Geographic Variation in Qualified Health Plan Coverage and Prior Authorization Requirements for HIV Preexposure Prophylaxis.

Importance: HIV preexposure prophylaxis (PrEP) is a key component of the Ending the HIV Epidemic (EHE) Initiative to curb new HIV diagnoses. In October 2019, emtricitabine/tenofovir alafenamide was added as an approved formulation for PrEP in addition to emtricitabine/tenofovir disoproxil fumarate; despite availability of another formulation with a similar prevention indication, variations in coverage may limit access. Objective: To assess qualified health plan (QHP) coverage, prior authorization (PA) requirements, and specialty tiering for emtricitabine/tenofovir disoproxil fumarate and emtricitabine/tenofovir alafenamide following emtricitabine/tenofovir alafenamide approval as a PrEP treatment. Design, Setting, and Participants: This cross-sectional study analyzed QHPs in the US that were compliant with the Patient Protection and Affordable Care Act from 2018 to 2020. QHPs were categorized by region and EHE priority jurisdictions. Data analysis occurred from March 2022 to March 2023. Exposures: Enrollment in a qualified health plan certified by the Patient Protection and Affordable Care Act. Main Outcome and Measures: Annual variation in QHP coverage and PA requirement for emtricitabine/tenofovir disoproxil fumarate and/or emtricitabine/tenofovir alafenamide. Descriptive statistics were reported for all outcomes. A secondary outcome was whether the PrEP formulation was determined by the QHP to be placed on a specialty drug tier. Results: A total of 58 087 QHPs (19 533 for 2018; 17 007 for 2019; and 21 547 for 2020) were analyzed. QHPs covered emtricitabine/tenofovir disoproxil fumarate (19 165 QHPs [98.1%] in 2018; 16 970 QHPs [99.8%] in 2019; 20 045 QHPs [94.8%] in 2020) at a higher rate than emtricitabine/tenofovir alafenamide (17 391 QHPs [91.9%] in 2018; 15 757 QHPs [92.7%] in 2019; 18 836 QHPs [87.4%] in 2020). QHPs in the South required exclusive PA (ie, PA for 1 of the formulations even if the QHP covered both) for emtricitabine/tenofovir disoproxil fumarate and emtricitabine/tenofovir alafenamide at the highest rates in all 3 years. In the South, the rate of PA for emtricitabine/tenofovir disoproxil fumarate increased from 806 of 8023 QHPs (10.0%) in 2018 to 3466 of 7401 QHPs (46.8%) in 2020. QHPs with exclusive PA requirement for emtricitabine/tenofovir disoproxil fumarate were higher in EHE jurisdictions than non-EHE jurisdictions (difference: 2018, 0.9 percentage points; 2019, 3.5 percentage points; 2020, 29.1 percentage points). QHPs were more likely to place emtricitabine/tenofovir disoproxil fumarate on a specialty tier compared with emtricitabine/tenofovir alafenamide (difference: 2018, 1.8 percentage points; 2019, 3.7 percentage points; 2020, 4.1 percentage points). Conclusions and Relevance: In this cross-sectional study, despite similar indications for biomedical prevention, QHPs were more likely to cover emtricitabine/tenofovir disoproxil fumarate than emtricitabine/tenofovir alafenamide, and QHPs were also more likely to subject emtricitabine/tenofovir disoproxil fumarate to PA or place it on a specialty tier despite the broader clinical indication. QHP PA requirements of emtricitabine/tenofovir disoproxil fumarate following emtricitabine/tenofovir alafenamide approval does not reflect clinical guidelines. The requirements could reflect differences in clinical indication, manufacturer discounts, or anticipation of a changing regulations and emerging generics. High rates of exclusive PA for emtricitabine/tenofovir disoproxil fumarate in areas where rates of HIV diagnoses are highest and PrEP is most needed (eg, the South and EHE priority jurisdictions) is concerning; policy solutions to address the growing PrEP health equity crisis could include regulator actions and a national PrEP program.

Could a Shigella vaccine impact long-term health outcomes?: Summary report of an expert meeting to inform a Shigella vaccine public health value proposition, March 24 and 29, 2021.

Shigellosis is a leading cause of diarrhea and dysentery in young children from low to middle-income countries and adults experiencing traveler's diarrhea worldwide. In addition to acute illness, infection by Shigella bacteria is associated with stunted growth among children, which has been linked to detrimental long-term health, developmental, and economic outcomes. On March 24 and 29, 2021, PATH convened an expert panel to discuss the potential impact of Shigella vaccines on these long-term outcomes. Based on current empirical evidence, this discussion focused on whether Shigella vaccines could potentially alleviate the long-term burden associated with Shigella infections. Also, the experts provided recommendations about how to best model the burden, health and vaccine impact, and economic consequences of Shigella infections. This international multidisciplinary panel included 13 scientists, physicians, and economists from multiple relevant specialties. According to the panel, while the relationship between Shigella infections and childhood growth deficits is complex, this relationship likely exists. Vaccine probe studies are the crucial next step to determine whether vaccination could ameliorate Shigella infection-related long-term impacts. Infants should be vaccinated during their first year of life to maximize their protection from severe acute health outcomes and ideally reduce stunting risk and subsequent negative long-term developmental and health impacts. With vaccine schedule crowding, targeted or combination vaccination approaches would likely increase vaccine uptake in high-burden areas. Shigella impact and economic assessment models should include a wider range of linear growth outcomes. Also, these models should produce a spectrum of results-ones addressing immediate benefits for usual health care decision-makers and others that include broader health impacts, providing a more comprehensive picture of vaccination benefits. While many of the underlying mechanisms of this relationship need better characterization, the remaining gaps can be best addressed by collecting data post-vaccine introduction or through large trials.

Worsening Disparities in State-Level Uptake of Human Immunodeficiency Virus Preexposure Prophylaxis, 2014-2018.

Retrospective analysis of human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) use among individuals with PrEP indications demonstrates worsening disparities in uptake between early- and late-adopting states from 2014 to 2018. To end the HIV epidemic, federal and state governments must close gaps by translating successful policies from early-adopting states to late-adopting states.

Assessment of Seroprevalence of SARS-CoV-2 and Risk Factors Associated With COVID-19 Infection Among Outpatients in Virginia.

Importance: Data from seroepidemiologic surveys measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure in diverse communities and ascertaining risk factors associated with infection are important to guide future prevention strategies. Objective: To assess the prevalence of previous SARS-CoV-2 infection across Virginia and the risk factors associated with infection after the first wave of coronavirus disease 2019 (COVID-19) infections in the US. Design, Setting, and Participants: In this statewide cross-sectional surveillance study, 4675 adult outpatients presenting for health care not associated with COVID-19 in Virginia between June 1 and August 14, 2020, were recruited to participate in a questionnaire and receive venipuncture to assess SARS-CoV-2 serology. Eligibility was stratified to meet age, race, and ethnicity quotas that matched regional demographic profiles. Main Outcomes and Measures: The main outcome was SARS-CoV-2 seropositivity, as measured by the Abbott SARS-CoV-2 immunoglobulin G assay. Results: Among 4675 adult outpatients (mean [SD] age, 48.8 [16.9] years; 3119 women [66.7%]; 3098 White [66.3%] and 4279 non-Hispanic [91.5%] individuals) presenting for non-COVID-19-associated health care across Virginia, the weighted seroprevalence was 2.4% (95% CI, 1.8%-3.1%) and ranged from 0% to 20% by zip code. Seroprevalence was notably higher among participants who were Hispanic (10.2%; 95% CI, 6.1%-14.3%), residing in the northern region (4.4%; 95% CI, 2.8%-6.1%), aged 40 to 49 years (4.4%; 95% CI, 1.8%-7.1%), and uninsured (5.9%; 95% CI, 1.5%-10.3%). Higher seroprevalence was associated with Hispanic ethnicity (adjusted odds ratio [aOR], 3.56; 95% CI, 1.76-7.21), residence in a multifamily unit (aOR, 2.55; 95% CI, 1.25-5.22), and contact with an individual with confirmed COVID-19 infection (aOR, 4.33; 95% CI, 1.77-10.58). The sensitivity of serology results was 94% (95% CI, 70%-100%) among those who reported receiving a previous polymerase chain reaction test for COVID-19 infection. Among 101 participants with seropositive results, 67 individuals (66.3%) were estimated to have asymptomatic infection. These data suggested a total estimated COVID-19 burden that was 2.8-fold higher than that ascertained by PCR-positive case counts. Conclusions and Relevance: This large statewide serologic study estimated that 2.4% of adults in Virginia had exposure to SARS-CoV-2, which was 2.8-fold higher than confirmed case counts. Hispanic ethnicity, residence in a multifamily unit, and contact with an individual with confirmed COVID-19 infection were significant risk factors associated with exposure. Most infections were asymptomatic. As of August 2020, the population in Virginia remained largely immunologically naive to the virus.

Impact of Low-Cost Point-of-Use Water Treatment Technologies on Enteric Infections and Growth among Children in Limpopo, South Africa.

Enteric infections early in life have been associated with poor linear growth among children in low-resource settings. Point-of-use water treatment technologies provide effective and low-cost solutions to reduce exposure to enteropathogens from drinking water, but it is unknown whether the use of these technologies translates to improvements in child growth. We conducted a community-based randomized controlled trial of two water treatment technologies to estimate their effects on child growth in Limpopo, South Africa. We randomized 404 households with a child younger than 3 years to receive a silver-impregnated ceramic water filter, a silver-impregnated ceramic tablet, a safe-storage water container alone, or no intervention, and these households were followed up quarterly for 2 years. We estimated the effects of the interventions on linear and ponderal growth, enteric infections assessed by quantitative molecular diagnostics, and diarrhea prevalence. The silver-impregnated ceramic water filters and tablets consistently achieved approximately 1.2 and 3 log reductions, respectively, in total coliform bacteria in drinking water samples. However, the filters and tablets were not associated with differences in height (height-for-age z-score differences compared with no intervention: 0.06, 95% CI: -0.29, 0.40, and 0.00, 95% CI: -0.35, 0.35, respectively). There were also no effects of the interventions on weight, diarrhea prevalence, or enteric infections. Despite their effectiveness in treating drinking water, the use of the silver-impregnated ceramic water filters and tablets did not reduce enteric infections or improve child growth. More transformative water, sanitation, and hygiene interventions that better prevent enteric infections are likely needed to improve long-term child growth outcomes.

Regional Disparities in Qualified Health Plans' Prior Authorization Requirements for HIV Pre-exposure Prophylaxis in the United States.

Importance: With the goal of ending the HIV epidemic in the United States, access to HIV pre-exposure prophylaxis (PrEP) is essential to help curb new HIV infections. There has been differential uptake of PrEP by region, with the South lagging behind other regions. Discriminatory benefit design (benefit design that prevents or delays people with complex or expensive conditions from obtaining appropriate treatment) through prior authorization requirements could be a systemic barrier that contributes to the decreased PrEP uptake in the South. Objectives: To investigate whether there are regional disparities in prior authorization requirements for combined tenofovir disoproxil fumarate and emtricitabine for qualified health plans (QHPs) and to assess whether any QHP characteristics explain the disparities. Design, Setting, and Participants: This design was a cross-sectional study of QHPs offered in the 2019 Affordable Care Act Marketplace. The QHPs studied included all Affordable Care Act-compliant individual and small-group market plans in the United States. Exposures: The primary exposure was the 4 census regions (Northeast, West, Midwest, and South). Additional covariates included other plan characteristics. Main Outcomes and Measures: Prior authorization requirement for combined tenofovir disoproxil fumarate and emtricitabine at the QHP level. Results: In total, 16 853 QHPs were analyzed (18.2% in the Northeast, 19.5% in the West, 25.0% in the Midwest, and 37.3% in the South). Overall, 18.9% of QHPs required prior authorization for combined tenofovir disoproxil fumarate and emtricitabine. This percentage varied by region, with 2.3%, 6.2%, 13.3%, and 37.3% of plans requiring prior authorization in the Northeast, West, Midwest, and South, respectively. Compared with QHPs in the Northeast, QHPs in the South were 15.89 (95% CI, 12.57-20.09) times as likely to require prior authorization, whereas the Midwest and West were 5.69 (95% CI, 4.45-7.27) and 2.65 (95% CI, 2.02-3.47) times as likely, respectively. Other plan characteristics did not account for the regional variation. Conclusions and Relevance: Compared with QHPs in the Northeast, QHPs in the South were almost 16 times as likely to require prior authorization for PrEP, and the reasons for these disparities are unknown. The prior authorization requirement is a possible barrier to PrEP access in the South, which is the region of the United States with the most annual new HIV diagnoses. There is limited regulation of QHPs' prior authorization requirements. Federal- or state-level health policy laws may be necessary to remove this system-level barrier to ending the HIV epidemic in the United States.

Cost-Effectiveness of Postoperative Drug Rehabilitation for Injection Drug Users.

BACKGROUND: With the opioid crisis showing no sign of abating, strategies are needed to facilitate postoperative care for endocarditis related to injection drug use (IDU). The current standard, 6 weeks of intravenous antibiotics, yields frequent reoperation and IDU relapse. We examined the cost-effectiveness of inpatient drug rehabilitation (DR) postoperatively to optimize outcomes and costs. METHODS: Two postoperative strategies were assessed: hospital-only care (HC) vs HC plus inpatient DR. Monte Carlo simulation evaluated effectiveness in quality-adjusted life-years (QALY) and cost per patient calculated over a 20-year time horizon in 100,000 iterations. Willingness to pay was set to $100,000/QALY. To determine probabilities of continued postoperative IDU, recurrent infection, and death, best available evidence was combined with institutional data from IDU patients. Baseline probability of postoperative IDU was set to 35% after DR vs 60% after HC, and the cost of inpatient rehabilitation to $30,000. RESULTS: Addition of inpatient DR to standard HC is the favorable strategy, with incremental per-patient cost of $36,920 and 0.93 QALYs gained over 20 years. Sensitivity analysis demonstrates DR is within our willingness-to-pay of $100,000/QALY if postoperative IDU is reduced by at least 7% (from 60% to 53%). CONCLUSIONS: Addition of postoperative inpatient DR for IDU-related endocarditis is cost-effective even if only a modest reduction in IDU is achieved. Collaboration between hospitals and payors to launch pilot programs that provide postoperative addiction treatment and intravenous antibiotics after cardiac operations could dramatically improve endocarditis care.

Evidence From a Multistate Cohort: Enrollment in Affordable Care Act Qualified Health Plans' Association With Viral Suppression.

BACKGROUND: Healthcare delivery changes associated with viral suppression (VS) could contribute to the United States' "Ending the HIV Epidemic" (EtHE) initiative. This study aims to determine whether Qualified Health Plans (QHPs) purchased by AIDS Drug Assistance Programs (ADAPs) are associated with VS for low-income people living with HIV (PLWH) across 3 states. METHODS: A multistate cohort of ADAP clients eligible for ADAP-funded QHPs were studied (2014-2015). A log-binomial model was used to estimate the association of demographics and healthcare delivery factors with QHP enrollment prevalence and 1-year risk of VS. A number needed to treat/enroll (NNT) for 1 additional person to achieve viral suppression was calculated. RESULTS: Of the cohort (n = 7776), 52% enrolled in QHPs. QHP enrollment in 2015 was associated with QHP coverage in 2014 (adjusted PR [aPR], 3.28; 95% confidence intervals [CIs], 3.06-3.53) and engagement in care in 2014 (aPR, 1.16; 1.04-1.28). PLWH who were engaged in care (n = 4597) and had QHPs had a higher VS rate than those who received medications from Direct ADAP (86.0% vs 80.2%). QHPs' NNT for an additional person to achieve VS is 20 (14.1-34.5). Starting undetectable (adjusted risk ratio [aRR], 1.39; 1.28-1.52) and enrolling in QHPs in 2015 (aRR, 1.06; 0.99-1.14) was associated with VS. CONCLUSIONS: Once enrolled in ADAP-funded QHPs, ADAP clients stay enrolled. Enrollment is associated with VS across states/demographic groups. ADAPs, especially in the South and in Medicaid nonexpansion states, should consider investing in QHPs because increased enrollment could improve VS rates. This evidence-based intervention could be part of EtHE.

Longitudinal Assessment of Antibiotic Resistance in Fecal Escherichia coli in Tanzanian Children.

Antibiotic-resistant bacterial infections are a major public health problem, and children in low-resource settings represent a particularly high-risk group. Few data are available on the dynamics of and risk factors for gastrointestinal carriage of antibiotic-resistant bacteria in these vulnerable populations. In this study, we described the antibiotic susceptibility profiles of Escherichia coli isolated from stool specimens collected from children aged 6 to 60 months enrolled in a birth cohort study in Haydom, Tanzania. We estimated the association between sociodemographic risk factors, child illnesses, and antibiotic exposure and E. coli drug resistance. Carriage of antibiotic-resistant E. coli was common starting early in life and did not clearly increase with age. The majority of isolates were resistant to ampicillin (749/837; 89.5%), cefazolin (742/837; 88.6%), and cotrimoxazole (721/837; 86.1%). Resistance to amoxicillin/clavulanate (361/836; 43.2%), ampicillin/sulbactam (178/819; 21.7%), nalidixic acid (131/831; 15.8%), and azithromycin (115/837; 13.7%) was also seen. Only 1.8% (15/837) of the pooled E. coli isolates met the criteria for extended-spectrum beta-lactamase production. High antibiotic use (0.26 additional resistant antibiotic classes; 95% CI: 0.05, 0.47) and high income (0.28 additional resistant antibiotic classes; 95% CI: 0.06, 0.50) were associated with the carriage of antibiotic-resistant E. coli, whereas hospital birth, crowding in the home, improved drinking water and sanitation, and common childhood illnesses were not. In this setting, the carriage of antibiotic-resistant E. coli was common. Other than recent antibiotic exposure and high income, individual risk factors for the acquisition and carriage of resistance could not be identified, suggesting that population-level interventions are needed.

Rising rates of injection drug use associated infective endocarditis in Virginia with missed opportunities for addiction treatment referral: a retrospective cohort study.

BACKGROUND: Injection drug use (IDU) is a growing public health threat in Virginia, though there is limited knowledge of related morbidity. The purpose of this study was to describe the temporal, geographic and clinical trends and characteristics of infective endocarditis associated with IDU (IDU-IE) and to identify opportunities for better-quality care of people who inject drugs (PWID). METHODS: We reviewed charts for all admissions coded for both IE and drug use disorders at the University of Virginia Medical Center (UVA) from January 2000 to July 2016. A random sample of 30 admissions coded for IE per year were reviewed to evaluate temporal trends in the proportion of IDU associated IE cases. RESULTS: There were a total of 76 patients with IDU-IE during the study period, 7.54-fold increase (prevalence ratio: 8.54, 95% CI 3.70-19.72) from 2000 to 2016. The proportion of IE that was IDU-associated increased by nearly 10% each year (prevalence ratio of IDU per year: 1.09, 95% CI: 1.05-1.14). Patients with IDU-IE had longer hospital stays [median days (interquartile range); IDU-IE, 17 (10-29); non-IDU-IE, 10 (6-18); p-value = 0.001] with almost twice the cost of admission as those without IDU [median (interquartile range); IDU-IE, $47,899 ($24,578-78,144); non-IDU-IE, $26,460 ($10,220-60,059); p-value = 0.001]. In 52% of cases there was no documentation of any discussion regarding addiction treatment. CONCLUSION: IDU-IE is a severe infection that leads to significant morbidity and healthcare related costs. IDU-IE rates are increasing and will likely continue to do so without targeted interventions to help PWID. The diagnosis and treatment of IDU-IE provides an opportunity for the delivery of addiction treatment, counseling, and harm reduction strategies.