[Pharmacoeconomic evaluation of the tixagevimab and cilgavimab combination using for pre-exposure prophylaxis of COVID-19].

AIM: To evaluate pharmacoeconomic feasibility using of the tixagevimab and cilgavimab combination for pre-exposure prophylaxis of COVID-19 in immunocompromised patients. MATERIALS AND METHODS: Cost-effectiveness of tixagevimab and cilgavimab in persons ≥12 years old who weigh ≥40 kg and have either a history of allergy that prevents their vaccination against COVID-19 or moderate or immunocompromised was assessed based on PROVENT phase III study results. The quantity of life years or quality-adjusted life years gained was calculated. Direct medical cost associated with prophylaxis of COVID-19, treatment of infected patients and those experiencing long COVID post infection were assessed. Results were compared with wiliness-to-pay threshold, measured as tripled gross domestic product per capita and equal to 2.69 mln RUB in 2022. RESULTS: Pre-exposure prophylaxis of COVID-19 results in additional 0.0287 life years or 0.0247 quality-adjusted life years. The cost of additional life year gained is equal to 1.12 mln RUB, the cost of additional quality-adjusted life years is 1.30 mln RUB. Both costs of additional life year and cost of quality-adjusted life years appeared to be significantly less compared to wiliness-to-pay threshold. CONCLUSION: Pre-exposure prophylaxis of COVID-19 with combination of tixagevimab and cilgavimab is economically feasible and may be recommended for wide use in Russian healthcare system.

[Pre-exposure prophylaxis of new COVID-19 coronavirus infection with tixagevimab/cilgavimab in adult Moscow patients with primary immunodeficiencies].

BACKGROUND: Primary immunodeficiencies (PIDs), now known as inborn errors of immunity, are a group of inherited diseases caused by defects in the genes that control the immune response. Patients with PIDs have risks of developing a severe course and/or death in COVID-19. Passive immunization with long-acting monoclonal antibodies (MABs) to SARS-CoV-2 should be considered as pre-exposure prophylaxis in patients with PIDs. Tixagevimab/cilgavimab is a combination of MABs that bind to the SARS-CoV-2 spike protein. AIM: To evaluate the efficacy and safety of pre-exposure prophylaxis of new SARS-CoV-2 infection in PIDs with the combination of tixagevimab/cilgavimab. MATERIALS AND METHODS: Forty eight patients diagnosed with PIDs were included in the study. Median follow-up after drug administration was 174 days. The total number of confirmed coronavirus infections in patients with PIDs as well as 6 months before and after administration of MAT were assessed. RESULTS: In the analyzed cohort, the overall incidence of COVID-19 from pandemic onset to MABs administration was 75% (36/48), with 31% (11/36) of over-infected patients having had the infection more than once. The incidence of COVID-19 immediately 6 months before the introduction of tixagevimab/cilgavimab was 40%. All patients who had COVID-19 after pre-exposure prophylaxis had a mild infection. The incidence of COVID-19 6 months after tixagevimab/cilgavimab administration significantly decreased compared to the incidence 6 months before administration (7 and 40%, respectively; p<0.001). CONCLUSION: The use of tixagevimab/cilgavimab in patients with PIDs is effective as pre-exposure prophylaxis and reduces the risk of severe COVID-19.

Achieving the "Ending the HIV Epidemic in the U.S." incidence reduction goals among at-risk populations in the South.

INTRODUCTION: Antiretroviral medication coverage remains sub-optimal in much of the United States, particularly the Sothern region, and Non-Hispanic Black or African American persons (NHB) continue to be disproportionately impacted by the HIV epidemic. The "Ending the HIV Epidemic in the U.S." (EHE) initiative seeks to reduce HIV incidence nationally by focusing resources towards the most highly impacted localities and populations. This study evaluates the impact of hypothetical improvements in ART and PrEP coverage to estimate the levels of coverage needed to achieve EHE goals in the South. METHODS: We developed a stochastic, agent-based network model of 500,000 individuals to simulate the HIV epidemic and hypothetical improvements in ART and PrEP coverage. RESULTS: New infections declined by 78.6% at 90%/40% ART/PrEP and 94.3% at 100%/50% ART/PrEP. Declines in annual incidence rates surpassed 75% by 2025 with 90%/40% ART/PrEP and 90% by 2030 with 100%/50% ART/PrEP coverage. Increased ART coverage among NHB MSM was associated with a linear decline in incidence among all MSM. Declines in incidence among Hispanic/Latino and White/Other MSM were similar regardless of which MSM race group increased their ART coverage, while the benefit to NHB MSM was greatest when their own ART coverage increased. The incidence rate among NHB women declined by over a third when either NHB heterosexual men or NHB MSM increased their ART use respectively. Increased use of PrEP was associated with a decline in incidence for the groups using PrEP. MSM experienced the largest absolute declines in incidence with increasing PrEP coverage, followed by NHB women. CONCLUSIONS: Our analysis indicates that it is possible to reach EHE goals. The largest reductions in HIV incidence can be achieved by increasing ART coverage among MSM and all race groups benefit regardless of differences in ART initiation by race. Improving ART coverage to > 90% should be prioritized with a particular emphasis on reaching NHB MSM. Such a focus will reduce the largest number of incident cases, reduce racial HIV incidence disparities among both MSM and women, and reduce racial health disparities among persons with HIV. NHB women should also be prioritized for PrEP outreach.

Characterizing subgroups of sexual behaviors among men who have sex with men eligible for, but not using, PrEP in the Netherlands.

This study identified subgroups of sexual behaviors associated with increased STI/HIV risk among those eligible for but not using pre-exposure prophylaxis (PrEP) in order to improve PrEP uptake and prioritization in the context of restricted capacity. We used data from sexual health centers (SHCs) in the Netherlands, including all visits of eligible but non-PrEP using men who have sex with men (MSM), men who have sex with men and women (MSMW) and transgender persons between July 2019 (start of the Dutch national PrEP pilot (NPP)) and June 2021. Using latent class analysis (LCA), we identified classes of sexual behaviors (number of partners, chemsex, group sex and sex work) and explored whether these classes were associated with STI diagnosis and sociodemographics. Across 45,582 visits of 14,588 eligible non-PrEP using individuals, the best fitting LCA model contained three classes of sexual behaviors. Classes were distinguished by seldomly reported sexual behaviors (class 1; 53.5%, n = 24,383), the highest proportions of ≥6 partners and group sex (class 2; 29.8%, n = 13,596), and the highest proportions of chemsex and sex work (class 3; 16.7% of visits, n = 7,603). Visits in classes 2 and 3 (vs. class 1) were significantly more often with individuals who were diagnosed with an STI, older (≥36 vs. ≤35 years), MSMW (vs. MSM), and visiting an urban (vs. non-urban) SHC; while these visits were significantly less often with individuals from an STI/HIV endemic area. The percentage of visits at which an STI was diagnosed was 17.07% (n = 4,163) in class 1, 19.53% (n = 2,655) in class 2 and 25.25% (n = 1,920) in class 3. The highest risk of STI, and thereby HIV, was in those engaging in specific subgroups of sexual behavior characterized by frequently reporting multiple partners, group sex, sex work or chemsex. PrEP uptake should be encouraged and prioritized for these individuals.

Impact of the Early COVID-19 Pandemic on the Number of HIV Preexposure Prophylaxis Uses and the Proportion of Preexposure Prophylaxis Users Receiving Sexually Transmitted Infection Testing Services.

BACKGROUND: With the potential impact of the COVID-19 pandemic on HIV preexposure prophylaxis (PrEP) care management, we assessed the number of PrEP users and sexually transmitted infection (STI) testing-eligible PrEP users, STI testing rates, and prevalence between prepandemic (January 1, 2018-March 31, 2020) and early-pandemic (April 1, 2020-September 30, 2020) periods. METHODS: In this retrospective cohort study, a PrEP user for a given quarter is defined as either a previous PrEP user or a PrEP initiator who has at least 1-day coverage of tenofovir/emtricitabine in the given quarter. The STI testing-eligible PrEP users for a given quarter were defined as those persons whose runout date (previous dispense date + days of tenofovir/emtricitabine supply) was in the given quarter. RESULTS: The quarterly number of PrEP users increased from the first quarter of 2018 to the first quarter of 2020 and then decreased in the second and third quarter of 2020. Among STI testing-eligible PrEP users who had ≤14 days between runout and next refill date, gonorrhea and chlamydia screening testing rates were 95.1% for prepandemic and 93.4% for early pandemic ( P = 0.1011). Among all STI testing-eligible PrEP users who were tested for gonorrhea and chlamydia, gonorrhea prevalence was 6.7% for prepandemic and 5.7% for early pandemic ( P = 0.3096), and chlamydia prevalence was 7.0% for prepandemic and 5.8% for early pandemic ( P = 0.2158). CONCLUSIONS: Although the early COVID-19 pandemic resulted in lower numbers of PrEP users and PrEP initiators, individuals who remained continuous users of PrEP maintained extremely high rates of bacterial STI screening. With high STI prevalence among PrEP users, assessments of PrEP care management are continuously needed.

Impacts of COVID-19 on sexual behaviors, HIV prevention and care among men who have sex with men: A comparison of New York City and Metropolitan Atlanta.

The COVID-19 pandemic has disrupted HIV prevention, care, and transmission opportunities. This likely varies by geography, given differences in COVID-19 burden and mandates over time, and by age, given different likelihoods of severe COVID-19 consequences. We consider changes in sexual behavior, HIV testing, pre-exposure prophylaxis (PrEP) use and antiretroviral therapy (ART) use among men who have sex with men (MSM) over the first year of the COVID-19 epidemic, comparing the Atlanta metropolitan area and New York City (NYC). We use two continuous time-series datasets and one panel dataset, assessing changes over time within city and comparing across cities, and disaggregate major findings by age. For clinical results, ART use showed by far the smallest reductions, and testing the largest. Disruptions occurred concurrently between cities, despite the major wave of COVID-19, and government mandates, occurring later in Atlanta. Test positivity increased in NYC only. In both cities, younger MSM saw the greatest reductions in testing and PrEP use, but the smallest in sexual behavior. Reduced clinical service usage would be unconcerning if stemming solely from reductions in exposure; however, the patterns for young MSM suggest that the COVID-19 epidemic likely generated new conditions for increased HIV transmission, especially in this cohort.

Impact and cost-effectiveness of the national scale-up of HIV pre-exposure prophylaxis among female sex workers in South Africa: a modelling analysis.

INTRODUCTION: In 2016, South Africa (SA) initiated a national programme to scale-up pre-exposure prophylaxis (PrEP) among female sex workers (FSWs), with ∼20,000 PrEP initiations among FSWs (∼14% of FSW) by 2020. We evaluated the impact and cost-effectiveness of this programme, including future scale-up scenarios and the potential detrimental impact of the COVID-19 pandemic. METHODS: A compartmental HIV transmission model for SA was adapted to include PrEP. Using estimates on self-reported PrEP adherence from a national study of FSW (67.7%) and the Treatment and Prevention for FSWs (TAPS) PrEP demonstration study in SA (80.8%), we down-adjusted TAPS estimates for the proportion of FSWs with detectable drug levels (adjusted range: 38.0-70.4%). The model stratified FSW by low (undetectable drug; 0% efficacy) and high adherence (detectable drug; 79.9%; 95% CI: 67.2-87.6% efficacy). FSWs can transition between adherence levels, with lower loss-to-follow-up among highly adherent FSWs (aHR: 0.58; 95% CI: 0.40-0.85; TAPS data). The model was calibrated to monthly data on the national scale-up of PrEP among FSWs over 2016-2020, including reductions in PrEP initiations during 2020. The model projected the impact of the current programme (2016-2020) and the future impact (2021-2040) at current coverage or if initiation and/or retention are doubled. Using published cost data, we assessed the cost-effectiveness (healthcare provider perspective; 3% discount rate; time horizon 2016-2040) of the current PrEP provision. RESULTS: Calibrated to national data, model projections suggest that 2.1% of HIV-negative FSWs were currently on PrEP in 2020, with PrEP preventing 0.45% (95% credibility interval, 0.35-0.57%) of HIV infections among FSWs over 2016-2020 or 605 (444-840) infections overall. Reductions in PrEP initiations in 2020 possibly reduced infections averted by 18.57% (13.99-23.29). PrEP is cost-saving, with $1.42 (1.03-1.99) of ART costs saved per dollar spent on PrEP. Going forward, existing coverage of PrEP will avert 5,635 (3,572-9,036) infections by 2040. However, if PrEP initiation and retention doubles, then PrEP coverage increases to 9.9% (8.7-11.6%) and impact increases 4.3 times with 24,114 (15,308-38,107) infections averted by 2040. CONCLUSIONS: Our findings advocate for the expansion of PrEP to FSWs throughout SA to maximize its impact. This should include strategies to optimize retention and should target women in contact with FSW services.

PrEP disclosure and discussions within social networks of people who inject drugs experiencing homelessness: a brief report.

BACKGROUND: In the context of increasing injection-related HIV outbreaks across the United States, particularly among people who inject drugs (PWID) experiencing homelessness, there is an urgent need to expand access to pre-exposure prophylaxis (PrEP) for HIV prevention. Peer-based interventions for PrEP could be helpful for promoting PrEP uptake, yet the social experiences of using PrEP among PWID experiencing homelessness have not been thoroughly explored. METHODS: To better understand social experiences surrounding PrEP use among PWID experiencing homelessness, we conducted qualitative interviews from March-December 2020 with current and former PrEP patients of an innovative, low-threshold program implemented by Boston Health Care for the Homeless Program (BHCHP) in Boston, MA. Thematic analysis of coded interview data explored participants' perspectives and experiences with PrEP disclosure and discussions within their social networks. RESULTS: Among interviews with 21 participants, we identified the following four interrelated aspects of their social experiences using PrEP: (1) participants' were aware of increasing HIV transmission within their social networks, which motivated their PrEP use and disclosure; (2)  participants generally avoided disclosing their PrEP use within public spaces or casual conversations; (3)  participants expressed greater willingness to discuss PrEP with their close social contacts; and (4)  some participants self-identified as leaders or expressed interest in leading the dissemination of PrEP information within their social networks. CONCLUSIONS: Findings highlight the significance of PrEP disclosure and discussions within the social networks of PWID experiencing homelessness, suggesting a need for continued social network and intervention research-particularly to establish the feasibility and acceptability of peer-based interventions for promoting PrEP-with this marginalized population.

Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial Healthcare Worker Exposure Response and Outcomes of Hydroxychloroquine (HERO-HCQ).

OBJECTIVES: To determine whether hydroxychloroquine (HCQ) is safe and effective at preventing COVID-19 infections among health care workers (HCWs). METHODS: In a 1: 1 randomized, placebo-controlled, double-blind, parallel-group, superiority trial at 34 US clinical centers, 1360 HCWs at risk for COVID-19 infection were enrolled between April and November 2020. Participants were randomized to HCQ or matched placebo. The HCQ dosing included a loading dose of HCQ 600 mg twice on day 1, followed by 400 mg daily for 29 days. The primary outcome was a composite of confirmed or suspected COVID-19 clinical infection by day 30, defined as new-onset fever, cough, or dyspnea and either a positive SARS-CoV-2 polymerase chain reaction test (confirmed) or a lack of confirmatory testing due to local restrictions (suspected). RESULTS: Study enrollment closed before full accrual due to recruitment challenges. The primary end point occurred in 41 (6.0%) participants receiving HCQ and 53 (7.8%) participants receiving placebo. No difference in the proportion of participants experiencing clinical infection (estimated difference of -1.8%, 95% confidence interval -4.6-0.9%, P = 0.20) was identified nor any significant safety issues. CONCLUSION: Oral HCQ taken as prescribed appeared safe among HCWs. No significant clinical benefits were observed. The study was not powered to detect a small but potentially important reduction in infection. TRIAL REGISTRATION: NCT04334148.

Process description of developing HIV prevention monitoring indicators for a province-wide pre-exposure prophylaxis (PrEP) program in British Columbia, Canada.

In 2018, the pre-exposure prophylaxis (PrEP) program was initiated in British Columbia (BC), Canada, providing PrEP at no cost to qualifying residents. This observational study discussed the steps to develop key evidence-based monitoring indicators and their calculation using real-time data. The indicators were conceptualized, developed, assessed and approved by the Technical Monitoring Committee of representatives from five health authority regions in BC, the BC Ministry of Health, the BC Centre for Disease Control, and the BC Centre for Excellence in HIV/AIDS. Indicator development followed the steps adopted from the United States Centers for Disease Control and Prevention framework for program evaluation in public health. The assessment involved eight selection criteria: data quality, indicator validity, existing scientific evidence, indicator informativeness, indicator computing feasibility, clients' confidentiality maintenance capacity, indicator accuracy, and administrative considerations. Clients' data from the provincial-wide PrEP program (January 2018-December 2020) shows the indicators' calculation. The finalized 14 indicators included gender, age, health authority, new clients enrolled by provider type and by the health authority, new clients dispensed PrEP, clients per provider, key qualifying HIV risk factor(s), client status, PrEP usage type, PrEP quantity dispensed, syphilis and HIV testing and incident cases, and adverse drug reaction events. Cumulative clients' data (n = 6966; 99% cis-gender males) identified an increased new client enrollment and an unexpected drop during the COVID-19 pandemic. About 80% dispensed PrEP from the Vancouver Coastal health authority. The HIV incidence risk index for men who have sex with men score ≥10 was the most common qualifying risk factor. The framework we developed integrating indicators was applied to monitor our PrEP program, which could help reduce the public health impact of HIV.

Real-world experience of tixagevimab-cilgavimab pre-exposure prophylaxis in orthotopic heart transplant recipients.

BACKGROUND: Pre-exposure prophylaxis with tixagevimab-cilgavimab (tix-cil) may be associated with cardiovascular adverse events. Also, in vitro studies have reported a reduced activity of tix-cil against emerging SARS-CoV-2 Omicron subvariants. Our study aimed to report the real-world outcomes of tix-cil prophylaxis in orthotopic heart transplant (OHT) recipients METHODS: We retrospectively studied all OHT recipients who received one dose of tix-cil (150-150 mg or 300-300 mg) at Mayo Clinic in Arizona, Florida, and Minnesota, between February 5, 2022 and September 8, 2022. We collected data on cardiovascular adverse events and breakthrough COVID-19 following tix-cil administration. RESULTS: One hundred sixty-three OHT recipients were included. The majority were male (65.6%), and the median age was 61 years (IQR 48, 69). During the median follow-up of 164 days (IQR 123, 190), one patient presented an episode of asymptomatic hypertensive urgency that was managed with outpatient antihypertensive treatment optimization. Twenty-four patients (14.7%) experienced breakthrough COVID-19 at the median of 63.5 days (IQR 28.3, 101.3) after tix-cil administration. The majority (70.8%) completed the primary vaccine series and received at least one booster dose (70.8%). Only one patient with breakthrough COVID-19 required hospitalization. All patients survived. CONCLUSIONS: In this cohort of OHT recipients, no patients developed severe cardiovascular events related to tix-cil. The high incidence of breakthrough COVID-19 could be due to the reduced activity of tix-cil against current circulating SARS-CoV-2 Omicron variants. These results emphasize the need for a multimodal prevention strategy against SARS-CoV-2 in these high-risk patients.

Financing and Delivering Pre-Exposure Prophylaxis (PrEP) to End the HIV Epidemic.

The U.S. has the tools to end the HIV epidemic, but progress has stagnated. A major gap in U.S. efforts to address HIV is the under-utilization of medications that can virtually eliminate acquisition of the virus, known as pre-exposure prophylaxis (PrEP). This document proposes a financing and delivery system to unlock broad access to PrEP for those most vulnerable to HIV acquisition and bring an end to the HIV epidemic.

INTRODUCTION Disrupting the Status Quo: Building Equitable Access to HIV PrEP in the US through Innovative Financing.

This special edition of JLME centers on a novel proposal for a national PrEP access program with the potential to break through a failed status quo.

Health Departments and PrEP: A Missed Opportunity for Public Health.

The paper identifies common barriers and challenges to Pre-Exposure Prophylaxis (PrEP) uptake and offers considerations for state and local public health departments to address barriers and retool infrastructure to increase access to PrEP to new users. Authors identify synergistic opportunities with federal agencies and funders to advance PrEP-related HIV prevention efforts, that prioritize strategies and investments to provide PrEP to people who could benefit from the intervention but are unaware of PrEP or struggle to access it. Barriers discussed and examined include financing strategies to reduce financial burden of PrEP medication, expanding PrEP access and outreach beyond clinical settings, and increasing the network and reach of the provider community to serve people we oppress through policy choices and discourses of racial and socioeconomic inferiority.

Pre-exposure Prophylaxis Persistence at a Diverse Sexual Health Clinic: Comparison of the pre-COVID-19 era to the COVID-19 era.

The COVID-19 pandemic interrupted health care delivery and exacerbated disparities. Many sexual health clinics transitioned to telemedicine, including for pre-exposure prophylaxis (PrEP). We conducted a retrospective cohort study of patients at an urban sexual health clinic to assess the likelihood and predictors of PrEP persistence in the year following PrEP initiation. We compared patients starting PrEP in the four months preceding the first COVID surge to those starting PrEP one year prior. We found lower PrEP persistence in the COVID cohort compared to the pre-COVID cohort (50.8% vs. 68.9%, respectively). In both cohorts, most care was provided through in-person visits and telemedicine was rare. In the pre-COVID cohort, older patients and those identifying as non-Hispanic White were more likely to persist on PrEP. In the COVID cohort, these disparities in PrEP persistence were not observed. Flexible models of care may facilitate equitable care engagement and re-engagement.

Masibambane-Ladies Chat: Developing an Online Gender-Enhanced PrEP Information-Motivation Workshop for Young South African Women.

This article describes the processes of transforming an in-person group-based intervention to promote uptake of PrEP among young woman in South Africa to an online interactive "workshop" during the COVID-19 pandemic. Beginning in person and continuing virtually, we used a step-by-step participatory approach with multiple stakeholder groups to develop nine activities to increase knowledge about, as well as motivation and intention to take PrEP, and to address gender-based barriers to PrEP. Activities were informed by our theoretical framework and formative work with young women ages 18-25. We demonstrate how we developed a gender-enhanced online PrEP workshop that was interactive, group-based, and in accordance with elements of established successful intervention design; why WhatsApp emerged as the most accessible application for the young women in our workshop; and how an intervention with a hybrid approach-alternating between chat box and live sessions-combined with verbal, written, and emoji-based communication enabled interaction among participants.