Patient preferences and health state utilities associated with the treatment process of antiretroviral therapy for people living with HIV.

PURPOSE: People living with HIV (PLHIV) have reported challenges associated with daily oral antiretroviral therapy (ART), including missed doses, negative psychological impact, and difficulty remaining discreet while at home or traveling. Recently approved long-acting injectable (LAI) ART may help eliminate these concerns. The purpose of this study was to examine patient preferences and estimate health state utilities associated with oral and LAI treatment for ART. METHODS: Four health state vignettes were developed based on published literature, clinician interviews, and a pilot study. All vignettes included the same description of HIV, but differed in treatment regimens: (A) single daily oral tablet, (B) two daily oral tablets, (C) injections once monthly, and (D) injections every two months. PLHIV in the UK reported their preferences and valued the health states in time trade-off utility interviews. RESULTS: The sample included 201 PLHIV (83.1% male; mean age = 44.9y). The health states frequently selected as most preferable were D (n = 119; 59.2%) and A (n = 75; 37.3%). Utility differences among health states were relatively small, which is typical for treatment process utilities (mean utilities: A, 0.908; B, 0.905; C, 0.900; D, 0.910). Statistically significant differences in utility were found for one vs. two tablets and injections every month vs. every two months (p < 0.001). Participants' quotations highlight the wide range of reasons for treatment process preferences. CONCLUSIONS: Current results indicate that many PLHIV would prefer LAI ART. The reported utilities may be useful in economic modeling comparing oral vs. LAI ART.

Indirect comparison of 48-week efficacy and safety of long-acting cabotegravir and rilpivirine maintenance every 8 weeks with daily oral standard of care antiretroviral therapy in participants with virologically suppressed HIV-1-infection.

BACKGROUND: Efficacy and safety of long-acting cabotegravir (CAB) + rilpivirine (RPV) every 8 weeks (Q8W) versus daily oral standard of care (SoC) maintenance in treatment-experienced individuals with virologically suppressed human immunodeficiency virus type 1 (HIV-1) has not been directly compared in randomized clinical trials. This analysis aimed to indirectly compare these regimens. METHODS: An adjusted indirect treatment comparison of CAB + RPV Q8W with daily oral SoC was performed, using Phase 3 data from studies of CAB + RPV every 4 weeks (Q4W) vs SoC (ATLAS/FLAIR, n = 591 per group) and a Phase 3b trial of CAB + RPV Q8W vs Q4W (ATLAS-2M [excluding participants with prior CAB + RPV exposure]; n = 327 per group). Eligible participants were virologically suppressed (viral load < 50 HIV-1 ribonucleic acid (RNA) copies/mL), treatment-experienced individuals with HIV-1-infection. Treatment efficacy and safety assessments at Week 48 included virologic suppression and lack of virologic suppression (proportion of participants with plasma HIV-1 RNA < 50 copies/mL or ≥ 50 copies/mL, respectively; both as per FDA snapshot algorithm), CD4-cell count change from baseline, no virologic data, discontinuations due to adverse events (AEs), and overall AEs, serious AEs and Grade 3-5 AEs excluding injection-site reactions. A subgroup analysis stratified by baseline third active drug class was performed. RESULTS: Baseline characteristics between the Q4W arms of ATLAS/FLAIR and ATLAS-2M showed no significant differences or differences were not judged to be clinically relevant, apart from participants switching from a baseline third active drug class; more participants switched from integrase strand inhibitors in ATLAS/FLAIR, and from non-nucleoside reverse transcriptase inhibitors in ATLAS-2M. Injections of CAB + RPV Q8W showed no significant differences across efficacy and safety outcomes versus daily oral SoC. Univariate subgroup analysis found there were no significant differences on virologic suppression or lack of virologic suppression for any baseline third active drug class subgroup. These results suggest that CAB + RPV Q8W is non-inferior to daily oral SoC. CONCLUSIONS: This analysis supports the therapeutic potential of CAB + RPV Q8W for virologically suppressed people living with HIV-1 infection seeking an alternative maintenance treatment option to daily oral SoC. TRIAL REGISTRATION: NCT02938520, NCT02951052, NCT03299049.

Factors associated with interest in a long-acting HIV regimen: perspectives of people living with HIV and healthcare providers in four European countries.

OBJECTIVES: A novel long-acting regimen (LAR) of cabotegravir and rilpivirine for HIV treatment requires dosing every 2 months instead of daily. We assessed what proportion of people living with HIV and physicians would be interested in trying and offering LAR respectively and why. METHODS: 688 people living with HIV on treatment, and 120 HIV physicians completed web-based surveys in Germany, Italy, the UK and France during 2019. Balanced description of a hypothetical LAR regarding efficacy, administration and possible side effects were provided. The hypothetical long-acting injections were assumed to be cost-neutral to current daily oral antiretrovirals. Interest of people living with HIV in trying ('very'/'highly') and physicians' willingness to offer ('definitely'/'probably') this LAR in different situations, with perceived benefits/concerns was measured. RESULTS: Of people living with HIV, 65.8% were interested in trying LAR. The majority (~80%-90%) of those with unmet needs felt LAR would help, including those with strong medical needs (malabsorption and interfering gastrointestinal conditions), suboptimal adherence, confidentiality/privacy concerns and emotional burden of daily dosing. Of physicians, percentage willing to offer LAR varied situationally: strong medical need (dysphagia, 93.3%; malabsorption, 91.6%; interfering gastrointestinal issues, 90.0%; central nervous system disorders, 87.5%); suboptimal adherence (84.2%); confidentiality/privacy concerns (hiding medications, 86.6%) and convenience/lifestyle (84.2%). People living with HIV liked LAR for not having to carry pills when travelling (56.3%); physicians liked the increased patient contact (54.2%). Furthermore, 50.0% of people living with HIV perceived LAR would minimise transmission risk and improve their sexual health. The most disliked attribute was scheduling appointments (37.2%) and resource constraints (57.5%) for people living with HIV and physicians, respectively. Physicians estimated 25.7% of their patients would actually switch. CONCLUSION: Providers and people living with HIV viewed the described LAR as addressing several unmet needs. Alternative treatment routes and especially LAR may improve adherence and quality of life.

Undetectable equals untransmittable (U = U): awareness and associations with health outcomes among people living with HIV in 25 countries.

OBJECTIVES: 'Undetectable equals Untransmittable' (U=U) is an empowering message that may enable people living with HIV (PLHIV) to reach and maintain undetectability. We estimated the percentage of PLHIV who ever discussed U=U with their main HIV care provider, and measured associations with health-related outcomes. Secondarily, we evaluated whether the impact of the U=U message varied between those who heard it from their healthcare provider (HCP) vs from elsewhere. METHODS: Data were from the 25-country 2019 Positive Perspectives Survey of PLHIV on treatment (n=2389). PLHIV were classified as having discussed U=U with their HCP if they indicated that their HCP had ever told them about U=U. Those who had not discussed U=U with their HCP but were nonetheless aware that 'My HIV medication prevents me from passing on HIV to others' were classified as being made aware of U=U from non-HCP sources. Multivariable logistic regression was used to measure associations between exposure to U=U messages and health outcomes. RESULTS: Overall, 66.5% reported ever discussing U=U with their HCP, from 38.0% (South Korea) to 87.3% (Switzerland). Prevalence was lowest among heterosexual men (57.6%) and PLHIV in Asia (51.3%). Compared with those unaware of U=U, those reporting U=U discussions with their HCP had lower odds of suboptimal adherence (AOR=0.59, 95% CI 0.44 to 0.78) and higher odds of self-reported viral suppression (AOR=2.34, 95% CI 1.72 to 3.20), optimal sexual health (AOR=1.48, 95% CI 1.14 to 1.92) and reporting they 'always shared' their HIV status (AOR=2.99, 95% CI 1.42 to 6.28). While exposure to U=U information from non-HCP sources was beneficial too, the observed associations were attenuated relative to those seen with reported discussions with HCPs. CONCLUSION: HCP discussion of U=U with PLHIV was associated with favourable health outcomes. However, missed opportunities exist since a third of PLHIV reported not having any U=U discussion with their HCP. U=U discussions with PLHIV should be considered as a standard of care in clinical guidelines.

Regional differences in perceived treatments needs and priorities in relation to antiretroviral therapy among people living with HIV in 25 countries.

While geographic differences in HIV burden are well documented, less is known about regional differences in perceived treatment needs. To fill this gap, the 2019 Positive Perspectives study of people living with HIV (PLHIV) was conducted in 25 countries across Northern America, Latin America, the Asian region, Europe (EU/Schengen countries), Russia, Australia, and South Africa (n = 2389). Overall mean duration of HIV was 10.1 (SD = 9.6) years. The perception that HIV had a negative impact on day-to-day life was lowest among participants from South Africa (14.0%[25/179]) and highest among participants from the Asian region (55.2%[127/230]). Most of the regional gap in the perception that HIV had a negative impact on daily life was explained by regional differences in medication-related unmet needs, stigma, demographic factors, and comorbidities. The percentage who felt they understood their treatment was highest among participants from Australia (87.5%[105/120]) and lowest among those from Russia (62.0%[93/150]), the Asian region (62.2%[143/230]), and South Africa (62.6%[112/179]). Among participants from Northern America, Europe, and Latin America, the treatment goals with the largest absolute increase in perceived importance, from time of starting treatment to time of survey among those diagnosed for ≥1 year, were minimizing the long term impact of antiretroviral treatment and keeping the number of medicines in their antiretroviral regimen at a minimum. Tailored approaches to care of PLHIV are needed as different regions have different disease burden and treatment needs. Equitable approaches to HIV care are needed across and within regions to ensure that patients' unmet needs and preferences are addressed to improve their overall wellbeing and health-related quality of life.

Physical, Emotional, and Psychosocial Challenges Associated with Daily Dosing of HIV Medications and Their Impact on Indicators of Quality of Life: Findings from the Positive Perspectives Study.

To assess challenges with daily oral antiretroviral therapy (ART), we analyzed data for 2389 participants in the 2019 Positive Perspectives survey of people living with HIV in 25 countries. ART-related challenges reported included difficulty swallowing pills (33.1% [790/2389]); stress from daily dosing routine (33.3% [795/2389]); bad memories from daily intake of HIV medication (35.1%[839/2389]), and concern "that having to take pills every day means a greater chance of revealing my HIV status to others" (37.9% [906/2389]). Individuals who felt empowered by daily oral dosing ["taking my pill(s) every day reassures me that my HIV is being kept under control"] had 69% higher odds of optimal overall health (AOR 1.69, 95% CI 1.40-2.04). Conversely, odds of optimal overall health were lower among those who felt daily pill intake "limits my day-to-day life" (AOR 0.53, 95% CI 0.44-0.64). These findings show that there is need for increased flexibility of ART delivery to meet diverse patient needs.

Shared Decision Making Between Patients and Healthcare Providers and its Association with Favorable Health Outcomes Among People Living with HIV.

We assessed patient-provider communication in HIV care; data were from the 2019 Positive Perspectives Survey of people living with HIV (PLHIV) from 25 countries (n = 2389). A significantly greater proportion of recently diagnosed individuals were interested in being involved when it comes to decisions about their HIV treatment compared with any other group (72.8% [399/548], 63.1% [576/913], and 62.6% [581/928], diagnosis year: 2017-2019, 2010-2016, and pre-2010 respectively) but reported less understanding of their treatment compared with those reporting the longest duration (66.8% [366/548], 68.6% [626/913], and 77.3% [717/928], respectively). One-third of PLHIV with salient treatment-related concerns were uncomfortable discussing with providers. Of participants who felt that their HIV medication limited their life but did not discuss their concerns with their provider (n = 203), top reasons for not discussing were: perception nothing could be done (49.3% [100/203]), provider never brought up the issue (37.9% [77/203]), and not wanting to appear difficult (30.5% [62/203]). To continue to identify and address unmet treatment needs among PLHIV, providers need to ensure that there is ongoing open dialogue.

Dose-related and contextual aspects of suboptimal adherence to antiretroviral therapy among persons living with HIV in Western Europe.

BACKGROUND: The daily oral dosing requirement for antiretroviral therapy (ART) may be challenging for some people living with HIV (PLWHIV) with comorbid conditions, confidentiality concerns or pill fatigue. We investigated suboptimal adherence from the perspective of PLWHIV and HIV physicians. METHODS: PLWHIV on ART (n = 688) and HIV physicians (n = 120) were surveyed during 2019 in France, Germany, Italy and the UK. Suboptimal adherence was a report the participant missed taking their dose as prescribed 'Sometimes'/'Often'/'Very often'. Physicians' interest in offering a hypothetical long-acting HIV regimen for suboptimally adherent patients was assessed. Descriptive and multivariable analyses were performed (P < 0.05). RESULTS: Of PLWHIV, 23.8% (164/688) reported suboptimal adherence vs. providers' estimated prevalence of 33.6% (SD = 28.8). PLWHIV-reported prevalence of specific suboptimal adherence behaviors were: mistimed dose [16.1% (111/688)]; missed a dose [15.7% (108/688)]; dosed under wrong conditions [e.g. food restrictions, 10.5% (72/688)] and overdosed [3.3% (23/688)]. Odds of suboptimal adherence were higher among those with vs. without a report of the following: dysphagia (AOR = 3.61, 95% CI = 2.28-5.74), stress/anxiety because of their daily dosing schedule (AOR = 3.09, 95% CI = 1.97-4.85), gastrointestinal side effects (AOR = 2.09, 95% CI = 1.39-3.15), neurocognitive/mental health conditions (AOR = 1.88, 95% CI = 1.30-2.72) or hiding their HIV medication (AOR = 1.51, 95% CI = 1.04-2.19). Of providers, 84.2% indicated they Definitely/Probably will offer a hypothetical long-acting HIV regimen 'for patients who have suboptimal levels of adherence to daily oral therapy (50-90%) for non-medical reasons'. CONCLUSIONS: Dysphagia, stressful daily oral dosing schedule, gastrointestinal side effects, neurocognitive/mental health conditions and confidentiality concerns were associated with suboptimal adherence in our study. Adherence support and alternative regimens, such as long-acting antiretroviral therapies, could help address these challenges.

Prevalence, determinants, and impact of suboptimal adherence to HIV medication in 25 countries.

Modern antiretroviral therapy (ART) has improved the lives of people living with HIV (PLHIV) but currently requires daily adherence. We assessed prevalence and correlates of suboptimal adherence, and measured associations with self-reported health outcomes. Data were from web-based surveys of confirmed HIV+ adults on antiretroviral treatment within 25 countries during 2019 (n = 2389). Suboptimal adherence was a report of ≥1 reason for missing ART ≥5 times within the past month. Multivariable logistic regression examined associations between suboptimal adherence and self-reported overall health and virologic suppression. Overall, 24.1% (575/2389) reported suboptimal adherence, from 10.0% (5/50) in Austria, to 62.0% (31/50) in China. The most common reasons for missing ART ≥5 times in the overall population were feeling depressed/overwhelmed (7.4%, 176/2389), trying to forget about HIV (7.0%, 168/2389), and work (6.1%, 145/2389). Correlates of suboptimal adherence included being heterosexual, <50 years old, ≤high school, having gastrointestinal treatment side effects, and privacy concerns. Odds of suboptimal overall health were 1.41 (95%CI, 1.11-1.80), 2.10 (95%CI, 1.65-2.68), and 2.55 (95%CI, 2.00-3.25) among those who reported the maximum number of times missed ART for any reason within the past month as 1, 2-4, or ≥5 times respectively, vs not missing at all. Odds of virologic nonsuppression were 1.80 (95%CI, 1.33-2.45), and 2.24 (95%CI, 1.66-3.02) for 2-4, or ≥5 times of missed ART respectively, vs not missing at all; missing for only 1 time was not significantly associated with virologic nonsuppression. Novel ART strategies designed to improve adherence along with interventions to empower PLHIV and support self-medication may improve health outcomes and quality of life.

A DELPHI study on aspects of study design to overcome knowledge gaps on the burden of disease caused by serogroup B invasive meningococcal disease.

BACKGROUND: Value assessment of vaccination programs against serogroup B invasive meningococcal disease (IMD) is on the agenda of public health authorities. Current evidence on the burden due to IMD is unfit for pinning down the nature and magnitude of the full social and economic costs of IMD for two reasons. First, the concepts and components that need to be studied are not agreed, and second, measures of the concepts that have been studied are weak and inconsistent. Thus, the economic evaluation of the available serogroup B meningococcal (MenB) vaccines is difficult. The aims of this DELPHI study are to: (1) agree on the concepts and components determining the burden of MenB diseases that need to be studied; and (2) seek consensus on appropriate methods and study designs to measure quality of life (QoL) associated with MenB induced long-term sequelae in future studies. METHODS: We designed a DELPHI questionnaire based on the findings of a recent systematic review on the QoL associated with IMD-induced long-term sequelae, and iteratively interviewed a panel of international experts, including physicians, health economists, and patient representatives. Experts were provided with a controlled feedback based on the results of the previous round. RESULTS: Experts reached consensus on all questions after two DELPHI rounds. Major gaps in the literature relate (i) to the classification of sequelae, which allows differentiation of severity levels, (ii) to the choice of QoL measures, and (iii) to appropriate data sources to examine long-term changes and deficits in patients' QoL. CONCLUSIONS: Better conceptualisation of the structure of IMD-specific sequelae and of how their diverse forms of severity might impact the QoL of survivors of IMD as well as their family network and care-providers is needed to generate relevant, reliable and generalisable data on QoL in the future. The results of this DELPHI panel provide useful guidance on how to choose the study design, target population and appropriate QoL measures for future research and hence, help promote the appropriateness and consistency in study methodology and sample characteristics.

Public health impact and cost-effectiveness of the RTS,S/AS01 malaria vaccine: a systematic comparison of predictions from four mathematical models.

BACKGROUND: The phase 3 trial of the RTS,S/AS01 malaria vaccine candidate showed modest efficacy of the vaccine against Plasmodium falciparum malaria, but was not powered to assess mortality endpoints. Impact projections and cost-effectiveness estimates for longer timeframes than the trial follow-up and across a range of settings are needed to inform policy recommendations. We aimed to assess the public health impact and cost-effectiveness of routine use of the RTS,S/AS01 vaccine in African settings. METHODS: We compared four malaria transmission models and their predictions to assess vaccine cost-effectiveness and impact. We used trial data for follow-up of 32 months or longer to parameterise vaccine protection in the group aged 5-17 months. Estimates of cases, deaths, and disability-adjusted life-years (DALYs) averted were calculated over a 15 year time horizon for a range of levels of Plasmodium falciparum parasite prevalence in 2-10 year olds (PfPR2-10; range 3-65%). We considered two vaccine schedules: three doses at ages 6, 7·5, and 9 months (three-dose schedule, 90% coverage) and including a fourth dose at age 27 months (four-dose schedule, 72% coverage). We estimated cost-effectiveness in the presence of existing malaria interventions for vaccine prices of US$2-10 per dose. FINDINGS: In regions with a PfPR2-10 of 10-65%, RTS,S/AS01 is predicted to avert a median of 93,940 (range 20,490-126,540) clinical cases and 394 (127-708) deaths for the three-dose schedule, or 116,480 (31,450-160,410) clinical cases and 484 (189-859) deaths for the four-dose schedule, per 100,000 fully vaccinated children. A positive impact is also predicted at a PfPR2-10 of 5-10%, but there is little impact at a prevalence of lower than 3%. At $5 per dose and a PfPR2-10 of 10-65%, we estimated a median incremental cost-effectiveness ratio compared with current interventions of $30 (range 18-211) per clinical case averted and $80 (44-279) per DALY averted for the three-dose schedule, and of $25 (16-222) and $87 (48-244), respectively, for the four-dose schedule. Higher ICERs were estimated at low PfPR2-10 levels. INTERPRETATION: We predict a significant public health impact and high cost-effectiveness of the RTS,S/AS01 vaccine across a wide range of settings. Decisions about implementation will need to consider levels of malaria burden, the cost-effectiveness and coverage of other malaria interventions, health priorities, financing, and the capacity of the health system to deliver the vaccine. FUNDING: PATH Malaria Vaccine Initiative; Bill & Melinda Gates Foundation; Global Good Fund; Medical Research Council; UK Department for International Development; GAVI, the Vaccine Alliance; WHO.

Potential public health impact of RTS,S malaria candidate vaccine in sub-Saharan Africa: a modelling study.

BACKGROUND: Adding malaria vaccination to existing interventions could help to reduce the health burden due to malaria. This study modelled the potential public health impact of the RTS,S candidate malaria vaccine in 42 malaria-endemic countries in sub-Saharan Africa. METHODS: An individual-based Markov cohort model was constructed with three categories of malaria transmission intensity and six successive malaria immunity levels. The cycle time was 5 days. Vaccination was assumed to reduce the risk of infection, with no other effects. Vaccine efficacy was assumed to wane exponentially over time. Malaria incidence and vaccine efficacy data were taken from a Phase III trial of the RTS,S vaccine with 18 months of follow-up (NCT00866619). The model was calibrated to reproduce the malaria incidence in the control arm of the trial in each transmission category and published age distribution data. Individual-level heterogeneity in malaria exposure and vaccine protection was accounted for. Parameter uncertainty and variability were captured by using stochastic model transitions. The model followed a cohort from birth to 10 years of age without malaria vaccination, or with RTS,S malaria vaccination administered at age 6, 10 and 14 weeks or at age 6, 7-and-a-half and 9 months. Median and 95% confidence intervals were calculated for the number of clinical malaria cases, severe cases, malaria hospitalizations and malaria deaths expected to be averted by each vaccination strategy. Univariate sensitivity analysis was conducted by varying the values of key input parameters. RESULTS: Vaccination assuming the coverage of diphtheria-tetanus-pertussis (DTP3) at age 6, 10 and 14 weeks is estimated to avert over five million clinical malaria cases, 119,000 severe malaria cases, 98,600 malaria hospitalizations and 31,000 malaria deaths in the 42 countries over the 10-year period. Vaccination at age 6, 7-and-a-half and 9 months with 75% of DTP3 coverage is estimated to avert almost 12.5 million clinical malaria cases, 250,000 severe malaria cases, 208,000 malaria hospitalizations and 65,400 malaria deaths in the 42 countries. Univariate sensitivity analysis indicated that for both vaccination strategies, the parameters with the largest impact on the malaria mortality estimates were waning of vaccine efficacy and malaria case-fatality rate. CONCLUSIONS: Addition of RTS,S malaria vaccination to existing malaria interventions is estimated to reduce substantially the incidence of clinical malaria, severe malaria, malaria hospitalizations and malaria deaths across 42 countries in sub-Saharan Africa.

Reply to Volkman et al. Comment on "Fust et al. The Potential Economic Impact of the Updated COVID-19 mRNA Fall 2023 Vaccines in Japan. Vaccines 2024, 12, 434".

In their comment [...].

Real-World Effectiveness of a Third Dose of mRNA-1273 Versus BNT162b2 on Inpatient and Medically Attended COVID-19 Among Immunocompromised US Adults.

INTRODUCTION: Recent data have shown elevated infection rates in several subpopulations at risk of SARS-CoV-2 infection and COVID-19, including immunocompromised (IC) individuals. Previous research suggests that IC persons have reduced risks of hospitalization and medically attended COVID-19 with two doses of mRNA-1273 (SpikeVax; Moderna) compared to two doses of BNT162b2 (Comirnaty; Pfizer/BioNTech). The main objective of this retrospective cohort study was to compare real-world effectiveness of third doses of mRNA-1273 versus BNT162b2 at multiple time points on occurrence of COVID-19 hospitalization and medically attended COVID-19 among IC adults in the United States (US). METHODS: This retrospective, observational comparative effectiveness study identified patients from the US HealthVerity database from December 11, 2020, through August 31, 2022. Medically attended SARS-CoV-2 infections and hospitalizations were assessed following a three-dose mRNA-1273 versus BNT162b2 regimen. Inverse probability weighting was applied to balance baseline confounders between vaccine groups. Relative risk (RR) and risk difference were calculated for subgroup and sensitivity analyses using a non-parametric method. RESULTS: In propensity score-adjusted analyses, receiving mRNA-1273 vs. BNT162b2 as third dose was associated with 32.4% (relative risk 0.676; 95% confidence interval 0.506-0.887), 29.3% (0.707; 0.573-0.858), and 23.4% (0.766; 0.626-0.927) lower risk of COVID-19 hospitalization after 90, 180, and 270 days, respectively. Corresponding reductions in medically attended COVID-19 were 8.4% (0.916; 0.860-0.976), 6.4% (0.936; 0.895-0.978), and 2.4% (0.976; 0.935-1.017), respectively. CONCLUSIONS: Our findings suggest a third dose of mRNA-1273 is more effective than a third dose of BNT162b2 in preventing COVID-19 hospitalization and breakthrough medically attended COVID-19 among IC adults in the US.

Vaccine preparation time, errors, satisfaction, and preference of prefilled syringes versus RSV vaccines requiring reconstitution: randomized, time and motion study.

AIM: The current study compared preparation time, errors, satisfaction, and preference for a prefilled syringe (PFS) versus two RSV vaccines requiring reconstitution (VRR1 and VRR2) in a randomized, single-blinded time and motion study. METHODS: Pharmacists, nurses, and pharmacy technicians were randomized to a preparation sequence of the three vaccines. Participants read instructions, then consecutively prepared the three vaccines with a 3-5-min washout period in between. Preparations were video recorded and reviewed by a trained pharmacist for preparation time and errors using predefined, vaccine-specific checklists. Participant demographics, satisfaction with vaccine preparation, and vaccine preference were recorded. Within-subjects analysis of variance was used to compare preparation time. Mixed-effects Poisson and ordered logistic regression models were used to compare the number of preparation errors and satisfaction scores, respectively. RESULTS: Sixty-three pharmacists (60%), nurses (35%), and pharmacy technicians (5%) participated at four sites in the United States. The least squares mean preparation time per dose for PFS was 141.8 s (95% CI = 156.8-126.7; p <.0001) faster than for VRR1, 103.6 s (95% CI = 118.7-88.5; p <.0001) faster than for VRR2, and 122.7 s (95% CI = 134.2-111.2; p <.0001) faster than the pooled VRRs. Overall satisfaction (combined "Very" and "Extremely") was 87.3% for PFS, 28.6% for VRR1, and 47.6% for VRR2. Most participants (81.0%) preferred the PFS vaccine. LIMITATIONS: The study is limited by the inability to completely blind observers. To minimize the effects of order, we utilized a 3-sequence block design; however, the order in which the vaccines were prepared may have affected outcomes. Participants were assessed once, whereas if repeated preparations were performed there may have been trained efficiencies gained for each vaccine. CONCLUSION: PFS vaccines can greatly simplify the vaccine preparation process, allowing administrators to prepare almost four times more doses per hour than with vial and syringe systems.

Clinical impact and cost-effectiveness of the updated COVID-19 mRNA Autumn 2023 vaccines in Germany.

OBJECTIVES: To assess the potential clinical impact and cost-effectiveness of coronavirus disease 2019 (COVID-19) mRNA vaccines updated for Autumn 2023 in adults aged ≥60 years and high-risk persons aged 30-59 years in Germany over a 1-year analytic time horizon (September 2023-August 2024). METHODS: A compartmental Susceptible-Exposed-Infected-Recovered model was updated and adapted to the German market. Numbers of symptomatic infections, a number of COVID-19 related hospitalizations and deaths, costs, and quality-adjusted life-years (QALYs) gained were calculated using a decision tree model. The incremental cost-effectiveness ratio of an Autumn 2023 Moderna updated COVID-19 (mRNA-1273.815) vaccine was compared to no additional vaccination. Potential differences between the mRNA-1273.815 and the Autumn Pfizer-BioNTech updated COVID-19 (XBB.1.5 BNT162b2) vaccines, as well as societal return on investment for the mRNA-1273.815 vaccine relative to no vaccination, were also examined. RESULTS: Compared to no autumn vaccination, the mRNA-1273.815 campaign is predicted to prevent approximately 1,697,900 symptomatic infections, 85,400 hospitalizations, and 4,100 deaths. Compared to an XBB.1.5 BNT162b2 campaign, the mRNA-1273.815 campaign is also predicted to prevent approximately 90,100 symptomatic infections, 3,500 hospitalizations, and 160 deaths. Across both analyses we found the mRNA-1273.815 campaign to be dominant. CONCLUSIONS: The mRNA-1273.815 vaccine can be considered cost-effective relative to the XBB.1.5 BNT162b2 vaccine and highly likely to provide more benefits and save costs compared to no vaccine in Germany, and to offer high societal return on investment.

The Potential Economic Impact of the Updated COVID-19 mRNA Fall 2023 Vaccines in Japan.

This analysis estimates the economic and clinical impact of a Moderna updated COVID-19 mRNA Fall 2023 vaccine for adults ≥18 years in Japan. A previously developed Susceptible-Exposed-Infected-Recovered (SEIR) model with a one-year analytic time horizon (September 2023-August 2024) and consequences decision tree were used to estimate symptomatic infections, COVID-19 related hospitalizations, deaths, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER) for a Moderna updated Fall 2023 vaccine versus no additional vaccination, and versus a Pfizer-BioNTech updated mRNA Fall 2023 vaccine. The Moderna vaccine is predicted to prevent 7.2 million symptomatic infections, 272,100 hospitalizations and 25,600 COVID-19 related deaths versus no vaccine. In the base case (healthcare perspective), the ICER was ¥1,300,000/QALY gained ($9400 USD/QALY gained). Sensitivity analyses suggest results are most affected by COVID-19 incidence, initial vaccine effectiveness (VE), and VE waning against infection. Assuming the relative VE between both bivalent vaccines apply to updated Fall 2023 vaccines, the base case suggests the Moderna version will prevent an additional 1,100,000 symptomatic infections, 27,100 hospitalizations, and 2600 deaths compared to the Pfizer-BioNTech vaccine. The updated Moderna vaccine is expected to be highly cost-effective at a ¥5 million willingness-to-pay threshold across a wide range of scenarios.

Real-world comparative effectiveness of a third dose of mRNA-1273 versus BNT162b2 among adults aged ≥ 65 years in the United States.

INTRODUCTION: To compare the real-world effectiveness of a third dose of mRNA-1273 versus a third dose of BNT162b2 against breakthrough COVID-19 hospitalizations among adults aged ≥ 65 years who completed a primary series of an mRNA-based COVID-19 vaccine (regardless of which primary series was received). MATERIALS AND METHODS: This observational comparative vaccine effectiveness (VE) study was conducted using administrative claims data from the US HealthVerity database (September 22, 2021, to August 31, 2022). A third dose of mRNA-1273 versus BNT162b2 was assessed for preventing COVID-19 hospitalizations and medically attended COVID-19 among adults aged ≥ 65 years. Inverse probability of treatment weighting was applied to balance baseline characteristics between vaccine groups. Incidence rates from patient-level data and hazard ratios (HRs) with 95 % confidence intervals (CIs) using weighted Cox proportional hazards models were calculated to estimate relative VE for each outcome. RESULTS: Overall, 94,587 and 92,377 individuals received a third dose of mRNA-1273 and BNT162b2, respectively. Among the weighted population, the median age was 69 years (interquartile range, 66-74), 53 % were female, and 46 % were commercially insured. COVID-19 hospitalization rates per 1000 person-years (PYs) were 5.61 (95 % CI, 5.13-6.09) for mRNA-1273 and 7.06 (95 % CI, 6.54-7.57) for BNT162b2 (HR, 0.82; 0.69-0.98). Medically attended COVID-19 rates per 1000 PYs (95 % CI) were 95.05 (95 % CI, 93.03-97.06) for mRNA-1273 and 106.55 (95 % CI, 104.53-108.57) for BNT162b2 (HR, 0.93; 0.89-0.98). CONCLUSIONS: Results from this observational comparative VE database study provide evidence that among older adults, a third dose of mRNA-1273 was more effective in preventing breakthrough COVID-19 hospitalization and medically attended COVID-19 infection compared with a third dose of BNT162b2.

Immunogenicity of mRNA-1273 and BNT162b2 in Immunocompromised Patients: Systematic Review and Meta-analysis Using GRADE.

INTRODUCTION: Immunocompromised (IC) patients mount poor immune responses to vaccination. Higher-dose coronavirus disease 2019 (COVID-19) vaccines may offer increased immunogenicity. METHODS: A pairwise meta-analysis of 98 studies reporting comparisons of mRNA-1273 (50 or 100 mcg/dose) and BNT162b2 (30 mcg/dose) in IC adults was performed. Outcomes were seroconversion, total and neutralizing antibody titers, and cellular immune responses. RESULTS: mRNA-1273 was associated with a significantly higher seroconversion likelihood [relative risk, 1.11 (95% CI, 1.08, 1.14); P < 0.0001; I2 = 66.8%] and higher total antibody titers [relative increase, 50.45% (95% CI, 34.63%, 66.28%); P < 0.0001; I2 = 89.5%] versus BNT162b2. mRNA-1273 elicited higher but statistically nonsignificant relative increases in neutralizing antibody titers and cellular immune responses versus BNT162b2. CONCLUSION: Higher-dose mRNA-1273 had increased immunogenicity versus BNT162b2 in IC patients.