HIV Preexposure Prophylaxis With Emtricitabine and Tenofovir Disoproxil Fumarate Among Cisgender Women.

Importance: Emtricitabine and tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP) is highly effective in cisgender men who have sex with men (MSM) when adherence is high (>4 doses/week). Real-world effectiveness and adherence with F/TDF for PrEP in cisgender women is less well characterized. Objective: To characterize the effectiveness of F/TDF for PrEP and its relationship with adherence in cisgender women. Design, Setting, and Participants: Data were pooled from 11 F/TDF PrEP postapproval studies conducted in 6 countries that included 6296 cisgender women aged 15 to 69 years conducted from 2012 to 2020. HIV incidence was evaluated according to adherence level measured objectively (tenofovir diphosphate concentration in dried blood spots or tenofovir concentration in plasma; n = 288) and subjectively (electronic pill cap monitoring, pill counts, self-report, and study-reported adherence scale; n = 2954) using group-based trajectory modeling. Exposures: F/TDF prescribed orally once a day. HIV incidence was analyzed in subgroups based on adherence trajectory. Main Outcomes and Measures: HIV incidence. Results: Of the 6296 participants, 46% were from Kenya, 28% were from South Africa, 21% were from India, 2.9% were from Uganda, 1.6% were from Botswana, and 0.8% were from the US. The mean (SD) age at PrEP initiation across all studies was 25 (7) years, with 61% of participants being younger than 25 years. The overall HIV incidence was 0.72 per 100 person-years (95% CI, 0.51-1.01; 32 incident HIV diagnoses among 6296 participants). Four distinct groups of adherence trajectories were identified: consistently daily (7 doses/week), consistently high (4-6 doses/week), high but declining (from a mean of 4-6 doses/week and then declining), and consistently low (less than 2 doses/week). None of the 498 women with consistently daily adherence acquired HIV. Only 1 of the 658 women with consistently high adherence acquired HIV (incidence rate, 0.13/100 person-years [95% CI, 0.02-0.92]). The incidence rate was 0.49 per 100 person-years (95% CI, 0.22-1.08) in the high but declining adherence group (n = 1166) and 1.27 per 100 person-years (95% CI, 0.53-3.04) in the consistently low adherence group (n = 632). Conclusions and Relevance: In a pooled analysis of 11 postapproval studies of F/TDF for PrEP among cisgender women, overall HIV incidence was 0.72 per 100 person-years; individuals with consistently daily or consistently high adherence (4-6 doses/week) to PrEP experienced very low HIV incidence.

HIV-1 Incidence, Adherence, and Drug Resistance in Individuals Taking Daily Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 Pre-Exposure Prophylaxis: Pooled Analysis From 72 Global Studies.

BACKGROUND: Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings. METHODS: HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentration in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies. RESULTS: Among 17,274 participants, there were 101 cases with new HIV-1 diagnosis (0.77 per 100 person-years; 95% CI 0.63-0.94). In 78 cases with resistance data, 18 (23%) had M184I or V, one (1.3%) had K65R, and three (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of <2, 2-3, 4-6, and ≥7 doses/week, respectively, and the corresponding incidence was 3.9 (95% CI 2.9-5.3), 0.24 (0.060-0.95), 0.27 (0.12-0.60), and 0.054 (0.008-0.38) per 100 person-years. Adherence was low in younger participants, Hispanic/Latinx and Black participants, cisgender women, and transgender women. Bone and renal adverse event incidence rates were 0.69 and 11.8 per 100 person-years, respectively, consistent with previous reports. CONCLUSIONS: Leveraging the largest pooled analysis of global PrEP studies to date, we demonstrate that F/TDF is safe and highly effective, even with less than daily dosing, in diverse clinical settings, geographies, populations, and routes of HIV-1 exposure.

Prescription Opioid Exposure During Pregnancy and Risk of Spontaneous Preterm Delivery.

Importance: Opioid exposure during pregnancy has been associated with preterm birth, but prior studies have not differentiated between spontaneous and indicated preterm birth or fully investigated these associations as functions of opioid dose. Objective: To determine whether prescription opioid use during pregnancy is associated with spontaneous preterm birth and whether the association is dose-dependent. Design, Setting, and Participants: This case-control study examined a retrospective cohort of pregnant patients enrolled in Tennessee Medicaid. Enrollment files were linked to health care encounters, hospital discharge information, birth certificate data, and prescription fills. Eligible participants were pregnant people ages 15 to 44 years without opioid use disorder who experienced birth of a single fetus at 24 weeks gestation or greater between 2007 and 2019 with linked birth certificate data. Cases of spontaneous preterm birth were matched with up to 10 controls based on pregnancy start date, race, ethnicity, age at delivery within 2 years, and history of prior preterm birth. Cases and matched controls were continuously enrolled in TennCare for at least 90 days prior to the index date (case delivery date). Exposure: Total opioid MME filled during the 60 days prior to the index date. Main Outcomes and Measures: The primary outcome was spontaneous preterm birth determined by a validated algorithm using birth certificate data. Conditional logistic regression was used to estimate the association between spontaneous preterm birth and total opioid morphine milligram equivalents (MME) dispensed, adjusting for parity, prepregnancy body mass index, education level, tobacco use, hepatitis infections, and pain indications. Results: A total of 25 391 cases (median [IQR] age, 23 [20-28] years; 127 Asian [0.5%], 9820 Black [38.7%], 664 Hispanic [2.6%]; 14 748 non-Hispanic White [58.1%]) with spontaneous preterm birth were identified and matched with 225 696 controls (median [IQR] age, 23 [20-27] years; 229 Asian [0.1%], 89 819 Black [39.8%], 3590 Hispanic [1.6%]; 132 002 non-Hispanic White [58.5%]) (251 087 patients total), with 18 702 patients (7.4%) filling an opioid prescription in the 60 days prior to the index date. Each doubling of nonzero opioid MME was associated with a 4% increase in the odds of spontaneous preterm birth compared with no opioid exposure (adjusted odds ratio, 1.04; 95% CI, 1.01-1.08). Conclusions and Relevance: In this case-control study, a positive association was found between total prescription opioid dose dispensed and the odds of spontaneous preterm birth. These findings support guidance to minimize opioid exposure during pregnancy and prescribe the lowest dose necessary.

Prenatal aneuploidy screening in a low-risk Hispanic population: price elasticity and cost-effectiveness.

BACKGROUND: In October 2015, the Massachusetts Medicaid program temporarily stopped reimbursement for procedures in which the International Classification of Diseases, Tenth Edition, code for serum aneuploidy screening used by certain communities was stipulated. This change led to a substantial number of patients who went without aneuploidy screening for approximately 3 years. OBJECTIVE: This study aimed to determine the change in use and cost-effectiveness of prenatal aneuploidy serum screening in a low-risk Hispanic Medicaid population in Massachusetts. STUDY DESIGN: We conducted a retrospective chart review of Spanish-speaking pregnant patients younger than 35 years of age who underwent aneuploidy serum screening at a Massachusetts community health center. The study compared the aneuploidy serum screening rates for the periods before and after May 2016 when the Massachusetts Medicaid program, MassHealth, temporarily discontinued reimbursement for the screening. Based on these rates, we developed a Markov cohort simulation model to assess the economic value of reimbursed aneuploidy screening vs nonreimbursed or limited screening. Clinical outcomes included trisomy 21, live births, and therapeutic abortions for a trisomy 21 diagnosis. Economic outcomes included discounted quality-adjusted life years and lifetime medical costs, net health benefit, and incremental cost-effectiveness ratios. RESULTS: Before the MassHealth policy change, 69% (55/80) of pregnant individuals selected quad or sequential screens in comparison with only 9% (10/112) who selected screens after the policy change. Traditional aneuploidy serum screening in a low-risk (aged <35 years) Hispanic population was considered to be cost-saving (ie, led to lower incremental costs and higher incremental benefits when compared with nonreimbursed or limited screening). CONCLUSION: From a United States healthcare payer perspective, aneuploidy serum screening for Hispanic pregnant individuals under 35 years of age is economically advantageous when compared with limited screening.

Buprenorphine Out-of-Pocket Costs and Discontinuation in Privately Insured Adults With Opioid Use Disorder.

This cohort study examined the association between out-of-pocket costs for an initial buprenorphine prescription and its discontinuation among commercially insured US adults with opioid use disorder.

Trends in the Use of Mifepristone for Medical Management of Early Pregnancy Loss From 2016 to 2020.

This study assesses the use of mifepristone plus misoprostol for miscarriage management among commercially insured adults in the US.

Maternal Opioid Use Disorder and the Risk of Postneonatal Infant Mortality.

Importance: The risk of serious long-term outcomes for infants born to individuals with opioid use disorder (OUD) is not fully characterized, nor is it well understood whether risks are modified by infant diagnosis of neonatal opioid withdrawal syndrome (NOWS). Objective: To characterize the risk of postneonatal infant mortality among infants with a NOWS diagnosis or born to individuals with OUD. Design, Setting, and Participants: The study team conducted a retrospective cohort study of 390 075 infants born from 2007 through 2018 to mothers who were enrolled in Tennessee Medicaid from 183 days prior to delivery through 28 days post partum (baseline). Maternal and infant baseline characteristics were measured using administrative claims and birth certificates, and infants were followed up from day 29 post partum through day 365 or death. Deaths were identified using linked death certificates through 2019. These data were analyzed from February 10, 2022, through March 3, 2023. Exposure: Infant exposures included birth to an individual with OUD or postnatal diagnosis of NOWS. The study team defined a pregnant individual's OUD status (maternal OUD) as having OUD diagnosis or a maintenance medication prescription fill during baseline; this study defined NOWS as having NOWS diagnosis up to day 28. Groups were categorized by exposures as maternal OUD with NOWS (OUD positive/NOWS positive), maternal OUD without NOWS (OUD positive/NOWS negative), no documented maternal OUD with NOWS (OUD negative/NOWS positive), and no documented maternal OUD or NOWS (OUD negative/NOWS negative, unexposed). Main Outcome and Measures: The outcome was postneonatal infant death, confirmed by death certificates. Cox proportional hazards models were used, adjusting for baseline maternal and infant characteristics, to estimate adjusted hazard ratios (aHRs) and 95% CIs for the association between maternal OUD or NOWS diagnosis with postneonatal death. Results: Pregnant individuals in the cohort had a mean (SD) age of 24.5 (5.2) years; 51% of infants were male. The study team observed 1317 postneonatal infant deaths and incidence rates of 3.47 (OUD negative/NOWS negative, 375 718), 8.41 (OUD positive/NOWS positive, 4922); 8.95 (OUD positive/NOWS negative, 7196), and 9.25 (OUD negative/NOWS positive, 2239) per 1000 person-years. After adjustment, the risk of postneonatal death was elevated for all groups, relative to the unexposed: OUD positive/NOWS positive (aHR, 1.54; 95% CI, 1.07-2.21), OUD positive/NOWS negative (aHR, 1.62; 95% CI, 1.21-2.17), and OUD negative/NOWS positive (aHR, 1.64; 95% CI, 1.02-2.65). Conclusions and Relevance: Infants born to individuals with OUD or with a NOWS diagnosis had an increased risk of postneonatal infant mortality. Future work is necessary to create and evaluate supportive interventions for individuals with OUD during and after pregnancy to reduce adverse outcomes.

County-level Factors and Treatment Access Among Insured Women With Opioid Use Disorder.

BACKGROUND: An over 40% increase in overdose deaths within the past 2 years and low levels of engagement in treatment call for a better understanding of factors that influence access to medication for opioid use disorder (OUD). OBJECTIVE: To examine whether county-level characteristics influence a caller's ability to secure an appointment with an OUD treatment practitioner, either a buprenorphine-waivered prescriber or an opioid treatment program (OTP). RESEARCH DESIGN AND SUBJECTS: We leveraged data from a randomized field experiment comprised of simulated pregnant and nonpregnant women of reproductive age seeking treatment for OUD among 10 states in the US. We employed a mixed-effects logistic regression model with random intercepts for counties to examine the relationship between appointments received and salient county-level factors related to OUD. MEASURES: Our primary outcome was the caller's ability to secure an appointment with an OUD treatment practitioner. County-level predictor variables included socioeconomic disadvantage rankings, rurality, and OUD treatment/practitioner density. RESULTS: Our sample comprised 3956 reproductive-aged callers; 86% reached a buprenorphine-waivered prescriber and 14% an OTP. We found that 1 additional OTP per 100,000 population was associated with an increase (OR=1.36, 95% CI: 1.08 to 1.71) in the likelihood that a nonpregnant caller receives an OUD treatment appointment from any practitioner. CONCLUSIONS: When OTPs are highly concentrated within a county, women of reproductive age with OUD have an easier time securing an appointment with any practitioner. This finding may suggest greater practitioners' comfort in prescribing when there are robust OUD specialty safety nets in the county.

Prevalence of Buprenorphine Providers Requiring Cash Payment From Insured Women Seeking Opioid Use Disorder Treatment.

CONTEXT: Medications for opioid use disorder (OUD) are known to be effective, especially in reducing the risk of overdose death. Yet, many individuals suffering from OUD are not receiving treatment. One potential barrier can be the patient's ability to access providers through their insurance plans. DATA AND METHODS: We used an audit (simulated patient) study methodology to examine appointment-granting behavior by buprenorphine prescribers in 10 different US states. Trained callers posed as women with OUD and were randomly assigned Medicaid or private insurance status. Callers request an OUD treatment appointment and then asked whether they would be able to use their insurance to cover the cost of care, or alternatively, whether they would be required to pay fully out-of-pocket. FINDINGS: We found that Medicaid and privately insured women were often asked to pay cash for OUD treatment--40% of the time over the full study sample. Such buprenorphine provider requests happened more than 60% of the time in some states. Areas with more providers or with more generous provider payments were not obviously more willing to accept the patient's insurance benefits for OUD treatment. Rural providers were less likely to require payment in cash in order for the woman to receive care. CONCLUSIONS: State-to-state variation was the most striking pattern in our field experiment data. The wide variation suggests that women of reproductive age with OUD in certain states face even greater challenges to treatment access than perhaps previously thought; however, it also reveals that some states have found ways to curtail this problem. Our findings encourage greater attention to this public health challenge and possibly opportunities for shared learning across states.

Family Spillover Effects: Are Economic Evaluations Misrepresenting the Value of Healthcare Interventions to Society?

The societal impacts of health interventions are seldom incorporated into health economic evaluations, including the impact that illness can have on informal or unpaid caregivers and other family members (i.e., "family spillover effects"). Previous research has demonstrated that by excluding family spillover effects, the value of health interventions may be underestimated on average. In this commentary, we discuss how the inclusion of spillover effects influences how we value interventions and, given the extent to which caregiver/family effects are largely not captured or known, propose ways in which these data could be more systematically collected or estimated and used by researchers. These recommendations include prioritizing data collection alongside clinical trials and patient registries, engaging expert opinion panels, and developing mapping algorithms for estimating caregiver/family utility values from non-preference-based caregiver health-related quality-of-life measures and/or from patient preference-based measures.

Supply-Side Cost-Effectiveness Thresholds: Questions for Evidence-Based Policy.

There is growing interest in cost-effectiveness thresholds as a tool to inform resource allocation decisions in health care. Studies from several countries have sought to estimate health system opportunity costs, which supply-side cost-effectiveness thresholds are intended to represent. In this paper, we consider the role of empirical estimates of supply-side thresholds in policy-making. Recent studies estimate the cost per unit of health based on average displacement or outcome elasticity. We distinguish the types of point estimates reported in empirical work, including marginal productivity, average displacement, and outcome elasticity. Using this classification, we summarise the limitations of current approaches to threshold estimation in terms of theory, methods, and data. We highlight the questions that arise from alternative interpretations of thresholds and provide recommendations to policymakers seeking to use a supply-side threshold where the evidence base is emerging or incomplete. We recommend that: (1) policymakers must clearly define the scope of the application of a threshold, and the theoretical basis for empirical estimates should be consistent with that scope; (2) a process for the assessment of new evidence and for determining changes in the threshold to be applied in policy-making should be created; (3) decision-making processes should retain flexibility in the application of a threshold; and (4) policymakers should provide support for decision-makers relating to the use of thresholds and the implementation of decisions stemming from their application.

Cost-Effectiveness of Operating on Traumatic Spinal Injuries in Low-Middle Income Countries: A Preliminary Report From a Major East African Referral Center.

STUDY DESIGN: Retrospective cost-effectiveness analysis. OBJECTIVES: While the incidence of traumatic spine injury (TSI) is high in low-middle income countries (LMICs), surgery is rarely possible due to cost-prohibitive implants. The objective of this study was to conduct a preliminary cost-effectiveness analysis of operative treatment of TSI patients in a LMIC setting. METHODS: At a tertiary hospital in Tanzania from September 2016 to May 2019, a retrospective analysis was conducted to estimate the cost-effectiveness of operative versus nonoperative treatment of TSI. Operative treatment included decompression/stabilization. Nonoperative treatment meant 3 months of bed rest. Direct costs included imaging, operating fees, surgical implants, and length of stay. Four patient scenarios were chosen to represent the heterogeneity of spine trauma: Quadriplegic, paraplegic, neurologic improvement, and neurologically intact. Disability-adjusted-life-years (DALYs) and incremental-cost-effectiveness ratios were calculated to determine the cost per unit benefit of operative versus nonoperative treatment. Cost/DALY averted was the primary outcome (i.e., the amount of money required to avoid losing 1 year of healthy life). RESULTS: A total of 270 TSI patients were included (125 operative; 145 nonoperative). Operative treatment averaged $731/patient. Nonoperative care averaged $212/patient. Comparing operative versus nonoperative treatment, the incremental cost/DALY averted for each patient outcome was: quadriplegic ($112-$158/DALY averted), paraplegic ($47-$67/DALY averted), neurologic improvement ($50-$71/DALY averted), neurologically intact ($41-$58/DALY averted). Sensitivity analysis confirmed these findings without major differences. CONCLUSIONS: This preliminary cost-effectiveness analysis suggests that the upfront costs of spine trauma surgery may be offset by a reduction in disability. LMIC governments should consider conducting more spine trauma cost-effectiveness analyses and including spine trauma surgery in universal health care.

Medicaid prevalence and opioid use disorder treatment access disparities.

OBJECTIVE: To examine how variation in the size of the local Medicaid population moderates Medicaid-to-private treatment access differentials for women with opioid use disorder (OUD). DATA SOURCES: County-level information on total Medicaid enrollment combined with randomized field experiment data from 10 diverse states that used a simulated patient (audit) methodology to examine buprenorphine providers' appointment granting behavior. STUDY DESIGN: We used multiple regression modeling approaches to capture the moderating influence of Medicaid prevalence on differences in the likelihood of receiving an insurance-covered appointment between Medicaid and privately insured female patients. DATA EXTRACTION: Completed calls to buprenorphine treatment providers. PRINCIPAL FINDINGS: We find a 0.37 percentage point (p value <0.01) narrowing of the Medicaid-to-private access gap with each one percentage point increase in the local insured population on Medicaid. There is effectively no difference in the likelihood of being granted an insurance-covered appointment across the two payer groups in the top tercile of Medicaid penetration. CONCLUSIONS: When Medicaid is a common source of insurance within the local population, buprenorphine providers are much less likely to discriminate between Medicaid and privately insured prospective patients. Efforts to enhance equitable access across patient groups are perhaps best targeted where Medicaid prevalence is lower.

Modelling the potential cost-effectiveness of food-based programs to reduce malnutrition.

Poor quality diets contribute to malnutrition globally, but evidence is weak on the cost-effectiveness of food-based interventions that shift diets. This study assessed 11 candidate interventions developed through Delphi techniques to improve diets in India, Nigeria, and Ethiopia. A Markov simulation model incorporated time, individual-level, nutrition, and policy parameters to estimate health impacts and cost-effectiveness for reducing stunting, anaemia, diarrhea, and mortality in preschool children. At an assumed 80% coverage, interventions considered would potentially save between 0·16 and 3·20 years of life per child. The average cost-effectiveness ratio ranged from US$9 to US$2000 per life year saved. This approach, linking expert knowledge, known costs, and modelling, offers potential for estimating cost-effective investments for better informed policy choice where empirical evidence is limited.

Cost-Effectiveness of First-Line Tyrosine Kinase Inhibitor Therapy Initiation Strategies for Chronic Myeloid Leukemia.

OBJECTIVES: Overall survival in chronic myeloid leukemia (CML) in chronic phase is not significantly different by treatment with first-line tyrosine kinase inhibitors (TKIs), but emerging evidence reveals differences in costs and safety profiles. We evaluated the 1-year cost-effectiveness of TKI initiation with imatinib, dasatinib, or nilotinib among a hypothetical cohort of incident patients with CML from a US payer's perspective. METHODS: We constructed a decision analytic model to assess quality-adjusted life years (QALYs), healthcare costs, net monetary benefit, and incremental cost-effectiveness of treatment strategies. We used published studies and data from the IBM Watson Health MarketScan database for model parameters. To calculate TKI costs, we used the 2018 Federal Supply Schedule estimates for generic imatinib and branded second-generation TKIs. We evaluated cost-effectiveness under various willingness-to-pay thresholds. We accounted for uncertainty with deterministic and probabilistic sensitivity analyses. RESULTS: In the base-case analysis, imatinib was favored over dasatinib and nilotinib at a lower cost per QALY gained. Imatinib remained the favored strategy after 1-way variations in TKI costs, TKI switching, QALYs, adverse event risk, and CML progression. When we assessed model uncertainty with prespecified parameter distributions, imatinib was cost-saving compared with dasatinib in 40% of 100 0000 simulations and was favored over all simulations compared with nilotinib. First-line treatment with second-generation TKIs was cost-effective in 50% of simulations at a $200 000/QALY willingness-to-pay threshold. CONCLUSIONS: Generic availability of imatinib provides a more cost-effective treatment approach in the first year compared with other available TKIs for newly diagnosed patients with CML.