Web of Science ID 000296991200004

  View details for PubMedID 21998175

• Doing Good with Good OR: Supporting Cost-Effective Hepatitis B Interventions INTERFACES Hutton, D. W., Brandeau, M. L., So, S. K. 2011; 41 (3): 289-300

  Abstract

  In an era of limited healthcare budgets, mathematical models can be useful tools to identify cost-effective programs and to support policymakers in informed decision making. This paper reports results of our work carried out over several years with the Asian Liver Center at Stanford University, a nonprofit outreach and advocacy organization that is an international leader in the fight against hepatitis B and liver cancer. Hepatitis B is a vaccine-preventable viral disease that, if untreated, can lead to death from cirrhosis and liver cancer. Infection with hepatitis B is a major public health problem, particularly in Asian populations. We used new combinations of decision analysis and Markov models to analyze the cost-effectiveness of several interventions to combat hepatitis B in the United States and China. The results of our OR-based analyses have helped change United States public health policy on hepatitis B screening for millions of people and have helped encourage policymakers in China to enact legislation to provide free catch-up vaccination for hundreds of millions of children. These policies are an important step in eliminating health disparities, reducing discrimination, and ensuring that millions of people who need it can now receive hepatitis B vaccination or lifesaving treatment.

  View details for DOI 10.1287/inte.1100.0511

  View details for Web of Science ID 000292246700007

  View details for PubMedID 21760650

• Effectiveness and Cost Effectiveness of Expanding Harm Reduction and Antiretroviral Therapy in a Mixed HIV Epidemic: A Modeling Analysis for Ukraine PLOS MEDICINE Alistar, S. S., Owens, D. K., Brandeau, M. L. 2011; 8 (3)

  Abstract

  Injection drug use (IDU) and heterosexual virus transmission both contribute to the growing mixed HIV epidemics in Eastern Europe and Central Asia. In Ukraine-chosen in this study as a representative country-IDU-related risk behaviors cause half of new infections, but few injection drug users (IDUs) receive methadone substitution therapy. Only 10% of eligible individuals receive antiretroviral therapy (ART). The appropriate resource allocation between these programs has not been studied. We estimated the effectiveness and cost-effectiveness of strategies for expanding methadone substitution therapy programs and ART in mixed HIV epidemics, using Ukraine as a case study.We developed a dynamic compartmental model of the HIV epidemic in a population of non-IDUs, IDUs using opiates, and IDUs on methadone substitution therapy, stratified by HIV status, and populated it with data from the Ukraine. We considered interventions expanding methadone substitution therapy, increasing access to ART, or both. We measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, infections averted, and incremental cost-effectiveness. Without incremental interventions, HIV prevalence reached 67.2% (IDUs) and 0.88% (non-IDUs) after 20 years. Offering methadone substitution therapy to 25% of IDUs reduced prevalence most effectively (to 53.1% IDUs, 0.80% non-IDUs), and was most cost-effective, averting 4,700 infections and adding 76,000 QALYs compared with no intervention at US$530/QALY gained. Expanding both ART (80% coverage of those eligible for ART according to WHO criteria) and methadone substitution therapy (25% coverage) was the next most cost-effective strategy, adding 105,000 QALYs at US$1,120/QALY gained versus the methadone substitution therapy-only strategy and averting 8,300 infections versus no intervention. Expanding only ART (80% coverage) added 38,000 QALYs at US$2,240/QALY gained versus the methadone substitution therapy-only strategy, and averted 4,080 infections versus no intervention. Offering ART to 80% of non-IDUs eligible for treatment by WHO criteria, but only 10% of IDUs, averted only 1,800 infections versus no intervention and was not cost effective.Methadone substitution therapy is a highly cost-effective option for the growing mixed HIV epidemic in Ukraine. A strategy that expands both methadone substitution therapy and ART to high levels is the most effective intervention, and is very cost effective by WHO criteria. When expanding ART, access to methadone substitution therapy provides additional benefit in infections averted. Our findings are potentially relevant to other settings with mixed HIV epidemics. Please see later in the article for the Editors' Summary.

  View details for DOI 10.1371/journal.pmed.1000423

  View details for Web of Science ID 000288945200004

  View details for PubMedID 21390264