Publications by authors named "Kenneth A Freedberg"

260 Publications

Evaluating Point-of-Care Nucleic Acid Tests in Adult Human Immunodeficiency Virus Diagnostic Strategies: A Côte d'Ivoire Modeling Analysis.

Open Forum Infect Dis 2021 Jun 13;8(6):ofab225. Epub 2021 May 13.

Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, Massachusetts, USA.

Background: The World Health Organization (WHO) human immunodeficiency virus (HIV) diagnostic strategy requires 6 rapid diagnostic tests (RDTs). Point-of-care nucleic acid tests (POC NATs) are costlier, less sensitive, but more specific than RDTs.

Methods: We simulated a 1-time screening process in Côte d'Ivoire (CI; undiagnosed prevalence: 1.8%), comparing WHO- and CI-recommended RDT-based strategies (RDT-WHO, RDT-CI) and an alternative: POC NAT to resolve RDT discordancy (NAT-Resolve). Costs included assays (RDT: $1.47; POC NAT: $27.92), antiretroviral therapy ($6-$22/month), and HIV care ($27-$38/month). We modeled 2 sensitivity/specificity scenarios: high-performing (RDT: 99.9%/99.1%; POC NAT: 95.0%/100.0%) and low-performing (RDT: 91.1%/82.9%; POC NAT: 93.3%/99.5%). Outcomes included true-positive (TP), false-positive (FP), true-negative (TN), or false-negative (FN) results; life expectancy; costs; and incremental cost-effectiveness ratios (ICERs: $/year of life saved [YLS]; threshold ≤$1720/YLS [per-capita gross domestic product]).

Results: Model-projected impacts of misdiagnoses were 4.4 years lost (FN vs TP; range, 3.0-13.0 years) and a $5800 lifetime cost increase (FP vs TN; range, $590-$14 680). In the high-performing scenario, misdiagnoses/10 000 000 tested were lowest for NAT-Resolve vs RDT-based strategies (FN: 409 vs 413-429; FP: 14 vs 21-28). Strategies had similar life expectancy (228 months) and lifetime costs ($220/person) among all tested; ICERs were $3450/YLS (RDT-CI vs RDT-WHO) and $120 910/YLS (NAT-Resolve vs RDT-CI). In the low-performing scenario, misdiagnoses were higher (FN: 22 845-30 357; FP: 83 724-112 702) and NAT-Resolve was cost-saving.

Conclusions: We projected substantial clinical and economic impacts of misdiagnoses. Using POC NAT to resolve RDT discordancy generated the fewest misdiagnoses and was not cost-effective in high-performing scenarios, but may be an important adjunct to existing RDT-based strategies in low-performing scenarios.
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http://dx.doi.org/10.1093/ofid/ofab225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231387PMC
June 2021

Clinical outcomes and cost-effectiveness of COVID-19 vaccination in South Africa.

medRxiv 2021 May 12. Epub 2021 May 12.

Low- and middle-income countries are implementing COVID-19 vaccination strategies in light of varying and uncertain vaccine efficacies and costs, supply shortages, and resource constraints. We used a microsimulation model to evaluate clinical outcomes and cost-effectiveness of a COVID-19 vaccination program in South Africa. We varied vaccination coverage, pace, acceptance, effectiveness, and cost as well as epidemic dynamics. Providing vaccine to at least 40% of the population and prioritizing accelerated vaccine rollout prevented >9 million infections and >73,000 deaths and reduced costs due to fewer hospitalizations. Further, the vaccination program was cost-saving even at the lowest examined levels of acceptance (50%), effectiveness against infection (20%), effectiveness against symptomatic disease (30%), and effectiveness against severe/critical disease requiring hospitalization (40%), and with vaccination costs of up to USD25/person. In summary, a COVID-19 vaccination program would reduce both deaths and health care costs in South Africa across a wide range of assumptions. Vaccination program implementation factors, including prompt procurement, distribution, and rollout, are likely more influential than characteristics of the vaccine itself in maximizing public health benefits and economic efficiency.
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http://dx.doi.org/10.1101/2021.05.07.21256852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132265PMC
May 2021

Modeling Adherence Interventions Among Youth with HIV in the United States: Clinical and Economic Projections.

AIDS Behav 2021 Feb 6. Epub 2021 Feb 6.

Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

The Adolescent Medicine Trials Network for HIV/AIDS Interventions is evaluating treatment adherence interventions (AI) to improve virologic suppression (VS) among youth with HIV (YWH). Using a microsimulation model, we compared two strategies: standard-of-care (SOC) and a hypothetical 12-month AI that increased cohort-level VS in YWH in care by an absolute ten percentage points and cost $100/month/person. Projected outcomes included primary HIV transmissions, deaths and life-expectancy, lifetime HIV-related costs, and incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year [QALY]). Compared to SOC, AI would reduce HIV transmissions by 15% and deaths by 12% at 12 months. AI would improve discounted life expectancy/person by 8 months at an added lifetime cost/person of $5,300, resulting in an ICER of $7,900/QALY. AI would be cost-effective at $2,000/month/person or with efficacies as low as a 1 percentage point increase in VS. YWH-targeted adherence interventions with even modest efficacy could improve life expectancy, prevent onward HIV transmissions, and be cost-effective.
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http://dx.doi.org/10.1007/s10461-021-03169-0DOI Listing
February 2021

Optimizing infant HIV diagnosis with additional screening at immunization clinics in three sub-Saharan African settings: a cost-effectiveness analysis.

J Int AIDS Soc 2021 01;24(1):e25651

Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA.

Introduction: Uptake of early infant HIV diagnosis (EID) varies widely across sub-Saharan African settings. We evaluated the potential clinical impact and cost-effectiveness of universal maternal HIV screening at infant immunization visits, with referral to EID and maternal antiretroviral therapy (ART) initiation.

Methods: Using the CEPAC-Pediatric model, we compared two strategies for infants born in 2017 in Côte d'Ivoire (CI), South Africa (SA), and Zimbabwe: (1) existing EID programmes offering six-week nucleic acid testing (NAT) for infants with known HIV exposure (EID), and (2) EID plus universal maternal HIV screening at six-week infant immunization visits, leading to referral for infant NAT and maternal ART initiation (screen-and-test). Model inputs included published Ivoirian/South African/Zimbabwean data: maternal HIV prevalence (4.8/30.8/16.1%), current uptake of EID (40/95/65%) and six-week immunization attendance (99/74/94%). Referral rates for infant NAT and maternal ART initiation after screen-and-test were 80%. Costs included NAT ($24/infant), maternal screening ($10/mother-infant pair), ART ($5 to 31/month) and HIV care ($15 to 190/month). Model outcomes included mother-to-child transmission of HIV (MTCT) among HIV-exposed infants, and life expectancy (LE) and mean lifetime per-person costs for children with HIV (CWH) and all children born in 2017. We calculated incremental cost-effectiveness ratios (ICERs) using discounted (3%/year) lifetime costs and LE for all children. We considered two cost-effectiveness thresholds in each country: (1) the per-capita GDP ($1720/6380/2150) per year-of-life saved (YLS), and (2) the CEPAC-generated ICER of offering 2 versus 1 lifetime ART regimens (e.g. offering second-line ART; $520/500/580/YLS).

Results: With EID, projected six-week MTCT was 9.3% (CI), 4.2% (SA) and 5.2% (Zimbabwe). Screen-and-test decreased total MTCT by 0.2% to 0.5%, improved LE by 2.0 to 3.5 years for CWH and 0.03 to 0.07 years for all children, and increased discounted costs by $17 to 22/child (all children). The ICER of screen-and-test compared to EID was $1340/YLS (CI), $650/YLS (SA) and $670/YLS (Zimbabwe), below the per-capita GDP but above the ICER of 2 versus 1 lifetime ART regimens in all countries.

Conclusions: Universal maternal HIV screening at immunization visits with referral to EID and maternal ART initiation may reduce MTCT, improve paediatric LE, and be of comparable value to current HIV-related interventions in high maternal HIV prevalence settings like SA and Zimbabwe.
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http://dx.doi.org/10.1002/jia2.25651DOI Listing
January 2021

Clinical Outcomes, Costs, and Cost-effectiveness of Strategies for Adults Experiencing Sheltered Homelessness During the COVID-19 Pandemic.

JAMA Netw Open 2020 12 1;3(12):e2028195. Epub 2020 Dec 1.

Division of General Internal Medicine, Massachusetts General Hospital, Boston.

Importance: Approximately 356 000 people stay in homeless shelters nightly in the United States. They have high risk of contracting coronavirus disease 2019 (COVID-19).

Objective: To assess the estimated clinical outcomes, costs, and cost-effectiveness associated with strategies for COVID-19 management among adults experiencing sheltered homelessness.

Design, Setting, And Participants: This decision analytic model used a simulated cohort of 2258 adults residing in homeless shelters in Boston, Massachusetts. Cohort characteristics and costs were adapted from Boston Health Care for the Homeless Program. Disease progression, transmission, and outcomes data were taken from published literature and national databases. Surging, growing, and slowing epidemics (effective reproduction numbers [Re], 2.6, 1.3, and 0.9, respectively) were examined. Costs were from a health care sector perspective, and the time horizon was 4 months, from April to August 2020.

Exposures: Daily symptom screening with polymerase chain reaction (PCR) testing of individuals with positive symptom screening results, universal PCR testing every 2 weeks, hospital-based COVID-19 care, alternative care sites (ACSs) for mild or moderate COVID-19, and temporary housing were each compared with no intervention.

Main Outcomes And Measures: Cumulative infections and hospital-days, costs to the health care sector (US dollars), and cost-effectiveness, as incremental cost per case of COVID-19 prevented.

Results: The simulated population of 2258 sheltered homeless adults had a mean (SD) age of 42.6 (9.04) years. Compared with no intervention, daily symptom screening with ACSs for pending tests or confirmed COVID-19 and mild or moderate disease was associated with 37% fewer infections (1954 vs 1239) and 46% lower costs ($6.10 million vs $3.27 million) at an Re of 2.6, 75% fewer infections (538 vs 137) and 72% lower costs ($1.46 million vs $0.41 million) at an Re of 1.3, and 51% fewer infections (174 vs 85) and 51% lower costs ($0.54 million vs $0.26 million) at an Re of 0.9. Adding PCR testing every 2 weeks was associated with a further decrease in infections; incremental cost per case prevented was $1000 at an Re of 2.6, $27 000 at an Re of 1.3, and $71 000 at an Re of 0.9. Temporary housing with PCR every 2 weeks was most effective but substantially more expensive than other options. Compared with no intervention, temporary housing with PCR every 2 weeks was associated with 81% fewer infections (376) and 542% higher costs ($39.12 million) at an Re of 2.6, 82% fewer infections (95) and 2568% higher costs ($38.97 million) at an Re of 1.3, and 59% fewer infections (71) and 7114% higher costs ($38.94 million) at an Re of 0.9. Results were sensitive to cost and sensitivity of PCR and ACS efficacy in preventing transmission.

Conclusions And Relevance: In this modeling study of simulated adults living in homeless shelters, daily symptom screening and ACSs were associated with fewer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and decreased costs compared with no intervention. In a modeled surging epidemic, adding universal PCR testing every 2 weeks was associated with further decrease in SARS-CoV-2 infections at modest incremental cost and should be considered during future surges.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.28195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756240PMC
December 2020

College Campuses and COVID-19 Mitigation: Clinical and Economic Value.

Ann Intern Med 2021 04 21;174(4):472-483. Epub 2020 Dec 21.

Massachusetts General Hospital, Harvard Medical School, and Harvard T.H. Chan School of Public Health, Boston, Massachusetts (K.A.F.).

Background: Colleges in the United States are determining how to operate safely amid the coronavirus disease 2019 (COVID-19) pandemic.

Objective: To examine the clinical outcomes, cost, and cost-effectiveness of COVID-19 mitigation strategies on college campuses.

Design: The Clinical and Economic Analysis of COVID-19 interventions (CEACOV) model, a dynamic microsimulation model, was used to examine alternative mitigation strategies. The CEACOV model tracks infections accrued by students and faculty, accounting for community transmissions.

Data Sources: Data from published literature were used to obtain parameters related to COVID-19 and contact-hours.

Target Population: Undergraduate students and faculty at U.S. colleges.

Time Horizon: One semester (105 days).

Perspective: Modified societal.

Intervention: COVID-19 mitigation strategies, including social distancing, masks, and routine laboratory screening.

Outcome Measures: Infections among students and faculty per 5000 students and per 1000 faculty, isolation days, tests, costs, cost per infection prevented, and cost per quality-adjusted life-year (QALY).

Results Of Base-case Analysis: Among students, mitigation strategies reduced COVID-19 cases from 3746 with no mitigation to 493 with extensive social distancing and masks, and further to 151 when laboratory testing was added among asymptomatic persons every 3 days. Among faculty, these values were 164, 28, and 25 cases, respectively. Costs ranged from about $0.4 million for minimal social distancing to about $0.9 million to $2.1 million for strategies involving laboratory testing ($10 per test), depending on testing frequency. Extensive social distancing with masks cost $170 per infection prevented ($49 200 per QALY) compared with masks alone. Adding routine laboratory testing increased cost per infection prevented to between $2010 and $17 210 (cost per QALY gained, $811 400 to $2 804 600).

Results Of Sensitivity Analysis: Results were most sensitive to test costs.

Limitation: Data are from multiple sources.

Conclusion: Extensive social distancing with a mandatory mask-wearing policy can prevent most COVID-19 cases on college campuses and is very cost-effective. Routine laboratory testing would prevent 96% of infections and require low-cost tests to be economically attractive.

Primary Funding Source: National Institutes of Health.
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http://dx.doi.org/10.7326/M20-6558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755069PMC
April 2021

Cost-effectiveness of a novel lipoarabinomannan test for tuberculosis in patients with HIV.

Clin Infect Dis 2020 Nov 17. Epub 2020 Nov 17.

Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA.

Background: A novel urine lipoarabinomannan assay (FujiLAM) has higher sensitivity and higher cost than the first-generation AlereLAM assay. We evaluated the cost-effectiveness of FujiLAM for tuberculosis testing among hospitalized people with HIV irrespective of symptoms.

Methods: We used a microsimulation model to project clinical and economic outcomes of three testing strategies: 1) sputum Xpert MTB/RIF (Xpert); 2) sputum Xpert plus urine AlereLAM (Xpert+AlereLAM); 3) sputum Xpert plus urine FujiLAM (Xpert+FujiLAM). The modelled cohort matched that of a two-country clinical trial. We applied diagnostic yields from a retrospective study (yields for Xpert/Xpert+AlereLAM/Xpert+FujiLAM among those with CD4<200/µL: 33%/62%/70%; among those with CD4≥200/µL: 33%/35%/47%). Costs of Xpert/AlereLAM/FujiLAM were USD15/3/6 (South Africa) and USD25/3/6 (Malawi). Xpert+FujiLAM was considered cost-effective if its incremental cost-effectiveness ratio (USD/year-of-life saved) was <$940 (South Africa) and <$750 (Malawi). We varied key parameters in sensitivity analysis and performed a budget impact analysis of implementing FujiLAM countrywide.

Results: Compared with Xpert+AlereLAM, Xpert+FujiLAM increased life expectancy by 0.2 years for those tested in South Africa and Malawi. Xpert+FujiLAM was cost-effective in both countries. Xpert+FujiLAM for all patients remained cost-effective compared with sequential testing and CD4-stratified testing strategies. FujiLAM use added 3.5% (South Africa) and 4.7% (Malawi) to five-year healthcare costs of tested patients, primarily reflecting ongoing HIV treatment costs among survivors.

Conclusions: FujiLAM with Xpert for tuberculosis testing in hospitalized people with HIV is likely to increase life expectancy and be cost-effective at the currently anticipated price in South Africa and Malawi. Additional studies should evaluate FujiLAM in clinical practice settings.
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http://dx.doi.org/10.1093/cid/ciaa1698DOI Listing
November 2020

Cost-effectiveness of public health strategies for COVID-19 epidemic control in South Africa: a microsimulation modelling study.

Lancet Glob Health 2021 02 11;9(2):e120-e129. Epub 2020 Nov 11.

Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Africa Health Research Institute, Durban, South Africa.

Background: Health-care resource constraints in low-income and middle-income countries necessitate the identification of cost-effective public health interventions to address COVID-19. We aimed to develop a dynamic COVID-19 microsimulation model to assess clinical and economic outcomes and cost-effectiveness of epidemic control strategies in KwaZulu-Natal province, South Africa.

Methods: We compared different combinations of five public health interventions: health-care testing alone, where diagnostic testing is done only for individuals presenting to health-care centres; contact tracing in households of cases; isolation centres, for cases not requiring hospital admission; mass symptom screening and molecular testing for symptomatic individuals by community health-care workers; and quarantine centres, for household contacts who test negative. We calibrated infection transmission rates to match effective reproduction number (R) estimates reported in South Africa. We assessed two main epidemic scenarios for a period of 360 days, with an R of 1·5 and 1·2. Strategies with incremental cost-effectiveness ratio (ICER) of less than US$3250 per year of life saved were considered cost-effective. We also did sensitivity analyses by varying key parameters (R values, molecular testing sensitivity, and efficacies and costs of interventions) to determine the effect on clinical and cost projections.

Findings: When R was 1·5, health-care testing alone resulted in the highest number of COVID-19 deaths during the 360-day period. Compared with health-care testing alone, a combination of health-care testing, contact tracing, use of isolation centres, mass symptom screening, and use of quarantine centres reduced mortality by 94%, increased health-care costs by 33%, and was cost-effective (ICER $340 per year of life saved). In settings where quarantine centres were not feasible, a combination of health-care testing, contact tracing, use of isolation centres, and mass symptom screening was cost-effective compared with health-care testing alone (ICER $590 per year of life saved). When R was 1·2, health-care testing, contact tracing, use of isolation centres, and use of quarantine centres was the least costly strategy, and no other strategies were cost-effective. In sensitivity analyses, a combination of health-care testing, contact tracing, use of isolation centres, mass symptom screening, and use of quarantine centres was generally cost-effective, with the exception of scenarios in which R was 2·6 and when efficacies of isolation centres and quarantine centres for transmission reduction were reduced.

Interpretation: In South Africa, strategies involving household contact tracing, isolation, mass symptom screening, and quarantining household contacts who test negative would substantially reduce COVID-19 mortality and would be cost-effective. The optimal combination of interventions depends on epidemic growth characteristics and practical implementation considerations.

Funding: US National Institutes of Health, Royal Society, Wellcome Trust.
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http://dx.doi.org/10.1016/S2214-109X(20)30452-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834260PMC
February 2021

Comparative effectiveness of interventions to improve the HIV continuum of care and HIV Pre-Exposure Prophylaxis in Kenya: a model-based analysis.

J Infect Dis 2020 Oct 27. Epub 2020 Oct 27.

From Université de Paris, IAME, INSERM, Paris, France.

Background: In Western Kenya up to one quarter of the adult population was HIV-infected in 2012. The Ministry of Health, Médecins Sans Frontières (MSF) and partners implemented an HIV program that surpassed the 90-90-90 UNAIDS targets. In this generalized epidemic, we compared the effectiveness of Pre-exposure Prophylaxis (PrEP) with improving the continuum of care.

Methods: We developed a dynamic microsimulation model to project HIV incidence and infections averted to 2030. We modeled 3 strategies compared to a "90-90-90" continuum of care base case: 1) Scaling up the continuum of care to 95-95-95, 2) PrEP targeting young adults, with 10% coverage, and 3) Scaling up to 95-95-95 and PrEP combined.

Results: In the base case, by 2030 HIV incidence was 0.37/100 PY. Improving continuum levels to 95-95-95 averted 21.5% of infections, PrEP 8.0%, and combining 95-95-95 and PrEP 31.8%. Sensitivity analysis showed that PrEP coverage had to exceed 20% to avert as many infections as reaching 95-95-95.

Conclusions: In a generalized HIV epidemic with continuum of care levels at 90-90-90, improving the continuum to 95-95-95 is more effective than providing PrEP. Continued improvement in the continuum of care will have the greatest impact on decreasing new HIV infections.
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http://dx.doi.org/10.1093/infdis/jiaa633DOI Listing
October 2020

The impact of user fees on uptake of HIV services and adherence to HIV treatment: Findings from a large HIV program in Nigeria.

PLoS One 2020 8;15(10):e0238720. Epub 2020 Oct 8.

Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, Massachusetts, United States of America.

Background: Global HIV funding cutbacks have been accompanied by the adoption of user fees to address funding gaps in treatment programs. Our objective was to assess the impact of user fees on HIV care utilization and medication adherence in Nigeria.

Methods: We conducted a retrospective analysis of patients enrolled in care before (October 2012-September 2013) and after (October 2014-September 2015) the introduction of user fees in a Nigerian clinic. We assessed pre- vs. post-user fee patient characteristics and enrollment trends, and determined risk of care interruption, loss to follow-up, and optimal medication adherence.

Results: After fees were instituted, there was a 66% decline in patient enrollment and 75% decline in number of ART doses dispensed. There was no difference in the proportion of female clients (64% vs 63%, p = 0.46), average age (36 vs. 37 years, p = 0.15), or median baseline CD4 (220/ul vs. 222/uL, p = 0.24) in pre- and post-fee cohorts. There was an increase in clients employed and/or had tertiary education (24% vs. 32%, p<0.001). Compared to pre-fee patients, the post-fee period had a 48% decreased risk of care interruption (aRR = 0.52, 95%CI:0.39-0.69), 22% decreased LTFU risk (aRR = 0.64, 95%CI:0.96), and 27% decreased odds of optimal medication adherence (aOR = 0.7, 3 95%CI 0.59-0.89).

Conclusions: Patients enrolled in care after introduction of user fees in Nigeria were more likely to be educated or employed, and effectively retained in care after starting ART. However, fees were accompanied by a drastic reduction in new patient enrollment, suggesting that many patients may have been marginalized from HIV care.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238720PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544141PMC
November 2020

Clinical Impact, Costs, and Cost-Effectiveness of Expanded SARS-CoV-2 Testing in Massachusetts.

Clin Infect Dis 2020 Sep 18. Epub 2020 Sep 18.

Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA.

Background: We projected the clinical and economic impact of alternative testing strategies on COVID-19 incidence and mortality in Massachusetts using a microsimulation model.

Methods: We compared four testing strategies: 1) Hospitalized: PCR testing only patients with severe/critical symptoms warranting hospitalization; 2) Symptomatic: PCR for any COVID-19-consistent symptoms, with self-isolation if positive; 3) Symptomatic+asymptomatic-once: Symptomatic and one-time PCR for the entire population; and, 4) Symptomatic+asymptomatic-monthly: Symptomatic with monthly re-testing for the entire population. We examined effective reproduction numbers (Re, 0.9-2.0) at which policy conclusions would change. We assumed homogeneous mixing among the Massachusetts population (excluding those residing in long-term care facilities). We used published data on disease progression and mortality, transmission, PCR sensitivity/specificity (70/100%) and costs. Model-projected outcomes included infections, deaths, tests performed, hospital-days, and costs over 180-days, as well as incremental cost-effectiveness ratios (ICER, $/quality-adjusted life-year [QALY]).

Results: At Re 0.9, Symptomatic+asymptomatic-monthly vs. Hospitalized resulted in a 64% reduction in infections and a 46% reduction in deaths, but required >66-fold more tests/day with 5-fold higher costs. Symptomatic+asymptomatic-monthly had an ICER <$100,000/QALY only when Re ≥1.6; when test cost was ≤$3, every 14-day testing was cost-effective at all Re examined.

Conclusions: Testing people with any COVID-19-consistent symptoms would be cost-saving compared to testing only those whose symptoms warrant hospital care. Expanding PCR testing to asymptomatic people would decrease infections, deaths, and hospitalizations. Despite modest sensitivity, low-cost, repeat screening of the entire population could be cost-effective in all epidemic settings.
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http://dx.doi.org/10.1093/cid/ciaa1418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543346PMC
September 2020

College campuses and COVID-19 mitigation: clinical and economic value.

medRxiv 2020 Sep 5. Epub 2020 Sep 5.

Background: Decisions around US college and university operations will affect millions of students and faculty amidst the COVID-19 pandemic. We examined the clinical and economic value of different COVID-19 mitigation strategies on college campuses.

Methods: We used the Clinical and Economic Analysis of COVID-19 interventions (CEACOV) model, a dynamic microsimulation that tracks infections accrued by students and faculty, accounting for community transmissions. Outcomes include infections, $/infection-prevented, and $/quality-adjusted-life-year ($/QALY). Strategies included extensive social distancing (ESD), masks, and routine laboratory tests (RLT). We report results per 5,000 students (1,000 faculty) over one semester (105 days).

Results: Mitigation strategies reduced COVID-19 cases among students (faculty) from 3,746 (164) with no mitigation to 493 (28) with ESD and masks, and further to 151 (25) adding RLTq3 among asymptomatic students and faculty. ESD with masks cost $168/infection-prevented ($49,200/QALY) compared to masks alone. Adding RLTq3 ($10/test) cost $8,300/infection-prevented ($2,804,600/QALY). If tests cost $1, RLTq3 led to a favorable cost of $275/infection-prevented ($52,200/QALY). No strategies without masks were cost-effective.

Conclusion: Extensive social distancing with mandatory mask-wearing could prevent 87% of COVID-19 cases on college campuses and be very cost-effective. Routine laboratory testing would prevent 96% of infections and require low cost tests to be economically attractive.
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http://dx.doi.org/10.1101/2020.09.03.20187062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480037PMC
September 2020

Management Strategies for People Experiencing Sheltered Homelessness during the COVID-19 Pandemic: Clinical Outcomes and Costs.

medRxiv 2020 Aug 11. Epub 2020 Aug 11.

Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA.

Importance: Approximately 356,000 people stay in homeless shelters nightly in the US. These individuals are at high risk for COVID-19.

Objective: To assess clinical outcomes, costs, and cost-effectiveness of strategies for COVID-19 prevention and management among sheltered homeless adults.

Design: We developed a dynamic microsimulation model of COVID-19. We modeled sheltered homeless adults in Boston, Massachusetts, using cohort characteristics and costs from Boston Health Care for the Homeless Program. Disease progression, transmission, and clinical outcomes data were from published literature and national databases. We examined surging, growing, and slowing epidemics (effective reproduction numbers [Re] 2.6, 1.3, and 0.9). Costs were from a health care sector perspective; time horizon was 4 months.

Setting & Participants: Simulated cohort of 2,258 adults residing in homeless shelters in Boston.

Interventions: We assessed combinations of daily symptom screening with same-day polymerase chain reaction (PCR) testing of screen-positive individuals, universal PCR testing every 2 weeks, hospital-based COVID-19 care, alternate care sites [ACSs] for mild/moderate COVID-19 management, and moving people from shelters to temporary housing, compared to no intervention.

Main Outcomes: Infections, hospital-days, costs, and cost-effectiveness.

Results: Compared to no intervention, daily symptom screening with ACSs for those with pending tests or confirmed COVID-19 and mild/moderate disease leads to 37% fewer infections and 46% lower costs when Re=2.6, 75% fewer infections and 72% lower costs when Re=1.3, and 51% fewer infections and 51% lower costs when Re=0.9. Adding universal PCR testing every 2 weeks further decreases infections in all epidemic scenarios, with incremental cost per case prevented of $1,000 (Re=2.6), $27,000 (Re=1.3), and $71,000 (Re=0.9). In all scenarios, moving shelter residents to temporary housing with universal PCR testing every 2 weeks is most effective but substantially more costly than other options. Results are most sensitive to the cost and sensitivity of PCR testing and the efficacy of ACSs in preventing transmission. Conclusions & Relevance: Daily symptom screening and ACSs for sheltered homeless adults will substantially decrease COVID-19 cases and reduce costs compared to no intervention. In a surging epidemic, adding universal PCR testing every 2 weeks further decreases cases at modest incremental cost and should be considered.
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http://dx.doi.org/10.1101/2020.08.07.20170498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430611PMC
August 2020

Clinical Impact, Costs, and Cost-Effectiveness of Expanded SARS-CoV-2 Testing in Massachusetts.

medRxiv 2020 Jul 24. Epub 2020 Jul 24.

Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA.

Background We projected the clinical and economic impact of alternative testing strategies on COVID-19 incidence and mortality in Massachusetts using a microsimulation model. Methods We compared five testing strategies: 1) PCR-severe-only: PCR testing only patients with severe/critical symptoms; 2) Self-screen: PCR-severe-only plus self-assessment of COVID-19-consistent symptoms with self-isolation if positive; 3) PCR-any-symptom: PCR for any COVID-19-consistent symptoms with self-isolation if positive; 4) PCR-all: PCR-any-symptom and one-time PCR for the entire population; and, 5) PCR-all-repeat: PCR-all with monthly re-testing. We examined effective reproduction numbers (R , 0.9-2.0) at which policy conclusions would change. We used published data on disease progression and mortality, transmission, PCR sensitivity/specificity (70/100%) and costs. Model-projected outcomes included infections, deaths, tests performed, hospital-days, and costs over 180-days, as well as incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year [QALY]). Results In all scenarios, PCR-all-repeat would lead to the best clinical outcomes and PCR-severe-only would lead to the worst; at R 0.9, PCR-all-repeat vs. PCR-severe-only resulted in a 63% reduction in infections and a 44% reduction in deaths, but required >65-fold more tests/day with 4-fold higher costs. PCR-all-repeat had an ICER <$100,000/QALY only when R ≥1.8. At all R values, PCR-any-symptom was cost-saving compared to other strategies. Conclusions Testing people with any COVID-19-consistent symptoms would be cost-saving compared to restricting testing to only those with symptoms severe enough to warrant hospital care. Expanding PCR testing to asymptomatic people would decrease infections, deaths, and hospitalizations. Universal screening would be cost-effective when paired with monthly retesting in settings where the COVID-19 pandemic is surging.
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http://dx.doi.org/10.1101/2020.07.23.20160820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386528PMC
July 2020

Cost-effectiveness of frequent HIV screening among high-risk young men who have sex with men in the United States.

Clin Infect Dis 2020 Jul 30. Epub 2020 Jul 30.

Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA.

Background: Of new HIV infections in the US, 20% occur among young men who have sex with men (YMSM, ages 13-24), but >50% of YMSM with HIV are unaware of their status. Using Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) data, we projected the clinical benefit and cost-effectiveness of frequent HIV screening among high-risk YMSM from age 15.

Methods: Using a mathematical simulation, we examined 3 screening strategies: Yearly, 6-monthly, and 3-monthly, each in addition to the Status quo (SQ, 0.7-10.3% screened/year, stratified by age). We used published data (YMSM-specific when available) including: HIV incidences (0.91-6.41/100PY); screen acceptance (80%), linkage-to-care/antiretroviral therapy (ART) initiation (76%), HIV transmission (0.3-86.1/100PY, by HIV RNA), monthly ART costs ($2,290-$3,780), and HIV per-screen costs ($38). Projected outcomes included CD4 count at diagnosis, primary HIV transmissions from ages 15-30, quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year saved [QALY]; threshold ≤$100,000/QALY).

Results: Compared to SQ, all strategies increased projected CD4 at diagnosis (296 to 477-515 cells/µL) and quality-adjusted life expectancy from age 15 (44.4 to 48.3-48.7 years) among YMSM acquiring HIV. Compared to SQ, all strategies increased discounted lifetime cost for the entire population ($170,800 to $178,100-$185,000/person). Screening 3-monthly was cost-effective (ICER: $4,500/QALY) compared to SQ and reduced primary transmissions through age 30 by 40%. Results were most sensitive to transmission rates; excluding the impact of transmissions, screening Yearly was ≤$100,000/QALY (ICER: $70,900/QALY).

Conclusions: For high-risk YMSM in the US, HIV screening 3-monthly compared to less frequent screening will improve clinical outcomes and be cost-effective.
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http://dx.doi.org/10.1093/cid/ciaa1061DOI Listing
July 2020

Cost-effectiveness of public health strategies for COVID-19 epidemic control in South Africa.

medRxiv 2020 Jul 1. Epub 2020 Jul 1.

Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA.

Background Healthcare resource constraints in low and middle-income countries necessitate selection of cost-effective public health interventions to address COVID-19. Methods We developed a dynamic COVID-19 microsimulation model to evaluate clinical and economic outcomes and cost-effectiveness of epidemic control strategies in KwaZulu-Natal, South Africa. Interventions assessed were Healthcare Testing (HT), where diagnostic testing is performed only for those presenting to healthcare centres; Contact Tracing (CT) in households of cases; Isolation Centres (IC), for cases not requiring hospitalisation; community health worker-led Mass Symptom Screening and diagnostic testing for symptomatic individuals (MS); and Quarantine Centres (QC), for contacts who test negative. Given uncertainties about epidemic dynamics in South Africa, we evaluated two main epidemic scenarios over 360 days, with effective reproduction numbers (R ) of 1.5 and 1.2. We compared HT, HT+CT, HT+CT+IC, HT+CT+IC+MS, HT+CT+IC+QC, and HT+CT+IC+MS+QC, considering strategies with incremental cost-effectiveness ratio (ICER)
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http://dx.doi.org/10.1101/2020.06.29.20140111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340205PMC
July 2020

Developing and Validating Metamodels of a Microsimulation Model of Infant HIV Testing and Screening Strategies Used in a Decision Support Tool for Health Policy Makers.

MDM Policy Pract 2020 Jan-Jun;5(1):2381468320932894. Epub 2020 Jun 12.

Medical Practice Evaluation Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.

Metamodels can simplify complex health policy models and yield instantaneous results to inform policy decisions. We investigated the predictive validity of linear regression metamodels used to support a real-time decision-making tool that compares infant HIV testing/screening strategies. We developed linear regression metamodels of the Cost-Effectiveness of Preventing AIDS Complications Pediatric (CEPAC-P) microsimulation model used to predict life expectancy and lifetime HIV-related costs/person of two infant HIV testing/screening programs in South Africa. Metamodel performance was assessed with cross-validation and Bland-Altman plots, showing between-method differences in predicted outcomes against their means. Predictive validity was determined by the percentage of simulations in which the metamodels accurately predicted the strategy with the greatest net health benefit (NHB) as projected by the CEPAC-P model. We introduced a zone of indifference and investigated the width needed to produce between-method agreement in 95% of the simulations. We also calculated NHB losses from "wrong" decisions by the metamodel. In cross-validation, linear regression metamodels accurately approximated CEPAC-P-projected outcomes. For life expectancy, Bland-Altman plots showed good agreement between CEPAC-P and the metamodel (within 1.1 life-months difference). For costs, 95% of between-method differences were within $65/person. The metamodels predicted the same optimal strategy as the CEPAC-P model in 87.7% of simulations, increasing to 95% with a zone of indifference of 0.24 life-months ( ∼ 7 days). The losses in health benefits due to "wrong" choices by the metamodel were modest (range: 0.0002-1.1 life-months). For this policy question, linear regression metamodels offered sufficient predictive validity for the optimal testing strategy as compared with the CEPAC-P model. Metamodels can simulate different scenarios in real time, based on sets of input parameters that can be depicted in a widely accessible decision-support tool.
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http://dx.doi.org/10.1177/2381468320932894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294506PMC
June 2020

A novel method to estimate the indirect community benefit of HIV interventions using a microsimulation model of HIV disease.

J Biomed Inform 2020 07 8;107:103475. Epub 2020 Jun 8.

Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA; Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.

Background: Microsimulation models of human immunodeficiency virus (HIV) disease that simulate individual patients one at a time and assess clinical and economic outcomes of HIV interventions often provide key details regarding direct individual clinical benefits ("individual benefit"), but they may lack detail on transmissions, and thus may underestimate an intervention's indirect benefits ("community benefit"). Dynamic transmission models can be used to simulate HIV transmissions, but they may do so at the expense of the clinical detail of microsimulations. We sought to develop, validate, and demonstrate a practical, novel method that can be integrated into existing HIV microsimulation models to capture this community benefit, integrating the effects of reduced transmission while keeping the clinical detail of microsimulations.

Methods: We developed a new method to capture the community benefit of HIV interventions by estimating HIV transmissions from the primary cohort of interest. The method captures the benefit of averting infections within the cohort of interest by estimating a corresponding gradual decline in incidence within the cohort. For infections averted outside the cohort of interest, our method estimates transmissions averted based on reductions in HIV viral load within the cohort, and the benefit (life-years gained and cost savings) of averting those infections based on the time they were averted. To assess the validity of our method, we paired it with the Cost-effectiveness of Preventing AIDS Complications (CEPAC) Model - a validated and widely-published microsimulation model of HIV disease. We then compared the consistency of model-estimated outcomes against outcomes of a widely-validated dynamic compartmental transmission model of HIV disease, the HIV Optimization and Prevention Economics (HOPE) model, using the intraclass correlation coefficient (ICC) with a two-way mixed effects model. Replicating an analysis done with HOPE, validation endpoints were number of HIV transmissions averted by offering pre-exposure prophylaxis (PrEP) to men who have sex with men (MSM) and people who inject drugs (PWID) in the US at various uptake and efficacy levels. Finally, we demonstrated an application of our method in a different setting by evaluating the clinical and economic outcomes of a PrEP program for MSM in India, a country currently considering PrEP rollout for this high-risk group.

Results: The new method paired with CEPAC demonstrated excellent consistency with the HOPE model (ICC = 0.98 for MSM and 0.99 for PWID). With only the individual benefit of the intervention incorporated, a PrEP program for MSM in India averted 43,000 transmissions over a 5-year period and resulted in a lifetime incremental cost-effectiveness ratio (ICER) of US$2,300/year-of-life saved (YLS) compared to the status quo. After applying both the direct (individual) and indirect (community) benefits, PrEP averted 86,000 transmissions over the same period and resulted in an ICER of US$600/YLS.

Conclusions: Our method enables HIV microsimulation models that evaluate clinical and economic outcomes of HIV interventions to estimate the community benefit of these interventions (in terms of survival gains and cost savings) efficiently and without sacrificing clinical detail. This method addresses an important methodological gap in health economics microsimulation modeling and allows decision scientists to make more accurate policy recommendations.
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http://dx.doi.org/10.1016/j.jbi.2020.103475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374016PMC
July 2020

Strengthening Existing Laboratory-Based Systems vs. Investing in Point-of-Care Assays for Early Infant Diagnosis of HIV: A Model-Based Cost-Effectiveness Analysis.

J Acquir Immune Defic Syndr 2020 07;84 Suppl 1:S12-S21

Department of Medicine, Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA.

Background: To improve early infant HIV diagnosis (EID) programs, options include replacing laboratory-based tests with point-of-care (POC) assays or investing in strengthened systems for sample transport and result return.

Setting: We used the CEPAC-Pediatric model to examine clinical benefits and costs of 3 EID strategies in Zimbabwe for infants 6 weeks of age.

Methods: We examined (1) laboratory-based EID (LAB), (2) strengthened laboratory-based EID (S-LAB), and (3) POC EID (POC). LAB/S-LAB and POC assays differed in sensitivity (LAB/S-LAB 100%, POC 96.9%) and specificity (LAB/S-LAB 99.6%, POC 99.9%). LAB/S-LAB/POC algorithms also differed in: probability of result return (79%/91%/98%), time until result return (61/53/1 days), probability of initiating antiretroviral therapy (ART) after positive result (52%/71%/86%), and total cost/test ($18.10/$30.47/$30.71). We projected life expectancy (LE) and average lifetime per-person cost for all HIV-exposed infants. We calculated incremental cost-effectiveness ratios (ICERs) from discounted (3%/year) LE and costs in $/year-of-life saved (YLS), defining cost effective as an ICER <$580/YLS (reflecting programs providing 2 vs. 1 ART regimens). In sensitivity analyses, we varied differences between S-LAB and POC in result return probability, result return time, ART initiation probability, and cost.

Results: For infants who acquired HIV, LAB/S-LAB/POC led to projected one-year survival of 67.3%/69.9%/75.6% and undiscounted LE of 21.74/22.71/24.49 years. For all HIV-exposed infants, undiscounted LE was 63.35/63.38/63.43 years, at discounted lifetime costs of $200/220/240 per infant. In cost-effectiveness analysis, S-LAB was an inefficient use of resources; the ICER of POC vs. LAB was $830/YLS.

Conclusions: Current EID programs will attain greater benefit from investing in POC EID rather than strengthening laboratory-based systems.
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http://dx.doi.org/10.1097/QAI.0000000000002384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302325PMC
July 2020

Waiting for Certainty on Covid-19 Antibody Tests - At What Cost?

N Engl J Med 2020 Aug 5;383(6):e37. Epub 2020 Jun 5.

From the Department of Health Policy and Management, Harvard T.H. Chan School of Public Health (M.C.W.), and the Medical Practice Evaluation Center, Massachusetts General Hospital and Harvard Medical School (K.A.F., E.P.H.) - all in Boston; and the Public Health Modeling Unit, Yale School of Public Health, New Haven, CT (A.D.P.).

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http://dx.doi.org/10.1056/NEJMp2017739DOI Listing
August 2020

Novel microsimulation model of tobacco use behaviours and outcomes: calibration and validation in a US population.

BMJ Open 2020 05 12;10(5):e032579. Epub 2020 May 12.

Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, Massachusetts, USA.

Background And Objective: Simulation models can project effects of tobacco use and cessation and inform tobacco control policies. Most existing tobacco models do not explicitly include relapse, a key component of the natural history of tobacco use. Our objective was to develop, calibrate and validate a novel individual-level microsimulation model that would explicitly include smoking relapse and project cigarette smoking behaviours and associated mortality risks.

Methods: We developed the Simulation of Tobacco and Nicotine Outcomes and Policy (STOP) model, in which individuals transition monthly between tobacco use states (current/former/never) depending on rates of initiation, cessation and relapse. Simulated individuals face tobacco use-stratified mortality risks. For US women and men, we conducted cross-validation with a Cancer Intervention and Surveillance Modeling Network (CISNET) model. We then incorporated smoking relapse and calibrated cessation rates to reflect the difference between a transient quit attempt and sustained abstinence. We performed external validation with the National Health Interview Survey (NHIS) and the linked National Death Index. Comparisons were based on root-mean-square error (RMSE).

Results: In cross-validation, STOP-generated projections of current/former/never smoking prevalence fit CISNET-projected data well (coefficient of variation (CV)-RMSE≤15%). After incorporating smoking relapse, multiplying the CISNET-reported cessation rates for women/men by 7.75/7.25, to reflect the ratio of quit attempts to sustained abstinence, resulted in the best approximation to CISNET-reported smoking prevalence (CV-RMSE 2%/3%). In external validation using these new multipliers, STOP-generated cumulative mortality curves for 20-year-old current smokers and never smokers each had CV-RMSE ≤1% compared with NHIS. In simulating those surveyed by NHIS in 1997, the STOP-projected prevalence of current/former/never smokers annually (1998-2009) was similar to that reported by NHIS (CV-RMSE 12%).

Conclusions: The STOP model, with relapse included, performed well when validated to US smoking prevalence and mortality. STOP provides a flexible framework for policy-relevant analysis of tobacco and nicotine product use.
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http://dx.doi.org/10.1136/bmjopen-2019-032579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228509PMC
May 2020

Comparative Pricing of Branded Tenofovir Alafenamide-Emtricitabine Relative to Generic Tenofovir Disoproxil Fumarate-Emtricitabine for HIV Preexposure Prophylaxis: A Cost-Effectiveness Analysis.

Ann Intern Med 2020 05 10;172(9):583-590. Epub 2020 Mar 10.

Yale School of Public Health, New Haven, Connecticut (A.D.P.).

Background: Tenofovir alafenamide-emtricitabine (F/TAF) was recently approved as a noninferior and potentially safer option than tenofovir disoproxil fumarate-emtricitabine (F/TDF) for HIV preexposure prophylaxis (PrEP) in the United States.

Objective: To estimate the greatest possible clinical benefits and economic savings attributable to the improved safety profile of F/TAF and the maximum price payers should be willing to pay for F/TAF over generic F/TDF.

Design: Cost-effectiveness analysis.

Data Sources: Published literature on F/TDF safety (in persons with and those without HIV) and the cost and quality-of-life effects of fractures and end-stage renal disease (ESRD).

Target Population: Age-stratified U.S. men who have sex with men (MSM) using PrEP.

Time Horizon: Five years.

Perspective: Health care sector.

Intervention: Preexposure prophylaxis with F/TAF versus F/TDF.

Outcome Measures: Fractures averted, cases of ESRD averted, quality-adjusted life-years (QALYs) saved, costs, incremental cost-effectiveness ratios (ICERs), and maximum justifiable price for F/TAF compared with generic F/TDF.

Results Of Base-case Analysis: Over a 5-year horizon, compared with F/TDF, F/TAF averted 2101 fractures and 25 cases of ESRD for the 123 610 MSM receiving PrEP, with an ICER of more than $7 million per QALY. At a 50% discount for generic F/TDF ($8300 per year) and a societal willingness to pay up to $100 000 per QALY, the maximum fair price for F/TAF was $8670 per year.

Results Of Sensitivity Analysis: Among persons older than 55 years, the ICER for F/TAF remained more than $3 million per QALY and the maximum permissible fair price for F/TAF was $8970 per year. Results were robust to alternative time horizons and PrEP-using population sizes.

Limitation: Intermittent use and on-demand PrEP were not considered.

Conclusion: In the presence of a generic F/TDF alternative, the improved safety of F/TAF is worth no more than an additional $370 per person per year.

Primary Funding Source: National Institute of Allergy and Infectious Diseases, National Institute on Drug Abuse, National Institute of Mental Health, and Massachusetts General Hospital Executive Committee on Research.
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http://dx.doi.org/10.7326/M19-3478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217721PMC
May 2020

The Challenges of Parameterizing Direct Effects in Individual-Level Simulation Models.

Med Decis Making 2020 01;40(1):106-111

Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.

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http://dx.doi.org/10.1177/0272989X19894940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989037PMC
January 2020

Clinical and Economic Impact of Ibalizumab for People With Multidrug-Resistant HIV in the United States.

J Acquir Immune Defic Syndr 2020 02;83(2):148-156

Department of Medicine, Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA.

Background: We projected the clinical outcomes, cost-effectiveness, and budget impact of ibalizumab plus an optimized background regimen (OBR) for people with multidrug-resistant (MDR) HIV in the United States.

Methods: Using the Cost-Effectiveness of Preventing AIDS Complications microsimulation model and a health care sector perspective, we compared 2 treatment strategies for MDR HIV: (1) IBA + OBR-ibalizumab plus OBR and (2) OBR-OBR alone. Ibalizumab efficacy and cohort characteristics were from trial data: mean age 49 years, 85% male, and mean CD4 150/µL. Six-month viral suppression was 50% with IBA + OBR and 0% with OBR. The ibalizumab loading dose cost $10,500, and subsequent ibalizumab injections cost $8400/month; OBR cost $4500/month. Incremental cost-effectiveness ratios (ICERs) were calculated using discounted (3%/year) quality-adjusted life years (QALYs) and costs. ICERs ≤$100,000/QALY were considered cost-effective. We performed sensitivity analysis on key parameters and examined budget impact.

Results: In the base case, 5-year survival increased from 38% with OBR to 47% with IBA + OBR. Lifetime costs were $301,700/person with OBR and $661,800/person with IBA + OBR; the ICER for IBA + OBR compared with OBR was $260,900/QALY. IBA + OBR was not cost-effective even with 100% efficacy. IBA + OBR became cost-effective at base case efficacy if ibalizumab cost was reduced by ≥88%. For an estimated 12,000 people with MDR HIV in the United States, IBA + OBR increased care costs by $1.8 billion (1.5% of total treatment budget) over 5 years.

Conclusions: For people with MDR HIV lacking other treatment options, ibalizumab will substantially increase survival when effective. Although adding ibalizumab to OBR is not cost-effective, the low number of eligible patients in the United States makes the budget impact relatively small.
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http://dx.doi.org/10.1097/QAI.0000000000002241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066538PMC
February 2020

Cost-effectiveness of a Medical Care Coordination Program for People With HIV in Los Angeles County.

Open Forum Infect Dis 2019 Dec 16;6(12):ofz537. Epub 2019 Dec 16.

Divisions of General Internal Medicine and Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Background: The Los Angeles County (LAC) Division of HIV and STD Programs implemented a medical care coordination (MCC) program to address the medical and psychosocial service needs of people with HIV (PWH) at risk for poor health outcomes.

Methods: Our objective was to evaluate the impact and cost-effectiveness of the MCC program. Using the CEPAC-US model populated with clinical characteristics and costs observed from the MCC program, we projected lifetime clinical and economic outcomes for a cohort of high-risk PWH under 2 strategies: (1) No MCC and (2) a 2-year MCC program. The cohort was stratified by acuity using social and clinical characteristics. Baseline viral suppression was 33% in both strategies; 2-year suppression was 33% with No MCC and 57% with MCC. The program cost $2700/person/year. Model outcomes included quality-adjusted life expectancy, lifetime medical costs, and cost-effectiveness. The cost-effectiveness threshold for the incremental cost-effectiveness ratio (ICER) was $100 000/quality-adjusted life-year (QALY).

Results: With MCC, life expectancy increased from 10.07 to 10.94 QALYs, and costs increased from $311 300 to $335 100 compared with No MCC (ICER, $27 400/QALY). ICERs for high/severe, moderate, and low acuity were $30 500/QALY, $25 200/QALY, and $77 400/QALY. In sensitivity analysis, MCC remained cost-effective if 2-year viral suppression was ≥39% even if MCC costs increased 3-fold.

Conclusions: The LAC MCC program improved survival and was cost-effective. Similar programs should be considered in other settings to improve outcomes for high-risk PWH.
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http://dx.doi.org/10.1093/ofid/ofz537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935680PMC
December 2019

"Cure" Versus "Clinical Remission": The Impact of a Medication Description on the Willingness of People Living with HIV to Take a Medication.

AIDS Behav 2020 Jul;24(7):2054-2061

School of Medicine, Duke University, 2301 Erwin Rd, Durham, North Carolina, 27710, USA.

Many people living with HIV (PLWHIV) state that they would be willing to take significant risks to be "cured" of the virus. However, how they interpret the word "cure" in this context is not clear. We used a randomized survey to examine whether PLWHIV had a different willingness to take a hypothetical HIV medication if it causes flu-like symptoms, but provides: (a) cure, (b) remission that was labeled "cure", or (c) remission. PLWHIV (n = 454) were more willing to take a medication that provided a "cure" versus a "remission" if the side effects lasted less than 1 year. PLWHIV were more willing to take a medication that provided a remission that was labeled "cure" versus a "remission" (p = 0.01) if the side effects lasted 2 weeks. Clinicians and researchers should be aware of the impact of the word "cure" and ensure that PLWHIV fully understand the possible outcomes of their treatment options.
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http://dx.doi.org/10.1007/s10461-019-02769-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319892PMC
July 2020

Cost-effectiveness of integrating postpartum antiretroviral therapy and infant care into maternal & child health services in South Africa.

PLoS One 2019 15;14(11):e0225104. Epub 2019 Nov 15.

Medical Practice Evaluation Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, United States of America.

Background: Poor engagement in postpartum maternal HIV care is a challenge worldwide and contributes to adverse maternal outcomes and vertical transmission. Our objective was to project the clinical and economic impact of integrated postpartum maternal antiretroviral therapy (ART) and pediatric care in South Africa.

Methods: Using the CEPAC computer simulation models, parameterized with data from the Maternal and Child Health-Antiretroviral Therapy (MCH-ART) randomized controlled trial, we evaluated the cost-effectiveness of integrated postpartum care for women initiating ART in pregnancy and their children. We compared two strategies: 1) standard of care (SOC) referral to local clinics after delivery for separate standard ART services for women and pediatric care for infants, and 2) the MCH-ART intervention (MCH-ART) of co-located maternal/pediatric care integrated in Maternal and Child Health (MCH) services throughout breastfeeding. Trial-derived inputs included: 12-month maternal retention in care and virologic suppression (SOC: 49%, MCH-ART: 67%), breastfeeding duration (SOC: 6 months, MCH-ART: 8 months), and postpartum healthcare costs for mother-infant pairs (SOC: $50, MCH-ART: $69). Outcomes included pediatric HIV infections, maternal and infant life expectancy (LE), lifetime HIV-related per-person costs, and incremental cost-effectiveness ratios (ICERs; ICER
Results: Compared to SOC, MCH-ART increased maternal LE (SOC: 25.26 years, MCH-ART: 26.20 years) and lifetime costs (SOC: $9,912, MCH-ART: $10,207; discounted). Projected pediatric outcomes for all HIV-exposed children were similar between arms, although undiscounted LE for HIV-infected children was shorter in SOC (SOC: 23.13 years, MCH-ART: 23.40 years). Combining discounted maternal and pediatric outcomes, the ICER was $599/YLS.

Conclusion: Co-located maternal HIV and pediatric care, integrated in MCH services throughout breastfeeding, is a cost-effective strategy to improve maternal and pediatric outcomes and should be implemented in South Africa.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225104PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857940PMC
March 2020

Shortened Tuberculosis Treatment for People with HIV in South Africa. A Model-based Evaluation and Cost-effectiveness Analysis.

Ann Am Thorac Soc 2020 02;17(2):202-211

Medical Practice Evaluation Center.

Recent tuberculosis treatment trials failed to show that some 4-month (4m) regimens were noninferior to conventional 6-month (6m) regimens for a composite clinical outcome. Novel shortened regimens may still have important clinical and economic benefits in populations with high loss to follow-up (LTFU) and in subgroups such as people with human immunodeficiency virus. To identify scenarios in which a novel 4m regimen would be preferred to a conventional 6m regimen for treatment of drug-susceptible tuberculosis in people with human immunodeficiency virus in South Africa, in terms of short-term and long-term clinical and economic outcomes. We used the Cost-Effectiveness of Preventing AIDS Complications-International microsimulation model to project outcomes modeled on participants in the OFLOTUB trial. For calibration purposes, we did a base case analysis by applying trial-informed parameters for the 4m/6m regimens, including monthly LTFU during treatment (0.68%/0.83%), average monthly tuberculosis recurrence (0.65%/0.31%), and monthly drug costs (U.S. dollars [USD]25.90/3.70). We then evaluated different scenarios and 4m regimen characteristics, varying key parameters, including LTFU (informed by observational cohort data), recurrence, and cost. We projected outcomes, including 2-year mortality and life expectancy. We conducted a cost-effectiveness analysis, evaluating the incremental cost-effectiveness ratio of a 4m versus 6m regimen. In the base case model analysis, risk of the composite unfavorable outcome in the 4m/6m groups was 19.8%/15.9%, similar to the trial; projected life expectancies were 22.1/22.3 years. In analyses of alternative scenarios and 4m regimen characteristics, a 4m regimen yielded lower risk of the composite unfavorable outcome than the conventional 6m regimen if LTFU increased to greater than 3.5%/mo or if average recurrence after a 4m regimen decreased to less than 0.45%/mo, and it yielded higher life expectancy if LTFU was greater than 3.5%/mo or if recurrence was less than 0.5%/mo. A 4m regimen was not cost-effective in the base case but became cost-effective (incremental cost-effectiveness ratio
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http://dx.doi.org/10.1513/AnnalsATS.201905-418OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993794PMC
February 2020

Effect of PEPFAR funding policy change on HIV service delivery in a large HIV care and treatment network in Nigeria.

PLoS One 2019 25;14(9):e0221809. Epub 2019 Sep 25.

Vanderbilt Institute for Global Health, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.

The transition to PEPFAR 2.0 with its focus on country ownership was accompanied by substantial funding cuts. We describe the impact of this transition on HIV care in a large network of HIV clinics in Nigeria. We surveyed 30 comprehensive HIV treatment clinics to assess services supported before (October 2013-September 2014) and after (October 2014-September 2015) the PEPFAR funding policy change, the impact of these policy changes on service delivery areas, and response of clinics to the change. We compared differences in support for staffing, laboratory services, and clinical operations pre- and post-policy change using paired t-tests. We used framework analysis to assess answers to open ended questions describing responses to the policy change. Most sites (83%, n = 25) completed the survey. The majority were public (60%, n = 15) and secondary (68%, n = 17) facilities. Clinics had a median of 989 patients in care (IQR: 543-3326). All clinics continued to receive support for first and second line antiretrovirals and CD4 testing after the policy change, while no clinics received support for other routine drug monitoring labs. We found statistically significant reductions in support for viral load testing, staff employment, defaulter tracking, and prevention services (92% vs. 64%, p = 0.02; 80% vs. 20%, 100% vs. 44%, 84% vs. 16%, respectively, p<0.01 for all) after the policy change. Service delivery was hampered by interrupted laboratory services and reduced wages and staff positions leading to reduced provider morale, and compromised quality of care. Almost all sites (96%) introduced user fees to address funding shortages. Clinics in Nigeria are experiencing major challenges in providing routine HIV services as a result of PEPFAR's policy changes. Funding cutbacks have been associated with compromised quality of care, staff shortages, and reliance on fee-based care for historically free services. Sustainable HIV services funding models are urgently needed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221809PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760763PMC
March 2020