The Clinical Impact and Cost-effectiveness of Measles-Mumps-Rubella Vaccination to Prevent Measles Importations Among International Travelers From the United States.

BACKGROUND: Measles importations and the subsequent spread from US travelers returning from abroad are responsible for most measles cases in the United States. Increasing measles-mumps-rubella (MMR) vaccination among departing US travelers could reduce the clinical impact and costs of measles in the United States. METHODS: We designed a decision tree to evaluate MMR vaccination at a pretravel health encounter (PHE), compared with no encounter. We derived input parameters from Global TravEpiNet data and literature. We quantified Riskexposure to measles while traveling and the average number of US-acquired cases and contacts due to a measles importation. In sensitivity analyses, we examined the impact of destination-specific Riskexposure, including hot spots with active measles outbreaks; the percentage of previously-unvaccinated travelers; and the percentage of travelers returning to US communities with heterogeneous MMR coverage. RESULTS: The no-encounter strategy projected 22 imported and 66 US-acquired measles cases, costing $14.8M per 10M travelers. The PHE strategy projected 15 imported and 35 US-acquired cases at $190.3M per 10M travelers. PHE was not cost effective for all international travelers (incremental cost-effectiveness ratio [ICER] $4.6M/measles case averted), but offered better value (ICER <$100 000/measles case averted) or was even cost saving for travelers to hot spots, especially if travelers were previously unvaccinated or returning to US communities with heterogeneous MMR coverage. CONCLUSIONS: PHEs that improve MMR vaccination among US international travelers could reduce measles cases, but are costly. The best value is for travelers with a high likelihood of measles exposure, especially if the travelers are previously unvaccinated or will return to US communities with heterogeneous MMR coverage.

Should We Be Testing for Baseline Integrase Resistance in Patients Newly Diagnosed With Human Immunodeficiency Virus?

Background: Current guidelines recommend genotype resistance testing at diagnosis to guide initial selection of antiretroviral therapy (ART). Many standard resistance genotypes exclude testing for resistance to integrase inhibitors ("IR testing"), although this class of drugs is a component of most recommended first-line regimens. Methods: We compared the 96-week clinical outcomes and cost-effectiveness of 2 strategies: no IR testing vs IR testing performed at human immunodeficiency virus (HIV) diagnosis. The base case prevalence of transmitted integrase strand transfer inhibitor (INSTI)-resistant (INSTI-R) virus is estimated at 0.1%. With no IR testing, all patients start dolutegravir (DTG)-based ART after genotype; 12-week suppression rates are 90% (INSTI-susceptible [INSTI-S] virus) and 35% (INSTI-R virus). Those not suppressed at 12 weeks undergo IR testing; if diagnosed with INSTI-R virus, they change to ritonavir-boosted darunavir (DRV/r)-based ART. With IR testing, all patients are diagnosed with INSTI-S/INSTI-R virus prior to ART initiation and start DTG- or DRV/r-based regimens, respectively. Costs include IR tests (175 US dollars [USD]) and ART (41100-44900 USD/year). We examined the impact of key parameters in sensitivity analyses. Results: IR testing resulted in worse clinical outcomes compared to no IR testing and increased costs by 200 USD/person/year. Prevalence of transmitted INSTI-R virus did not affect the favored strategy. No IR testing remained clinically preferred unless DTG suppression of INSTI-R virus was <20% or 96-week DRV/r suppression was >92%. If quality of life was worse with DRV/r- than DTG-based ART, no IR testing was clinically preferred over an even broader range of parameters. Conclusions: In patients with newly diagnosed HIV, IR testing is projected to result in worse outcomes and is not cost-effective. Pretreatment assessment for INSTI resistance should not be recommended in treatment guidelines.

Effect of Previous Adverse Reproductive Health Outcomes on Young Women's Engagement in a Health Coaching Intervention to Improve Contraceptive Continuation.

STUDY OBJECTIVE: Nonadherence in sexual risk reduction interventions might be common among adolescents. We compared intervention completion rates among adolescent and young adult women with and without a previous pregnancy or sexually transmitted infection (STI) participating in a program to improve contraceptive continuation. DESIGN: Secondary data analysis from a feasibility study of a health-coaching intervention to improve contraceptive continuation. SETTING: Three urban pediatric clinics in Philadelphia. PARTICIPANTS: Women ages 14-22 years who were English-speaking, sexually active in the past year, not desiring pregnancy in the next year, and starting a new contraceptive method. INTERVENTIONS: At baseline, participants completed a sociodemographic questionnaire and semistructured interview, followed by 5 monthly coaching sessions. Interviews and coaching sessions were audio-recorded, transcribed, and coded for thematic content. MAIN OUTCOME MEASURES: Intervention completion was defined as the number of completed coaching sessions. Secondary outcomes were qualitatively explored group differences in reproductive knowledge, attitudes, and risk perception. RESULTS: Participants with a previous adverse outcome (a previous STI and/or a previous pregnancy) completed fewer coaching sessions than those without such history (median: 2 vs 4; P = .03). Both groups had low HIV/STI knowledge, negative attitudes toward pregnancy, and low HIV/STI risk perception. Those with a previous adverse reproductive outcome held more negative attitudes toward condoms. CONCLUSION: Despite similar reproductive knowledge, attitudes, and risk perception, young women who have experienced an adverse reproductive outcome might be less likely to fully engage in sexual risk reduction interventions. Future studies should confirm these findings and consider strategies to optimize the intervention's reach for vulnerable youth.

Identifying Opportunities to Discuss Pre-Exposure Prophylaxis During Contraceptive Coaching Discussions With Urban Adolescent Women.

PURPOSE: HIV pre-exposure prophylaxis (PrEP) reduces HIV transmission and is approved for adolescents aged 12-17 years. Adolescent girls and young women (AGYW) have modest PrEP uptake rates, while many receive reproductive health counseling. We sought to identify opportunities for incorporating PrEP education in contraceptive counseling delivered to AGYW. METHODS: We performed a secondary analysis of data from the Health Coaching for Contraceptive Continuation pilot study, which supported contraceptive use among AGYW. Participants were 14-22 years old, sexually active with males, and not desiring pregnancy within 12 months. Coaches were sexual health educators with ≥5 years' experience providing contraceptive and PrEP counseling to youth. Participants completed a baseline visit within 30 days of contraceptive initiation and completed up to five monthly coaching sessions. Of 33 enrollees, this analysis includes the 21 who completed ≥4 sessions. Two coders deductively coded session transcripts for five themes: opportunities to discuss PrEP; HIV knowledge, risk perception, and testing attitudes; changes in HIV risk status; condom use knowledge and skills; and sexually transmitted infection knowledge and risk perception. RESULTS: Of the 111 transcripts coded, 24 contained opportunities to discuss PrEP and were inductively analyzed. Thematic analysis demonstrated three types of opportunities for PrEP discussions: failure to introduce information, and provision of incomplete information or misinformation. Analysis also revealed four opportunity contexts: sexually transmitted infection prevention strategies, HIV risk reduction, avoidance of adverse sexual health outcomes, and disclosures of condom nonprotected sexual behaviors. Only one transcript mentioned PrEP. CONCLUSIONS: Multiple opportunities to introduce PrEP counseling exist within contraceptive counseling provided to AGYW.

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

Development and Validation of PREDICT-DM: A New Microsimulation Model to Project and Evaluate Complications and Treatments of Type 2 Diabetes Mellitus.

Background: Type 2 diabetes mellitus (T2DM) affects ∼30 million people in the United States and ∼400 million people worldwide, numbers likely to increase due to the rising prevalence of obesity. We sought to design, develop, and validate PREDICT-DM (PRojection and Evaluation of Disease Interventions, Complications, and Treatments-Diabetes Mellitus), a state-transition microsimulation model of T2DM, incorporating recent data. Methods: PREDICT-DM is populated with natural history, risk factor, and outcome data from large-scale cohort studies and randomized clinical trials. The model projects diabetes-relevant outcomes, including cardiovascular and renal disease outcomes, and 5/10-year survival. We assessed the model validity against 62 endpoints from ACCORD (Action to Control Cardiovascular Risk in Diabetes), VADT (Veterans Affairs Diabetes Trial), and Look AHEAD trials via several comparative statistical methods, including mean absolute percentage error (MAPE), Bland-Altman graphs, and Kaplan-Meier curves. Results: For the comparison between simulated and observed outcomes of the intervention/control arms of the trial, the MAPE was 19%/25% (ACCORD), 29%/20% (VADT), and 42%/10% (Look AHEAD). The Bland-Altman's 95% limit of agreement was 0.02 (ACCORD), 0.03 (VADT), and 0.01 (Look AHEAD), and the mean difference (95% confidence interval) for the comparison between PREDICT-DM and trial endpoints was 0.0025 (-0.0018 to 0.0070) for ACCORD, -0.0067 (-0.0137 to 0.0002) for VADT, and -0.0033 (-0.0067 to 0.00002) for Look AHEAD, indicating an adequate model fit to the data. The model-driven Kaplan-Meier curves were similarly close to those previously published. Conclusions: PREDICT-DM can reasonably predict clinical outcomes from ACCORD and other clinical trials of U.S. patients with T2DM. This model may be leveraged to inform clinical strategy questions related to the management and care of T2DM in the United States.