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1.  The Cost-effectiveness of Rapid HIV Testing in Substance Abuse Treatment: Results of a Randomized Trial* 
Drug and alcohol dependence  2012;128(1-2):90-97.
The President’s National HIV/AIDS Strategy calls for coupling HIV screening and prevention services with substance abuse treatment programs. Fewer than half of US community-based substance abuse treatment programs make HIV testing available on-site or through referral.
We measured the cost-effectiveness of three HIV testing strategies evaluated in a randomized trial conducted in 12 community-based substance abuse treatment programs in 2009: off-site testing referral, on-site rapid testing with information only, on-site rapid testing with risk reduction counseling. Data from the trial included patient demographics, prior testing history, test acceptance and receipt of results, undiagnosed HIV prevalence (0.4%) and program costs. The Cost Effectiveness of Preventing AIDS Complications (CEPAC) computer simulation model was used to project life expectancy, lifetime costs, and quality-adjusted life years (QALYs) for HIV-infected individuals. Incremental cost-effectiveness ratios (2009 US $/QALY) were calculated after adding costs of testing HIV-uninfected individuals; costs and QALYs were discounted at 3% annually.
Referral for off-site testing is less efficient (dominated) compared to offering on-site testing with information only. The cost-effectiveness ratio for on-site testing with information is $60,300/QALY in the base case, or $76,300/QALY with 0.1% undiagnosed HIV prevalence. HIV risk-reduction counseling costs $36 per person more without additional benefit.
A strategy of on-site rapid HIV testing offer with information only in substance abuse treatment programs increases life expectancy at a cost-effectiveness ratio <$100,000/QALY. Policymakers and substance abuse treatment leaders should seek funding to implement on-site rapid HIV testing in substance abuse treatment programs for those not recently tested.
PMCID: PMC3546145  PMID: 22971593
Rapid HIV testing; substance use; cost-effectiveness
2.  Mobile HIV Screening in Cape Town, South Africa: Clinical Impact, Cost and Cost-Effectiveness 
PLoS ONE  2014;9(1):e85197.
Mobile HIV screening may facilitate early HIV diagnosis. Our objective was to examine the cost-effectiveness of adding a mobile screening unit to current medical facility-based HIV testing in Cape Town, South Africa.
Methods and Findings
We used the Cost Effectiveness of Preventing AIDS Complications International (CEPAC-I) computer simulation model to evaluate two HIV screening strategies in Cape Town: 1) medical facility-based testing (the current standard of care) and 2) addition of a mobile HIV-testing unit intervention in the same community. Baseline input parameters were derived from a Cape Town-based mobile unit that tested 18,870 individuals over 2 years: prevalence of previously undiagnosed HIV (6.6%), mean CD4 count at diagnosis (males 423/µL, females 516/µL), CD4 count-dependent linkage to care rates (males 31%–58%, females 49%–58%), mobile unit intervention cost (includes acquisition, operation and HIV test costs, $29.30 per negative result and $31.30 per positive result). We conducted extensive sensitivity analyses to evaluate input uncertainty. Model outcomes included site of HIV diagnosis, life expectancy, medical costs, and the incremental cost-effectiveness ratio (ICER) of the intervention compared to medical facility-based testing. We considered the intervention to be “very cost-effective” when the ICER was less than South Africa's annual per capita Gross Domestic Product (GDP) ($8,200 in 2012). We projected that, with medical facility-based testing, the discounted (undiscounted) HIV-infected population life expectancy was 132.2 (197.7) months; this increased to 140.7 (211.7) months with the addition of the mobile unit. The ICER for the mobile unit was $2,400/year of life saved (YLS). Results were most sensitive to the previously undiagnosed HIV prevalence, linkage to care rates, and frequency of HIV testing at medical facilities.
The addition of mobile HIV screening to current testing programs can improve survival and be very cost-effective in South Africa and other resource-limited settings, and should be a priority.
PMCID: PMC3898963  PMID: 24465503
3.  Routine HIV Screening in Portugal: Clinical Impact and Cost-Effectiveness 
PLoS ONE  2013;8(12):e84173.
To compare the clinical outcomes and cost-effectiveness of routine HIV screening in Portugal to the current practice of targeted and on-demand screening.
We used Portuguese national clinical and economic data to conduct a model-based assessment.
We compared current HIV detection practices to strategies of increasingly frequent routine HIV screening in Portuguese adults aged 18-69. We considered several subpopulations and geographic regions with varying levels of undetected HIV prevalence and incidence. Baseline inputs for the national case included undiagnosed HIV prevalence 0.16%, annual incidence 0.03%, mean population age 43 years, mean CD4 count at care initiation 292 cells/μL, 63% HIV test acceptance, 78% linkage to care, and HIV rapid test cost €6 under the proposed routine screening program. Outcomes included quality-adjusted survival, secondary HIV transmission, cost, and incremental cost-effectiveness.
One-time national HIV screening increased HIV-infected survival from 164.09 quality-adjusted life months (QALMs) to 166.83 QALMs compared to current practice and had an incremental cost-effectiveness ratio (ICER) of €28,000 per quality-adjusted life year (QALY). Screening more frequently in higher-risk groups was cost-effective: for example screening annually in men who have sex with men or screening every three years in regions with higher incidence and prevalence produced ICERs of €21,000/QALY and €34,000/QALY, respectively.
One-time HIV screening in the Portuguese national population will increase survival and is cost-effective by international standards. More frequent screening in higher-risk regions and subpopulations is also justified. Given Portugal’s challenging economic priorities, we recommend prioritizing screening in higher-risk populations and geographic settings.
PMCID: PMC3867470  PMID: 24367639
4.  The Survival Benefits of Antiretroviral Therapy in South Africa 
The Journal of Infectious Diseases  2013;209(4):491-499.
Background. We sought to quantify the survival benefits attributable to antiretroviral therapy (ART) in South Africa since 2004.
Methods. We used the Cost-Effectiveness of Preventing AIDS Complications–International model (CEPAC) to simulate 8 cohorts of human immunodeficiency virus (HIV)–infected patients initiating ART each year during 2004–2011. Model inputs included cohort-specific mean CD4+ T-cell count at ART initiation (112–178 cells/µL), 24-week ART suppressive efficacy (78%), second-line ART availability (2.4% of ART recipients), and cohort-specific 36-month retention rate (55%–71%). CEPAC simulated survival twice for each cohort, once with and once without ART. The sum of the products of per capita survival differences and the total numbers of persons initiating ART for each cohort yielded the total survival benefits.
Results. Lifetime per capita survival benefits ranged from 9.3 to 10.2 life-years across the 8 cohorts. Total estimated population lifetime survival benefit for all persons starting ART during 2004–2011 was 21.7 million life-years, of which 2.8 million life-years (12.7%) had been realized by December 2012. By 2030, benefits reached 17.9 million life-years under current policies, 21.7 million life-years with universal second-line ART, 23.3 million life-years with increased linkage to care of eligible untreated patients, and 28.0 million life-years with both linkage to care and universal second-line ART.
Conclusions. We found dramatic past and potential future survival benefits attributable to ART, justifying international support of ART rollout in South Africa.
PMCID: PMC3903379  PMID: 24307741
HIV; South Africa; highly active antiretroviral therapy
5.  Home HIV Testing: Good News but Not a Game Changer 
Annals of internal medicine  2012;157(10):744-746.
PMCID: PMC3661188  PMID: 23044643
6.  Economic savings versus health losses: The cost-effectiveness of generic antiretroviral therapy in the United States 
Annals of internal medicine  2013;158(2):84-92.
US HIV treatment guidelines recommend branded once-daily, one-pill efavirenz/emtricitabine/tenofovir as preferred first-line antiretroviral treatment (ART). With the anticipated approval of generic efavirenz in 2012 in the US, the cost of a once-daily, three-pill alternative (generic efavirenz, generic lamivudine, tenofovir) will decrease, but adherence and virologic suppression may be reduced.
To assess the clinical impact, costs, and cost-effectiveness of the generic-based three-pill regimen compared to the branded, co-formulated regimen. To project the potential national savings in the first year of a switch to generic-based ART.
Mathematical simulation of HIV disease.
Data Sources
Published data from US clinical trials and observational cohorts.
Target Population
HIV-infected patients eligible to start on or switch to an efavirenz-based generic ART regimen.
Time Horizon
Lifetime, One-year
US health system
No ART (for comparison), Three-pill Generic ART, and Branded ART
Outcome Measures
Quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios (ICER, $/quality-adjusted life expectancy [QALY]).
Results of Base-Case Analysis
Compared to No ART, Generic ART has an ICER of $21,100/QALY. Compared to Generic ART, Branded ART increases lifetime costs by $42,500, and per-person survival gains by 0.37 QALYs, for an ICER of $114,800/QALY. Estimated first-year savings, if all eligible US patients start on or switch to Generic ART, are $920 million.
Results of Sensitivity Analysis
Most plausible assumptions about Generic ART efficacy and costs lead to Branded ART ICERs >$100,000/QALY.
The efficacy and price reduction associated with generics are unknown; estimates are intended to be conservative.
Compared to a slightly less effective generic-based regimen, the cost-effectiveness of first-line Branded ART exceeds $100,000/QALY. Generic-based ART in the US could yield substantial budgetary savings to HIV programs.
PMCID: PMC3664029  PMID: 23318310
7.  The Cost-effectiveness of Pre-Exposure Prophylaxis for HIV Infection in South African Women 
As a long-term strategy to decrease HIV acquisition in South African women, pre-exposure prophylaxis is both effective, reducing lifetime risk of infection to 27%, and cost-effective, with an incremental cost-effectiveness ratio of $2700 per years of life saved.
Background. Recent trials report the short-term efficacy of tenofovir-based pre-exposure prophylaxis (PrEP) for prevention of human immunodeficiency virus (HIV) infection. PrEP’s long-term impact on patient outcomes, population-level transmission, and cost-effectiveness remains unknown.
Methods. We linked data from recent trials to a computer model of HIV acquisition, screening, and care to project lifetime HIV risk, life expectancy (LE), costs, and cost-effectiveness, using 2 PrEP-related strategies among heterosexual South African women: (1) women receiving no PrEP and (2) women not receiving PrEP (a tenofovir-based vaginal microbicide). We used a South African clinical cohort and published data to estimate population demographic characteristics, age-adjusted incidence of HIV infection, and HIV natural history and treatment parameters. Baseline PrEP efficacy (percentage reduction in HIV transmission) was 39% at a monthly cost of $5 per woman. Alternative parameter values were examined in sensitivity analyses.
Results. Among South African women, PrEP reduced mean lifetime HIV risk from 40% to 27% and increased population discounted (undiscounted) LE from 22.51 (41.66) to 23.48 (44.48) years. Lifetime costs of care increased from $7280 to $9890 per woman, resulting in an incremental cost-effectiveness ratio of $2700/year of life saved, and may, under optimistic assumptions, achieve cost savings. Under baseline HIV infection incidence assumptions, PrEP was not cost saving, even assuming an efficacy >60% and a cost <$1. At an HIV infection incidence of 9.1%/year, PrEP achieved cost savings at efficacies ≥50%.
Conclusions. PrEP in South African women is very cost-effective by South African standards, conferring excellent value under virtually all plausible data scenarios. Although optimistic assumptions would be required to achieve cost savings, these represent important benchmarks for future PrEP study design.
PMCID: PMC3334365  PMID: 22474224
8.  Placing a Price on Medical Device Innovation: The Example of Total Knee Arthroplasty 
PLoS ONE  2013;8(5):e62709.
Total knee arthroplasty (TKA) is common, effective, and cost-effective. Innovative implants promising reduced long-term failure at increased cost are under continual development. We sought to define the implant cost and performance thresholds under which innovative TKA implants are cost-effective.
We performed a cost-effectiveness analysis using a validated, published computer simulation model of knee osteoarthritis. Model inputs were derived using published literature, Medicare claims, and National Health and Nutrition Examination Survey data. We compared projected TKA implant survival, quality-adjusted life expectancy (QALE), lifetime costs, and cost-effectiveness (incremental cost-effectiveness ratios or ICERs) of standard versus innovative TKA implants. We assumed innovative implants offered 5–70% decreased long-term TKA failure rates at costs 20–400% increased above standard implants. We examined the impact of patient age, comorbidity, and potential increases in short-term failure on innovative implant cost-effectiveness.
Implants offering ≥50% decrease in long-term TKA failure at ≤50% increased cost offered ICERs <$100,000 regardless of age or baseline comorbidity. An implant offering a 20% decrease in long-term failure at 50% increased cost provided ICERs <$150,000 per QALY gained only among healthy 50–59-year-olds. Increasing short-term failure, consistent with recent device failures, reduced cost-effectiveness across all groups. Increasing the baseline likelihood of long-term TKA failure among younger, healthier and more active individuals further enhanced innovative implant cost-effectiveness among younger patients.
Innovative implants must decrease actual TKA failure, not just radiographic wear, by 50–55% or more over standard implants to be broadly cost-effective. Comorbidity and remaining life span significantly affect innovative implant cost-effectiveness and should be considered in the development, approval and implementation of novel technologies, particularly in orthopedics. Model-based evaluations such as this offer valuable, unique insights for evaluating technological innovation in medical devices.
PMCID: PMC3646021  PMID: 23671626
9.  Impact of Program Scale and Indirect Effects on the Cost-Effectiveness of Vaccination Programs 
PMCID: PMC3570235  PMID: 22472916
scale dependency; herd protection; epidemiological model; resource allocation
11.  Predicting the Impact of a Partially Effective HIV Vaccine and Subsequent Risk Behavior Change on the Heterosexual HIV Epidemic in Low- and Middle-Income Countries A South African Example 
We developed a mathematical model to simulate the impact of various partially effective preventive HIV vaccination scenarios in a population at high risk for heterosexually transmitted HIV. We considered an adult population defined by gender (male/female), disease stage (HIV-negative, HIV-positive, AIDS, and death), and vaccination status (unvaccinated/vaccinated) in Soweto, South Africa. Input data included initial HIV prevalence of 20% (women) and 12% (men), vaccination coverage of 75%, and exclusive male negotiation of condom use. We explored how changes in vaccine efficacy and post-vaccination condom use would affect HIV prevalence and total HIV infections prevented over a 10-year period. In the base-case scenario, a 40% effective HIV vaccine would avert 61,000 infections and reduce future HIV prevalence from 20% to 13%. A 25% increase (or decrease) in condom use among vaccinated individuals would instead avert 75,000 (or only 46,000) infections and reduce the HIV prevalence to 12% (or only 15%). Furthermore, certain combinations of increased risk behavior and vaccines with <43% efficacy could worsen the epidemic. Even modestly effective HIV vaccines can confer enormous benefits in terms of HIV infections averted and decreased HIV prevalence. However, programs to reduce risk behavior may be important components of successful vaccination campaigns.
PMCID: PMC3570247  PMID: 17589368
AIDS vaccines; mathematical models; sexual behavior; heterosexual transmission; Africa; condoms; models/projections
Health economics  2008;17(8):927-946.
Reduced crime provides a key benefit associated with substance abuse treatment (SAT). Armed robbery is an especially costly and frequent crime committed by some drug-involved offenders. Many studies employ valuation methods that understate the true costs of robbery, and thus the true social benefits of SAT-related robbery reduction. At the same time, regression to the mean and self-report bias may lead pre–post comparisons to overstate crime reductions associated with SAT.
Using 1992–1997 data from the National Treatment Improvement Evaluation Study (NTIES), we examined pre–post differences in self-reported robbery among clients in five residential and outpatient SAT modalities. Fixed-effect negative binomial regression was used to examine incidence rate reductions (IRR) in armed robbery. Published data on willingness to pay to avoid robbery were used to determine the social valuation of these effects. Differences in IRR across SAT modalities were explored to bound potential biases.
All SAT modalities were associated with large and statistically significant reductions in robbery. The average number of self-reported robberies declined from 0.83/client/year pre-entry to 0.12/client/year following SAT (p < 0.001). Under worst-case assumptions, monetized valuations of reductions in armed robbery associated with outpatient methadone and residential SAT exceeded economic costs of these interventions. Conventional wisdom posits the economic benefits of SAT. We find that SAT is even more beneficial than is commonly assumed.
PMCID: PMC3512566  PMID: 17992708
drug treatment; robbery; contingent valuation; cost-benefit; substance abuse
13.  Modeling the Potential Impact of a Prescription Drug Copayment Increase on the Adult Asthmatic Medicaid Population 
The Commonwealth of Massachusetts increased the copayment for prescription drugs by $1.50 for Medicaid (MassHealth) beneficiaries in 2003. We sought to determine the likely health outcomes and cost shifts attributable to this copayment increase using the example of inhaled corticosteroids (ICS) use among adult asthmatic Medicaid beneficiaries.
We compared the predicted costs and health outcomes projected over a 1-year time horizon with and without the increase in copayment from the perspective of MassHealth, providers, pharmacies, and MassHealth beneficiaries by employing decision analysis simulation model.
In a target population of 17,500 adult asthmatics, increased copayments from 50¢ to $2.00 would result in an additional 646 acute events per year, caused by increased drug nonadherence. Annual combined net savings for the state and federal governments would be $2.10 million. Projected MassHealth savings are attributable to both decreased drug utilization and lower pharmacy reimbursement rates; these more than offset the additional costs of more frequent acute exacerbations. Pharmacies would lose $1.98 million in net revenues, MassHealth beneficiaries would pay an additional $0.28 million, and providers would receive additional $0.16 million.
Over its first year of implementation, increase in the prescription drug copayment is expected to produce more frequent acute exacerbations among asthmatic MassHealth beneficiaries who use ICS and to shift the financial burden from government to other stakeholders.
PMCID: PMC3476042  PMID: 18237365
asthma; copayment; medicaid; prescription drug
14.  Cost-effectiveness of omalizumab in adults with severe asthma: Results from the Asthma Policy Model 
Omalizumab (trade name Xolair) is approved by the US Food and Drug Administration for treatment of moderate-to-severe allergic asthma. Given the high acquisition cost of omalizumab, its role and cost-effectiveness in disease management require definition.
We sought to identify the clinical and economic circumstances under which omalizumab might or might not be a cost-effective option by using a mathematic model.
We merged published data on clinical and economic outcomes (including acute event incidence, frequency/severity of hospitalizations, and health-related quality of life) to project 10-year costs, quality-adjusted life years (QALYs), and cost-effectiveness of treatment with omalizumab in addition to inhaled corticosteroids. Sensitivity analyses were conducted by using input data ranges from a variety of sources (published clinical trials and observational databases).
For patients with baseline acute event rates, omalizumab conferred an additional 1.7 quality-adjusted months at an incremental cost of $131,000 over a 10-year planning horizon, implying a cost-effectiveness ratio of $821,000 per QALY gained. For patients with 5 times the baseline acute event rate, the cost-effectiveness ratio was $491,000 per QALY gained. The projected cost-effectiveness ratio could fall within a range of other programs that are widely considered to be cost-effective if the cost of omalizumab decreases to less than $200.
Omalizumab is not cost-effective for most patients with severe asthma. The projected cost-effectiveness ratios could fall within a favorable range if the cost of omalizumab decreases significantly.
Clinical implications
Based on the high cost of omalizumab, it is especially important that clinicians explore alternative medications for asthma before initiating omalizumab.
PMCID: PMC3476046  PMID: 17904628
Omalizumab; cost-effectiveness; asthma; anti-IgE
15.  The potential impact of an HIV vaccine with rapidly waning protection on the epidemic in Southern Africa: Examining the RV144 trial results 
Vaccine  2011;29(36):6107-6112.
The prime-boost HIV vaccine regimen used in the recent RV144 trial resulted in modest efficacy of 31% over 3.5 years, but was substantially higher in the first year post-vaccination. We sought to explore the potential impact of a vaccine with rapidly waning efficacy in a South African population.
We explored two strategies using a dynamic compartmental epidemic model for heterosexual transmission of HIV: (1) vaccination of a single cohort (30%, 60% or 90% of the initial population), with potential booster vaccinations at 5-year or 2-year intervals over time, and (2) vaccination of the overall population at coverage levels (30%, 60% or 90%) that are constant over time, such that individuals are vaccinated or revaccinated to maintain effective coverage levels, given the rapidly waning protection of the vaccine. We also examined potential changes in post-vaccination condom use.
The single cohort vaccination strategies did not have a substantial impact on HIV prevalence, although without boosters they still prevented 2–6% of the expected infections at 20 years, depending on the population coverage. The 5-year and 2-year booster strategies prevented 8–24% and 17–45% of the expected infections, respectively. The continuous vaccination strategies resulted in more substantial reductions in population HIV prevalence and greater numbers of infections prevented: HIV prevalence at 20 years was reduced from 23% to 8–14% and the number of expected infections was decreased by 34–59%, depending on the population coverage level. Moderate changes in post-vaccination condom use did not substantially affect these outcomes.
An HIV vaccine with partial efficacy and declining protection similar to the RV144 vaccine could prevent a substantial proportion of HIV infections if booster vaccinations were effective and available. Our estimates of the population impact of vaccination would be improved by further understanding of the duration of protection, the effectiveness of booster vaccination, and whether the vaccine efficacy varies between subpopulations at higher and lower risk of exposure.
PMCID: PMC3164284  PMID: 21736912
HIV vaccine; mathematical model; HIV prevention; South Africa; combination prevention
16.  Dengue vector control strategies in an urban setting: an economic modelling assessment 
Lancet  2011;377(9778):1673-1680.
An estimated 2·5 billion people are at risk of dengue. Incidence of dengue is especially high in resource-constrained countries, where control relies mainly on insecticides targeted at larval or adult mosquitoes. We did epidemiological and economic assessments of different vector control strategies.
We developed a dynamic model of dengue transmission that assesses the evolution of insecticide resistance and immunity in the human population, thus allowing for long-term evolutionary and immunological effects of decreased dengue transmission. We measured the dengue health burden in terms of disability-adjusted life-years (DALYs) lost. We did a cost-effectiveness analysis of 43 insecticide-based vector control strategies, including strategies targeted at adult and larval stages, at varying efficacies (high-efficacy [90% mortality], medium-efficacy [60% mortality], and low-efficacy [30% mortality]) and yearly application frequencies (one to six applications). To assess the effect of parameter uncertainty on the results, we did a probabilistic sensitivity analysis and a threshold analysis.
All interventions caused the emergence of insecticide resistance, which, with the loss of herd immunity, will increase the magnitude of future dengue epidemics. In our model, one or more applications of high-efficacy larval control reduced dengue burden for up to 2 years, whereas three or more applications of adult vector control reduced dengue burden for up to 4 years. The incremental cost-effectiveness ratios of the strategies for two high-efficacy adult vector control applications per year was US$615 per DALY saved and for six high-efficacy adult vector control applications per year was $1267 per DALY saved. Sensitivity analysis showed that if the cost of adult control was more than 8·2 times the cost of larval control then all strategies based on adult control became dominated.
Six high-efficacy adult vector control applications per year has a cost-effectiveness ratio that will probably meet WHO's standard for a cost-effective or very cost-effective intervention. Year-round larval control can be counterproductive, exacerbating epidemics in later years because of evolution of insecticide resistance and loss of herd immunity. We suggest the reassessment of vector control policies that are based on larval control only.
The Fulbright Programme, CAPES (Brazilian federal agency for post-graduate education), the Miriam Burnett trust, and the Notsew Orm Sands Foundation.
PMCID: PMC3409589  PMID: 21546076
17.  Scaling Up Circumcision Programs in Southern Africa: The Potential Impact of Gender Disparities and Changes in Condom Use Behaviors on Heterosexual HIV Transmission 
AIDS and behavior  2011;15(5):938-948.
Circumcision significantly reduces female-to-male transmission of HIV infection, but changes in behavior may influence the overall impact on transmission. We sought to explore these effects, particularly for societies where women have less power to negotiate safe sex. We developed a compartmental epidemic model to simulate the population-level impact of various circumcision programs on heterosexual HIV transmission in Soweto. We incorporated gender-specific negotiation of condom use in sexual partnerships and explored post-circumcision changes in condom use. A 5-year prevention program in which only an additional 10% of uncircumcised males undergo circumcision each year, for example, would prevent 13% of the expected new HIV infections over 20 years. Outcomes were sensitive to potential changes in behavior and differed by gender. For Southern Africa, even modest programs offering circumcision would result in significant benefits. Because decreases in male condom use could diminish these benefits, particularly for women, circumcision programs should emphasize risk-reduction counseling.
PMCID: PMC3112296  PMID: 20924783
Male circumcision; Mathematical models; HIV prevention; Africa; Sexual behavior
18.  Simulating school closure policies for cost effective pandemic decision making 
BMC Public Health  2012;12:449.
Around the globe, school closures were used sporadically to mitigate the 2009 H1N1 influenza pandemic. However, such closures can detrimentally impact economic and social life.
Here, we couple a decision analytic approach with a mathematical model of influenza transmission to estimate the impact of school closures in terms of epidemiological and cost effectiveness. Our method assumes that the transmissibility and the severity of the disease are uncertain, and evaluates several closure and reopening strategies that cover a range of thresholds in school-aged prevalence (SAP) and closure durations.
Assuming a willingness to pay per quality adjusted life-year (QALY) threshold equal to the US per capita GDP ($46,000), we found that the cost effectiveness of these strategies is highly dependent on the severity and on a willingness to pay per QALY. For severe pandemics, the preferred strategy couples the earliest closure trigger (0.5% SAP) with the longest duration closure (24 weeks) considered. For milder pandemics, the preferred strategies also involve the earliest closure trigger, but are shorter duration (12 weeks for low transmission rates and variable length for high transmission rates).
These findings highlight the importance of obtaining early estimates of pandemic severity and provide guidance to public health decision-makers for effectively tailoring school closures strategies in response to a newly emergent influenza pandemic.
PMCID: PMC3495022  PMID: 22713694
19.  Projected Survival Gains from Revising State Laws Requiring Written Opt-in Consent for HIV Testing 
Although the Centers for Disease Control and Prevention recommends HIV testing in all settings unless patients refuse (opt-out consent), many state laws require written opt-in consent.
To quantify potential survival gains from passing state laws streamlining HIV testing consent.
We retrieved surveillance data to estimate the current annual HIV diagnosis rate in states with laws requiring written opt-in consent (19.3%). Published data informed the effect of removing that requirement on diagnosis rate (48.5% increase). These parameters then served as input for a model-driven projection of survival based on consent method. Other inputs included undiagnosed HIV prevalence (0.101%); and annual HIV incidence (0.023%).
Hypothetical cohort of adults (>13 years) living in written opt-in states.
Life years gained (LYG).
In the base-case, of the 53,036,383 adult persons living in written opt-in states, 0.66% (350,040) will be infected with HIV. Due to earlier diagnosis, revised consent laws yield 1.5 LYG per HIV-infected person, corresponding to 537,399 LYG among this population. Sensitivity analyses demonstrate that diagnosis rate increases of 24.8-72.3% result in 304,765–724,195 LYG. Net survival gains vanish if the proportion of HIV-infected persons refusing all testing in response to revised laws exceeds 18.2%.
The potential survival gains of increased testing are substantial, suggesting that state laws requiring opt-in HIV testing should be revised.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-011-1637-5) contains supplementary material, which is available to authorized users.
PMCID: PMC3101973  PMID: 21286837
HIV; AIDS; screening; modeling; survival analysis
20.  Impact of Obesity and Knee Osteoarthritis on Morbidity and Mortality in Older Americans 
Annals of Internal Medicine  2011;154(4):217-226.
Obesity and knee osteoarthritis are among the most frequent chronic conditions affecting Americans aged 50 to 84 years.
To estimate quality-adjusted life-years lost due to obesity and knee osteoarthritis and health benefits of reducing obesity prevalence to levels observed a decade ago.
The U.S. Census and obesity data from national data sources were combined with estimated prevalence of symptomatic knee osteoarthritis to assign persons aged 50 to 84 years to 4 subpopulations: nonobese without knee osteoarthritis (reference group), nonobese with knee osteoarthritis, obese without knee osteoarthritis, and obese with knee osteoarthritis. The Osteoarthritis Policy Model, a computer simulation model of knee osteoarthritis and obesity, was used to estimate quality-adjusted life-year losses due to knee osteoarthritis and obesity in comparison with the reference group.
United States.
U.S. population aged 50 to 84 years.
Quality-adjusted life-years lost owing to knee osteoarthritis and obesity.
Estimated total losses of per-person quality-adjusted life-years ranged from 1.857 in nonobese persons with knee osteoarthritis to 3.501 for persons affected by both conditions, resulting in a total of 86.0 million quality-adjusted life-years lost due to obesity, knee osteoarthritis, or both. Quality-adjusted life-years lost due to knee osteoarthritis and/or obesity represent 10% to 25% of the remaining quality-adjusted survival of persons aged 50 to 84 years. Hispanic and black women had disproportionately high losses. Model findings suggested that reversing obesity prevalence to levels seen 10 years ago would avert 178 071 cases of coronary heart disease, 889 872 cases of diabetes, and 111 206 total knee replacements. Such a reduction in obesity would increase the quantity of life by 6 318 030 years and improve life expectancy by 7 812 120 quality-adjusted years in U.S. adults aged 50 to 84 years.
Comorbidity incidences were derived from prevalence estimates on the basis of life expectancy of the general population, potentially resulting in conservative underestimates. Calibration analyses were conducted to ensure comparability of model-based projections and data from external sources.
The number of quality-adjusted life-years lost owing to knee osteoarthritis and obesity seems to be substantial, with black and Hispanic women experiencing disproportionate losses. Reducing mean body mass index to the levels observed a decade ago in this population would yield substantial health benefits.
Primary Funding Source
The National Institutes of Health and the Arthritis Foundation.
PMCID: PMC3260464  PMID: 21320937
21.  The Clinical Impact and Cost-Effectiveness of Routine, Voluntary HIV Screening in South Africa 
Although 900,000 HIV-infected South Africans receive antiretroviral therapy (ART), the majority of South Africans with HIV remain undiagnosed.
We use a published simulation model of HIV case detection and treatment to examine three HIV screening scenarios, in addition to current practice: 1) one-time; 2) every five years; and 3) annually. South African model input data include: 16.9% HIV prevalence, 1.3% annual incidence, 49% test acceptance rate, HIV testing costs of $6.49/patient, and a 47% linkage-to-care rate (including two sequential ART regimens) for identified cases. Outcomes include life expectancy, direct medical costs, and incremental cost-effectiveness.
HIV screening one-time, every five years, and annually increase HIV-infected quality-adjusted life expectancy (mean age 33 years) from 180.6 months (current practice) to 184.9, 187.6 and 197.2 months. The incremental cost-effectiveness of one-time screening is dominated by screening every five years. Screening every five years and annually each have incremental cost-effectiveness ratios of $1,570/quality-adjusted life year (QALY) and $1,720/QALY. Screening annually is very cost-effective even in settings with the lowest incidence/prevalence, with test acceptance and linkage rates both as low as 20%, or when accounting for a stigma impact at least four-fold that of the base case.
In South Africa, annual voluntary HIV screening offers substantial clinical benefit and is very cost-effective, even with highly constrained access to care and treatment.
PMCID: PMC3005842  PMID: 21068674
HIV; screening; cost-effectiveness; South Africa
22.  Expanded HIV Screening in the U.S.: What Will It Cost Government Discretionary and Entitlement Programs? A Budget Impact Analysis 
The US Centers for Disease Control and Prevention (CDC) recently revised their HIV screening guidelines to promote testing and earlier entry to care. Prior analyses have examined the policy’s cost-effectiveness but have not evaluated its impact on government budgets.
We used a simulation model of HIV screening, disease, and treatment to determine the budget impact of expanded HIV screening to US government discretionary, entitlement, and testing programs. We estimated total and incremental testing and treatment costs over a five-year time horizon under current and expanded screening scenarios. We used CDC estimates of HIV prevalence and annual incidence, and considered variations in screening frequency, test return rates, linkage to care, test characteristics, and eligibility for government screening and treatment programs.
Under current practice, 177,000 new HIV cases will be identified over five years. Expanded screening will identify an additional 46,000 cases at an incremental five-year cost of $2.7 billion. The financial burden of expanded HIV screening will fall disproportionately on discretionary programs that fund care for newly identified patients and will not be offset by entitlement program savings. Testing will represent a small proportion (18%) of the total budget increase. Costs are sensitive to the frequency of screening and the proportion linked to care.
The expanded HIV screening program will have a large downstream impact on government programs that fund HIV care. Expanded HIV screening will not meet early treatment goals unless government programs have sufficient budgets to expand testing and provide care for newly-identified cases.
PMCID: PMC2999642  PMID: 20950323
23.  HIV testing rates and outcomes in a South African community, 2001–2006: implications for expanded screening policies 
Revised World Health Organization recommendations seek to increase HIV testing. We assessed the need for expanded testing in South Africa by examining current testing and treatment trends among a high-prevalence population.
We determined the numbers of adults receiving HIV testing and antiretroviral treatment (ART) during 2001–2006 using testing registers linked to patient records from two healthcare facilities believed responsible for virtually all HIV services available to the population. We evaluated annual population testing rates using census population counts; proportions of clients testing seropositive (yield); CD4 counts and WHO stage at diagnosis; and ART initiation rates.
HIV testing rates rose from 4% in 2001 to 20% in 2006 (p<0.001) and were highest among pregnant females receiving provider-initiated testing. Yield for first-time testers decreased from 47% in 2001 to 28% in 2006. Median CD4 counts and WHO stage distributions for newly-diagnosed clients remained stable. HIV-infected clients receiving ART within six months of eligibility increased from 0% in 2001 to 68% in 2006 (p<0.001).
Population testing and ART initiation rates rose dramatically during 2001–2006. Yet, yield remained high and HIV-infected persons continued to receive late diagnoses. These findings highlight the continuing need for expanded testing and linkage to care.
PMCID: PMC3209660  PMID: 19582895
24.  Resource Utilization and Cost-Effectiveness of Counselor- vs. Provider-Based Rapid Point-of-Care HIV Screening in the Emergency Department 
PLoS ONE  2011;6(10):e25575.
Routine HIV screening in emergency department (ED) settings may require dedicated personnel. We evaluated the outcomes, costs and cost-effectiveness of HIV screening when offered by either a member of the ED staff or by an HIV counselor.
We employed a mathematical model to extend data obtained from a randomized clinical trial of provider- vs. counselor-based HIV screening in the ED. We compared the downstream survival, costs, and cost-effectiveness of three HIV screening modalities: 1) no screening program; 2) an ED provider-based program; and 3) an HIV counselor-based program. Trial arm-specific data were used for test offer and acceptance rates (provider offer 36%, acceptance 75%; counselor offer 80%, acceptance 71%). Undiagnosed HIV prevalence (0.4%) and linkage to care rates (80%) were assumed to be equal between the screening modalities. Personnel costs were derived from trial-based resource utilization data. We examined the generalizability of results by conducting sensitivity analyses on offer and acceptance rates, undetected HIV prevalence, and costs.
Estimated HIV screening costs in the provider and counselor arms averaged $8.10 and $31.00 per result received. The Provider strategy (compared to no screening) had an incremental cost-effectiveness ratio of $58,700/quality-adjusted life year (QALY) and the Counselor strategy (compared to the Provider strategy) had an incremental cost-effectiveness ratio of $64,500/QALY. Results were sensitive to the relative offer and acceptance rates by strategy and the capacity of providers to target-screen, but were robust to changes in undiagnosed HIV prevalence and programmatic costs.
The cost-effectiveness of provider-based HIV screening in an emergency department setting compares favorably to other US screening programs. Despite its additional cost, counselor-based screening delivers just as much return on investment as provider based-screening. Investment in dedicated HIV screening personnel is justified in situations where ED staff resources may be insufficient to provide comprehensive, sustainable screening services.
PMCID: PMC3192047  PMID: 22022415
25.  Test and Treat DC: Forecasting the Impact of a Comprehensive HIV Strategy in Washington DC 
US and international agencies have signaled their commitment to containing the HIV epidemic via early case identification and linkage to antiretroviral therapy (ART) immediately upon diagnosis. We forecast outcomes of this approach if implemented in Washington DC.
Using a mathematical model of HIV case detection and treatment, we evaluate combinations of HIV screening and ART initiation strategies. We define current practice as no regular screening program and ART at ≤350/μl, and test and treat as annual screening and ART upon diagnosis. Outcomes include life expectancy of HIV-infected persons and changes in the population time with transmissible HIV RNA. Data, largely from DC, include undiagnosed HIV prevalence 0.6%, annual incidence 0.13%, 31% test offer, 60% acceptance, and 50% linkage to care. Input parameters, including optimized ART efficacy, are varied in sensitivity analyses.
Projected life expectancies, from an initial mean age 41 years, for current practice, test and treat, and test and treat with optimized ART are 23.9, 25.0, and 25.6 years. Compared to current practice, test and treat leads to a 14.7% reduction in time spent with transmissible HIV RNA in the next 5 years; test and treat with optimized ART results in a 27.2% reduction.
An expanded HIV test and treat program in Washington DC will increase life expectancy of HIV-infected patients but will have a modest impact on HIV transmission over the next five years and is unlikely to halt the HIV epidemic.
The CEPAC model shows a test and treat strategy in Washington DC would result in a substantial clinical impact to HIV-infected individuals. Results suggest a need to temper expectations regarding the extent to which test and treat will control the epidemic.
PMCID: PMC2906630  PMID: 20617921
HIV; Test and Treat; Washington DC; HIV screening

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