A focused multi-state model to estimate the pediatric and adolescent HIV epidemic in Thailand, 2005-2025.

BACKGROUND: We estimated the magnitude of the HIV epidemic among children and youth living with HIV (CYHIV) aged 0-25 years in Thailand, projecting forward from 2005 to 2025, and identified underreported input parameters that influence epidemic projections, in order to inform future public health and research priorities. METHODS: We developed a focused multi-state transition model incorporating perinatally-acquired HIV and non-perinatally-acquired HIV, stratified by population, including men who have sex with men (MSM), female sex workers (FSW), people who inject drugs (PWID), and the remainder of the population ("other"). We populated the model with published and programmatic data from the Thai national AIDS program when available. We projected the period from 2005-2025 and compared model results to programmatic data and projections from other models. In a scenario analysis, we projected the potential impact of pre-exposure prophylaxis (PrEP) for MSM from 2018-2025. RESULTS: The initial 2005 cohort was comprised of 66,900 CYHIV; 8% CYHIV were <5 years, 21% were 5-14 years, and 71% were 15-25 years of age. By 2020, 94% were projected to be >15 years and infections among MSM constituted 83% of all new HIV infections. The numbers of CYHIV decreased over time, projected to reach 30,760 by 2020 (-54%) and 22,640 by 2025 (-66%). The proportion of all CYHIV aged 0-25 who were diagnosed and on ART increased from 37 to 60% over the 2005-2025 period. Projections were sensitive to variations in assumptions about initial HIV prevalence and incidence among MSM, PWID, and "other" youth. CONCLUSIONS: More data on incidence rates among sexual and gender minority youth and PWID are needed to characterize the role of specific exposures and key populations in the adolescent HIV epidemic. More accurate estimates will project shifts in population and inform more targeted interventions to prevent and care for Thai CYHIV.

Mortality among US veterans after emergency visits to Veterans Affairs and other hospitals: retrospective cohort study.

OBJECTIVE: To measure and compare mortality outcomes between dually eligible veterans transported by ambulance to a Veterans Affairs hospital and those transported to a non-Veterans Affairs hospital. DESIGN: Retrospective cohort study using data from medical charts and administrative files. SETTING: Emergency visits by ambulance to 140 Veteran Affairs and 2622 non-Veteran Affairs hospitals across 46 US states and the District of Columbia in 2001-18. PARTICIPANTS: National cohort of 583 248 veterans (aged ≥65 years) enrolled in both the Veterans Health Administration and Medicare programs, who resided within 20 miles of at least one Veterans Affairs hospital and at least one non-Veterans Affairs hospital, in areas where ambulances regularly transported patients to both types of hospitals. INTERVENTION: Emergency treatment at a Veterans Affairs hospital. MAIN OUTCOME MEASURE: Deaths in the 30 day period after the ambulance ride. Linear probability models of mortality were used, with adjustment for patients' demographic characteristics, residential zip codes, comorbid conditions, and other variables. RESULTS: Of 1 470 157 ambulance rides, 231 611 (15.8%) went to Veterans Affairs hospitals and 1 238 546 (84.2%) went to non-Veterans Affairs hospitals. The adjusted mortality rate at 30 days was 20.1% lower among patients taken to Veterans Affairs hospitals than among patients taken to non-Veterans Affairs hospitals (9.32 deaths per 100 patients (95% confidence interval 9.15 to 9.50) v 11.67 (11.58 to 11.76)). The mortality advantage associated with Veterans Affairs hospitals was particularly large for patients who were black (-25.8%), were Hispanic (-22.7%), and had received care at the same hospital in the previous year. CONCLUSIONS: These findings indicate that within a month of being treated with emergency care at Veterans Affairs hospitals, dually eligible veterans had substantially lower risk of death than those treated at non-Veterans Affairs hospitals. The nature of this mortality advantage warrants further investigation, as does its generalizability to other types of patients and care. Nonetheless, the finding is relevant to assessments of the merit of policies that encourage private healthcare alternatives for veterans.

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

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.

The Cost-effectiveness of Human Immunodeficiency Virus (HIV) Preexposure Prophylaxis and HIV Testing Strategies in High-risk Groups in India.

BACKGROUND: The human immunodeficiency virus (HIV) epidemic in India is concentrated among 3.1 million men who have sex with men (MSM) and 1.1 million people who inject drugs (PWID), with a mean incidence of 0.9-1.4 per 100 person-years. We examined the cost-effectiveness of both preexposure prophylaxis (PrEP) and HIV testing strategies for MSM and PWID in India. METHODS: We populated an HIV microsimulation model with India-specific data and projected clinical and economic outcomes of 7 strategies for MSM/PWID, including status quo; a 1-time HIV test; routine HIV testing every 3, 6, or 12 months; and PrEP with HIV testing every 3 or 6 months. We used a willingness-to-pay threshold of US$1950, the 2017 Indian per capita gross domestic product, to define cost-effectiveness. RESULTS: HIV testing alone increased life expectancy by 0.07-0.30 years in MSM; PrEP added approximately 0.90 life-years to status quo. Results were similar in PWID. PrEP with 6-month testing was cost-effective for both MSM (incremental cost-effectiveness ratio [ICER], $1000/year of life saved [YLS]) and PWID (ICER, $500/YLS). Results were most sensitive to HIV incidence. PrEP with 6-month testing would increase HIV-related expenditures by US$708 million (MSM) and US$218 million (PWID) over 5 years compared to status quo. CONCLUSIONS: While the World Health Organization recommends PrEP with quarterly HIV testing, our analysis identifies PrEP with semiannual testing as the cost-effective HIV prevention strategy for Indian MSM and PWID. Since nationwide scale-up would require a substantial fiscal investment, areas of highest HIV incidence may be the appropriate initial targets for PrEP scale-up.

The Costs of Drugs in Infectious Diseases: Branded, Generics, and Why We Should Care.

While health care providers have largely turned a blind eye, the cost of health care in the US has been skyrocketing, in part as a result of rising drug prices. Patent protections and market exclusivity, while serving to incentivize targeted new drug development, have exacerbated inequitable outcomes and reduced access, sometimes fueling national epidemics. Branded drug manufacturers face few barriers to exorbitant pricing of drugs with exclusivity-as in the cases of Sovaldi, Zyvox, and Truvada. Furthermore, albendazole, pyrimethamine, and penicillin demonstrate that generic medications without patent exclusivity are not guaranteed to have durably low costs, especially where manufacturer competition is lacking. There is a way forward: through education and awareness, cost-conscious guideline development, government regulation, and market-level incentives, health care providers can collaborate to contain drug prices, curbing expenditures overall while expanding health care access to patients.

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

Rationale: 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.Objectives: 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.Methods: 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.Results: 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

Cost-effectiveness of urine-based tuberculosis screening in hospitalised patients with HIV in Africa: a microsimulation modelling study.

BACKGROUND: Testing urine improves the number of tuberculosis diagnoses made among patients in hospital with HIV. In conjunction with the two-country randomised Rapid Urine-based Screening for Tuberculosis to Reduce AIDS-related Mortality in Hospitalised Patients in Africa (STAMP) trial, we used a microsimulation model to estimate the effects on clinical outcomes and the cost-effectiveness of adding urine-based tuberculosis screening to sputum screening for hospitalised patients with HIV. METHODS: We compared two tuberculosis screening strategies used irrespective of symptoms among hospitalised patients with HIV in Malawi and South Africa: a GeneXpert assay (Cepheid, Sunnyvale, CA, USA) for Mycobacterium tuberculosis and rifampicin resistance (Xpert) in sputum samples (standard of care) versus sputum Xpert combined with a lateral flow assay for M tuberculosis lipoarabinomannan in urine (Determine TB-LAM Ag test, Abbott, Waltham, MA, USA [formerly Alere]; TB-LAM) and concentrated urine Xpert (intervention). A cohort of simulated patients was modelled using selected characteristics of participants, tuberculosis diagnostic yields, and use of hospital resources in the STAMP trial. We calibrated 2-month model outputs to the STAMP trial results and projected clinical and economic outcomes at 2 years, 5 years, and over a lifetime. We judged the intervention to be cost-effective if the incremental cost-effectiveness ratio (ICER) was less than US$750/year of life saved (YLS) in Malawi and $940/YLS in South Africa. A modified intervention of adding only TB-LAM to the standard of care was also evaluated. We did a budget impact analysis of countrywide implementation of the intervention. FINDINGS: The intervention increased life expectancy by 0·5-1·2 years and was cost-effective, with an ICER of $450/YLS in Malawi and $840/YLS in South Africa. The ICERs decreased over time. At lifetime horizon, the intervention remained cost-effective under nearly all modelled assumptions. The modified intervention was at least as cost-effective as the intervention (ICERs $420/YLS in Malawi and $810/YLS in South Africa). Over 5 years, the intervention would save around 51 000 years of life in Malawi and around 171 000 years of life in South Africa. Health-care expenditure for screened individuals was estimated to increase by $37 million (10·8%) and $261 million (2·8%), respectively. INTERPRETATION: Urine-based tuberculosis screening of all hospitalised patients with HIV could increase life expectancy and be cost-effective in resource-limited settings. Urine TB-LAM is especially attractive because of high incremental diagnostic yield and low additional cost compared with sputum Xpert, making a compelling case for expanding its use to all hospitalised patients with HIV in areas with high HIV burden and endemic tuberculosis. FUNDING: UK Medical Research Council, UK Department for International Development, Wellcome Trust, US National Institutes of Health, Royal College of Physicians, Massachusetts General Hospital.

Staphylococcus aureus colonization in children undergoing heart surgery.

BACKGROUND: Staphylococcus aureus is an important cause of cardiac surgical site infection. Based on studies in adults, nasal screening to detect S aureuscolonization is used to guide decolonization and selection of prophylactic antibiotics. In our Children's Hospital, a sensitive polymerase chain reaction (PCR)-based assay is used to screen patients undergoing cardiac surgery for nasal colonization with methicillin-sensitive S aureus (MSSA) and methicillin-resistant S aureus (MRSA). Additionally for patients in diapers, cultures are used to detect MRSA colonization of the groin. The purpose of this study was to determine whether screening two anatomic locations results in a higher MRSA detection rate among children undergoing cardiac surgery. METHODS: A retrospective chart review determined whether the frequency of bacterial colonization with MRSA differed by anatomic site. Records for 322 pediatric cardiac surgery procedures performed between January 2009 and June 2011 were reviewed. Both a nasal PCR and a second anatomic site culture were performed before 102 procedures. RESULTS: The overall rate of colonization with MRSA and MSSA was 4.2% and 29.1%, respectively. Of the seven dually screened patients who tested positive for MRSA, two were identified solely via a groin test, four by nasal screening alone, and one by both the tests. Screening of only the nose would have failed to detect 28.6% of the MRSA cases. CONCLUSION: Preoperative detection of MRSA colonization may be enhanced by screening both the nose and a second anatomic site. The clinical utility of the extranasal MRSA culture was limited due to the long assay turnaround time.