COVID-19 pre-exposure prophylaxis with tixagevimab/cilgavimab in patients with haematological malignancy: A single-centre experience

Background: COVID-19 pandemic still pose a substantial threat worldwide despite increasing vaccine availability. Patients with haematological malignancies have been shown to have increased risk of contracting COVID-19 and are more susceptible to develop severe illness from SARS-CoV- 2 infection. The immune response to vaccines is impaired in patients with haematological malignancy due to underlying disease or antineoplastic therapies. The monoclonal-antibody combination, Evusheld is composed of tixagevimab and cilgavimab, two neutralising antibodies against SARS-CoV- 2. It has been shown to be safe and have efficacy for the prevention of COVID-19. Our aim of study is to describe the incidence and outcome of breakthrough COVID-19 infection among patients who received Evusheld in our centre and analyse the factors that possibly increase the risk of breakthrough infection. Material(s) and Method(s): A retrospective review of all adult patients with haematological malignancy who received tixagevimab/ cilgavimab 150/150 mg injection in Hospital Pulau Pinang from 1 July 2022 to 31 August 2022 with a follow-up period to 30 November 2022 was conducted. Demographic data, clinical characteristics and outcome will be retrieved from patient's medical records. Data were analysed using Statistical Package for Social Sciences software (version 21.0). Result(s): A total of 96 patients (50 males and 46 females) received tixagevimab/cilgavimab injection during the study period with a median age of 61 years (range 19-82). Majority of them were diagnosed with multiple myeloma (42.7%), followed by lymphoma (33.3%) and leukaemia (24%). One third of them had history of therapy with monoclonal antibody and 20% had haematopoietic stem cell transplantation. No major adverse effects of tixagevimab/cilgavimab injection were noted among the study population. Of the 12 patients (12.5%) who had COVID-19 infection, all of them had mild infection;three were asymptomatic and six patients received Paxlovid antiviral therapy. The median time from tixagevimab/cilgavimab to the onset of COVID-19 infection was 35 days (range 5-97 days). The mean age of patients with breakthrough COVID-19 infection were older compared to those without breakthrough infection but was not statistically significant. The incidence of breakthrough COVID-19 infection was not affected by type of haematological malignancy, history of monoclonal antibody therapy or COVID-19 vaccination. Discussion and Conclusion(s): Our findings showed that tixagevimab/cilgavimab was safe and effective in preventing COVID-19- related morbidity and mortality among patients with haematological malignancy during the study period. However, the limitation is the lack of access to whole genome sequencing for detection of resistant variants for breakthrough infections.

EXPERIENCE WITH TIXAGEVIMAB AND CILGAVIMAB (EVUSHELD) IN 86 RHEUMATIC PATIENTS UNDERGOING ANTI-B CELL THERAPY WITH RITUXIMAB.

The problem of prevention of coronavirus disease 2019 (COVID-19) in patients with immune-mediated inflammatory rheumatic diseases (IMRD) remains highly relevant. The presence of IRD is associated with a high risk of disease and severe course of COVID-19 during immunosuppressive treatment, primarily anti-B cell therapy with rituximab (RTX), and a low level of post-vaccination response in such patients. A new strategy for the prevention and treatment of COVID-19 are virus-neutralizing monoclonal antibodies to coronavirus;currently, combined long-acting monoclonal antibodies tixagevimab and cilgavimab (Evusheld) are registered for prevention in the world and the Russian Federation. . Tixagevimab and cilgavimab (TC) show neutralizing activity against SARS-CoV-2, including the Omicron strain, primarily its variants BA.4, BA.5, BA.2.75 ("Centaur"). Objective - to evaluate the efficacy and safety of TC for pre-exposure prophylaxis of COVID-19 in rheumatic patients receiving RTX, based on a prospective observational study. Materials and methods. The main group included 86 patients with various IMRD receiving RTX: 50 of them had ANCA-associated systemic vasculitis (AAV), 15 - rheumatoid arthritis, 9 - Sjogren's syndrome (SS), 4 - IgG4-related disease, 3 - systemic lupus erythematosus (SLE), 3 - dermatomyositis (DM), 2 - systemic scleroderma (SSD). Median age was 59 (19-82) years;male: female ratio - 1:1,8. From March 26 to August 30 2022, patients received a single intramuscular injection of TC in a total dose of 300 mg, mainly after RTX (in 52% of cases, in 28% on the next day after RTX). The control group included 42 patients with AAV (median age - 45 (35-71) years;male: female ratio - 1:1), also treated with RTX, who did not receive pre-exposure prophylaxis of TC. The duration of observation was 7 months, until November 1 2022. At this time, 98% of confirmed cases of coronavirus in the Russian Federation were Omicron. A telephone and/or online survey of patient has been conducted to detect cases of COVID-19 and adverse reactions. Results. In the TC group, confirmed coronavirus infection have been detected in 17 (20%) patients (AAV - 10, SS - 3, SSD - 2, SLE - 1, DM - 1), with fever in 7 (8%), only in one case hospitalization was required (lung damage was not detected in computed tomography), in two cases, according to CT mild lung damage (CT 1-2), there were no deaths. Good TC's tolerability was noted, signs not associated with COVID-19 or progression of IMRD after administration of TC were observed in 8 (9%) patients (GPA - 3 MPA - 1, RA - 2, SLE - 1, IgG4-related disease - 1), adverse reactions definitely associated with the use of TC were not found. The most serious event not associated with coronavirus infection was the progression of polyneuropathy in a patient with RA. In the control group, 3 (7%) patients were diagnosed with COVID-19, one with severe lung injury (CT 3, pulmonary embolism) and death. Conclusions. The data of clinical studies and our own clinical experience evidence the effectiveness of the use of a combination of long-acting monoclonal antibodies TC (Evusheld), registered for indications for pre-exposure prophylaxis and treatment of COVID-19. Patients with IMRD treated with RTX have a favorable safety profile of TC. The introduction of virus-neutralizing monoclonal antibodies, a new drug class for the prevention and treatment of infectious diseases, opens significant prospects for improving the prognosis of patients with IRD.Copyright © 2023 Ima-Press Publishing House. All rights reserved.

[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 the Impact of the COVID-19 Pandemic on HIV PrEP care: A Review and Synthesis of the Literature.

The global COVID-19 pandemic and associated lockdown measures have caused disruptions to sexual health services and created additional barriers to the continuity of HIV pre-exposure prophylaxis (PrEP) among key populations. This review provides an examination of the influences of the pandemic on engagement in the PrEP care continuum. Using the PRISMA guideline, 46 studies were included in this review and the synthesis. Most of the studies were conducted in high-income settings through quantitative analysis. A majority of studies examining the changes in PrEP use suggested a decline or discontinuation in PrEP uptake during the pandemic. The most common reasons for stopping using PrEP were perceived barriers to PrEP-related care, having reduced sexual behaviors and fewer sexual partners, and reduced perceived risk of HIV infection. Limited studies documenting an increase in PrEP uptake were all in specific PrEP optimizing programs. During the pandemic, there is also an emerging trend of switching to on-demand PrEP from daily oral PrEP. Future studies should understand the mechanism of strategies that facilitated the improvements during the pandemic. PrEP implementation programs should consider alternative PrEP modalities and provide consistent and comprehensive knowledge about correct information.

Progress towards ending HIV transmission in England by 2030

Background: England is committed to ending HIV transmission by 2030. The HIV Action Plan (2021) set an interim ambition to reduce HIV transmission by 80% to 600 new diagnoses first made in England by 2025. Here we present the progress between 2019 (baseline) and 2021, interpreted in the context of the COVID-19 pandemic. Method(s): People newly diagnosed with HIV were reported to the HIV and AIDS Reporting Section (HARS). The annual number of people having an HIV test in all sexual health services (SHS) including online testing were reported using GUMCAD. HIV diagnoses among people previously diagnosed abroad were excluded (25%). Result(s): New HIV diagnoses first made in England fell by 32% from 2,986 in 2019 to 1,987 in 2020, but plateaued in 2021 (2,023). Among gay/bisexual men, HIV diagnoses plateaued in 2021 (721) after a fall of 45% between 2019 and 2020, from 1,262 to 699. After a fall in HIV testing in 2020 (from 156,631 in 2019 to 144,800 in 2020), the number of people tested in 2021 (178,466) exceeded pre-COVID-19 levels. This suggests a decline in HIV incidence supported by a CD4 back calculation model (80% probability of a decline for the period 2019-2021), but at a slowing rate. Among heterosexual adults, new HIV diagnoses first made in England in 2021 also plateaued (798) following a 31% decrease (from 1,109 in 2019 to 761 in 2020). However, HIV testing coverage has not recovered to pre- COVID-19 levels (628,607 in 2019, 441,017 in 2020 and 489,727 in 2021). This provides no evidence of a fall in incidence in this population. Conclusion(s): A reduction by 360 new diagnoses first made in England year on year from 2022 onwards is required to meet the HIV Action Plan ambition. Despite an estimated 4,500 people with undiagnosed HIV and extremely high levels of antiretroviral therapy and viral suppression, PrEP access remains unequal. HIV testing numbers, which were affected by COVID-19 pandemic, have recovered in gay/bisexual men, but not among heterosexual adults. While the interim ambition is within reach for gay/bisexual men, PrEP and testing levels must be scaled up in heterosexual adults.

BHIVA Spring Conference 2023

The proceedings contain 159 papers. The topics discussed include: microelimination of hepatitis C among people living with diagnosed HIV in England;laboratory implementation of emergency department blood-borne virus (EDBBV) opt-out screening in a London tertiary center;a review of sexual health and blood-borne virus care provided to inmates at admission into UK prisons and secure facilities;implementation of routine opt-out blood-borne virus (BBV) screening in 34 emergency departments (EDs) in areas of extremely high HIV prevalence in England;impact and experiences of offering HIV testing across the whole city population through primary care clusters and GP surgeries in the texting 4 Testing (T4T) project;'Not PrEPared': barriers to accessing PrEP in England;HIV care during the SARS-COV-2 pandemic for Black people with HIV in the UK;clinical presentation of mpox in people with and without HIV;and 'if you don't know, how can you know?': a qualitative investigation of HIV pre-exposure prophylaxis knowledge and perceptions among women in England.

Missed opportunities for pre-exposure prophylaxis (PrEP) and outcomes of people acquiring HIV with previous or recent PrEP use

Background: With NHS PrEP now available for those at risk, we aimed to identify missed opportunities for people newly diagnosed with HIV who attended sexual and reproductive health (SRH) services, and to determine the HIV outcomes associated with people acquiring HIV with previous or recent PrEP use. Method(s): A retrospective observational study reviewed all new HIV diagnoses from the last 2 years to see if they were eligible for PrEP and offered in SRH services. Data was collected using electronic medical records on HIV outcomes - virological suppression, resistance and antiretroviral choice. Result(s): There were 74 new HIV diagnoses. 41 people were eligible but only 10 were known to have accessed PrEP at our services. 21% were heterosexual and of black ethnicity - it was not possible to ascertain whether they were eligible for PrEP from the notes. Of the 10 people with recent PrEP use, 2 stopped due to side effects;headaches, vomiting, fatigue and renal toxicity concerns. For the remaining adherence concerns were reported - taking event based dosing (EBD) incorrectly and difficulty accessing services. 80% of people achieved virological suppression. 90% were put on a second generation integrase or protease inhibitor. No one developed nucleoside reverse transcriptase inhibitor (NRTI) resistance. 6 people eligible for PrEP had attended SRH services but not given PrEP. 2 attended during the IMPACT trial being full and referred to IwantPrEPnow. 2 attended during COVID where baseline bloods were done with follow up but subsequently tested positive. 2 people refused PrEP with 1 deeming themselves to be low risk. Conclusion(s): Our data highlights several missed opportunities for starting same-day PrEP which potentially may have prevented HIV acquisition. If PrEP is not issued on the day, adequate follow up must be ensured. Reassuringly those who acquired HIV with recent PrEP use have achieved good virological control without NRTI mutations. Counselling on potential side effects, EBD dosing and ongoing HIV risk are essential. Despite NHS PrEP available over 2 years, our data shows we are still failing to meet the demand of PrEP not only in men who have sex with men but also in other key at risk groups.

Hiv Self-Testing in Vietnam: From Pilot to Scale Up

While the World Health Organization strongly recommends HIV self-testing (HIVST) as an approach to HIV testing services, scale up has been minimal in low- and middle-income countries. Vietnam has successfully delivered HIVST at scale for key populations (KP), including men who have sex with men, transgender women, people who inject drugs, female sex workers and their partners. We reviewed data from the USAID/PATH Healthy Markets (2014-2021), including consumer surveys, HIVST usability and performance assessments, and service data to summarize the five stages of HIVST scale-up in Vietnam: 1) Assessing HIVST acceptability, preferences, and willingness to pay (WTP);2) Piloting HIVST;3) Developing HIVST policies and assessing products;4) Facilitating HIVST market authorization;and 5) Implementing differentiated service models. A '5A' approach was employed to shape HIVST markets, i.e., improving affordability, enhancing availability, assuring quality, ensuring appropriate design, and boosting awareness and demand. We assessed key factors related to HIVST supply and demand. In terms of supply, the median price people were willing to pay was US$4.3 per test. HIVST products with stringent regulatory approval successfully obtained free sale certificate registration, and blood-based HIVST products were highly accurate (99%-99.8%). Differentiated HIVST distribution models played a significant role in scaling-up HIVST and ensuring uninterrupted access to essential HIV services, e.g., pre-exposure prophylaxis monitoring during COVID-19 lock-downs. Related to demand and testing uptake, the majority of KPs accessing HIVST were first time HIV testers. Creative online-to-offline behavior change communication increased client awareness, trust, and use of HIVST. HIVST was successful in reaching first-time testers who may not otherwise test or seek facility-based care. HIVST is an effective strategy for reaching undiagnosed individuals and is accepted and preferred by KPs. HIVST scale-up requires enabling policy, intensive demand generation efforts, and differentiated service models.Copyright © 2023

Low incidence of HIV infection and decreasing incidence of sexually transmitted infections among PrEP users in 2020 in Germany.

INTRODUCTION: Objectives of this study, as part of a nation-wide HIV pre-exposure prophylaxis (PrEP) evaluation project, were to determine the incidence of infections with HIV, chlamydia, gonorrhea, syphilis, hepatitis A/B/C in persons using PrEP, and to describe the health care funded PrEP use in Germany. Additionally, factors associated with chlamydia/gonorrhea and syphilis infections were assessed. METHODS: Anonymous data of PrEP users were collected at 47 HIV-specialty centers from 09/2019-12/2020. Incidence rates were calculated per 100 person years (py). Using longitudinal mixed models, we analyzed risk factors associated with sexually transmitted infections (STIs). RESULTS: 4620 PrEP users were included: 99.2% male, median age 38 years (IQR 32-45), 98.6% men who have sex with men (MSM). The median duration of PrEP exposure was 451 days (IQR 357-488), totaling 5132 py. Four HIV infections were diagnosed, incidence rate 0,078/100py (95% CI 0.029-0.208). For two, suboptimal adherence was reported and in the third case, suboptimal adherence and resistance to emtricitabine were observed. One infection was likely acquired before PrEP start. Incidence rates were 21.6/100py for chlamydia, 23.7/100py for gonorrhea, 10.1/100py for syphilis and 55.4/100py for any STI and decreased significantly during the observation period. 65.5% of syphilis, 55.6% of chlamydia and 50.1% of gonorrhea cases were detected by screening of asymptomatic individuals. In a multivariable analysis among MSM younger age, PrEP start before health insurance coverage and daily PrEP were associated with greater risk for chlamydia/gonorrhea. Symptom triggered testing and a history of STI were associated with a higher risk for chlamydia/gonorrhea and syphilis. A significantly lower risk for chlamydia/gonorrhea and syphilis was found for observations during the COVID-19 pandemic period. CONCLUSIONS: We found that HIV-PrEP is almost exclusively used by MSM in Germany. A very low incidence of HIV infection and decreasing incidence rates of STIs were found in this cohort of PrEP users. The results were influenced by the SARS-CoV-2 pandemic. Rollout of PrEP covered by health insurance should be continued to prevent HIV infections. Increased PrEP availability to people at risk of HIV infection through the elimination of barriers requires further attention. Investigation and monitoring with a longer follow-up would be of value.

Evolution of Clusters Transmission Patterns in France during the Last Decade

Background: The recent transmission clusters (RTCs) identified through phylogenetic approaches allow to describe the main transmission networks. This render possible to describe potential shifts among HIV transmission routes and populations and, in some cases, to specifically target prevention measures. Here we describe the evolution of RTCs over the last decade in a specialized laboratory serving centers from the entire French territory. Method(s): We extracted all the HIV reverse transcriptase sequences available between 01/01/2013 and 31/08/2022. The sequences dataset was studied overall and divided into three equal time periods: 2013-15, 2016-18, 2019-2021. The first sequences available for each patient were aligned and the trees were reconstructed by maximum likelihood using IQtree software. Clusters, defined by a maximum genetic distance < 4.5% and a branch support >90%, were extracted using ClusterPicker. Result(s): Overall, 8591 sequences were included. Among them, 950 RTCs were identified including 2492 sequences (29%) and 68 large RTCs ( >4 sequences) with 475 (5.6%) sequences. The mean duration of large RTCs (from the first to the last sequences) was 5.1 years [IQR: 4.1-7.1] and 34 were still active (including at least one sequence during the last year of the study period). 3640, 2897 and 2157 sequences were included for the 2013-15, 2016-18 and 2019-2021 periods, respectively. We identified 298 RTCs (19.5% of sequences), 249 (20.4%) and 226 (27.5%) among those periods, respectively. While the number of sequence pairs decreased from 2013-15 to 2019-21, the number of large RTCs increased steadily (see Table 1). During the period 2019-21, including the largest clusters, patients belonging to a RTC were more often male (68 vs 58%, p< 0.001) and younger (average age: 39 vs 44 years, p< 0.001) than non-RTC patients. This observation was even more marked for very large RTCs (see Table 2). It should be noted that the largest cluster (14 patients) was mainly composed of women and located in French overseas territories. Conclusion(s): This study shows an evolution of the structure of HIV sequence clusters over time with a decreasing number of small RTCs but an increasing number of large RTCs. These trends can be explained by a better global control of transmission, due in part to TasP, but not preventing some super-transmitters networks, despite PrEP use and not only including MSM is some settings. The COVID period does not seem to have strongly prevented such large transmission networks.

SEXUAL BEHAVIOR AND STI INCIDENCE DURING THE FIRST 4 YEARS OF PrEP USE AMONG MSM

Background: A prospective demonstration project in Amsterdam (AMPrEP) provided pre-exposure prophylaxis (PrEP) to people vulnerable to HIV in 2015- 2020. Data on long-term trends in sexual behavior and incidence of STIs during PrEP use are needed to inform future PrEP programs. Therefore, we assessed sexual behavior and incidence rates of STIs among MSM and transgender women on PrEP over four years. Method(s): AMPrEP participants chose between oral PrEP daily (dPrEP) or event-driven (edPrEP) at baseline and could switch regimens at each 3-monthly study visit. They were tested for STIs at these visits and if necessary in between. Follow-up began at PrEP initiation and continued until 48 months of follow-up or was censored at March 15, 2020 (start COVID-19), whichever occurred first. We assessed changes over time in incidence rates (IR) of chlamydia, gonorrhea, and infectious syphilis using Poisson regression. We estimated the IR of Hepatitis C (HCV) diagnoses per consecutive year. We described the number of HIV diagnoses, and sexual behavior (i.e. number of sex partners, condomless anal sex acts with casual partners [CAS]). Result(s): A total of 367 (365 MSM) started PrEP and contributed 1249 person-years of observation. IRs of any STI was 87[95%CI 82-93]/100PY. There was no change in the IR of any STI and infectious syphilis over time on PrEP. We observed a slight decrease in incident chlamydia and gonorrhea in daily PrEP users (Table). Two incident HIV cases were diagnosed in the first year of follow-up. IRs for HCV were 1.5[0.6-3.6], 2.5[1.3-5.0], 0.7[0.2-2.7], and 0.4[0.1- 2.8]/100PY, per consecutive year on PrEP. Median number of sex partners per 3-month period decreased from 16[IQR 8-34] and 12[6-25] (dPrEP and edPrEP, respectively) at baseline, 15[7-30] and 8[3-16] at 24 months, and 12[6-26] and 5[2-12] at 48 months. Median number of CAS acts with casual partners were respectively 7[3-15] and 4[1-9] at baseline, 14[5-25] and 4[1-12] at 24 months, and 12[4-25] and 4[1-9] at 48 months. Conclusion(s): Over the first 4 years of PrEP use overall STI incidence was high and stable. Chlamydia and gonorrhea incidence declined slightly in daily users. Numbers of sex partners seemed to decrease in both dPrEP and edPrEP users. Number of CAS acts with casual partners appeared to increase first, and then stabilized. Notably, this did not result in increased incidence of STIs. Regular testing and treatment of STIs remain a priority among PrEP users. Biomedical prevention of STIs can be examined in this context.

Hospitalisation and death in lung transplant recipients following COVID-19 infection

Introduction/Aim: Rates of hospitalisation and death from COVID-19 in lung transplant (LTx) recipients vary internationally. We aimed to assess risk factors for this in an Australian cohort. Method(s): We performed a retrospective cohort study of all LTx recipients between January 2020 and September 2022. LTx recipients with COVID-19 were included. Baseline characteristics and treatments were recorded. Multivariate logistic regression was performed to identify risk factors associated with hospitalisation and death. Result(s): 128/387 (33%) recipients tested positive to SARS-CoV-2 during the study period, 97.6% during the Omicron waves with 40(31.3%) requiring hospitalisation and 10 (7.8%) died. The median (IQR) recipient age was 50.6 (22-77). The cohort was of Caucasian ethnicity 105 (82%), 48% were female with high vaccination rates (98.4%). Chronic lung allograft dysfunction (CLAD) was present in 48 (37.5%). 103 (80.5%) of patients received early SARS-CoV-2 treatment with either Sotrovimab 84(65%), Molnupirivir 50(39%) or combination 31(24%). 25 patients (19.5%) received no early treatment. All hospitalised patients received Remdesivir and Dexamethasone as per local treatment protocols. Regarding risk of hospitalisation, multivariate analysis showed that recipient age (1-unit change OR 1.04 95% CI 1.01-1.07 p = 0.019) was associated with an increased risk, whereas Molnupiravir was protective (OR 0.32 95% CI 0.13-0.80 p = 0.02). In univariable analysis, increasing age (1-unit change, OR 1.07 95% CI 1.02-1.129 p = 0.01) and severe disease (OR 9.95 95% CI 2.58-38.32 p =< 0.001) were associated with an increased risk of death. Male gender, non-Caucasian ethnicity, CLAD, CKD stage 3-5 were correlated with death with weak association. Conclusion(s): Recipient age is a significant risk factor for both hospitalisation and death, and older patients with COVID-19 should be monitored closely during COVID-19 illness. Molnupirivir is protective against hospitalisation, with Sotrovimab having a weak association. Further analysis of the protective effect of pre-exposure prophylaxis with emerging therapies such as Evusheld would be helpful to fully evaluate the currently available early disease therapies in Australia.

Real World Experience Using Tixagevimab/Cilgavimab (EvusheldTM) in Pre-Exposure Prophylaxis for Allogeneic Hematopoietic Cell Transplant Recipients: A Single Center Retrospective Review

Background: Tixagevimab(Txg)/cilgavimab (Cgv) was given emergency use authorization (EUA) to provide passive immunity against COVID-19(CoV) for immunocompromised (IC) pts who may not mount an adequate response to CoV vaccination [1]. Recipients of allogeneic hematopoietic cell transplant (Allo-HCT) are amongst the most IC. Due to high risk of mortality and complications of CoV in this population, Txg/ Cgv was used as pre-exposure prophylaxis (PrEP) under EUA without prior study. Our study aims to assess efficacy and adverse events (AE) of Txg/Cgv administration in this cohort of patients to help guide future practice. Method(s): We retrospectively investigated Allo-HCT recipients who received Txg/Cgv as PrEP. Data were gathered including changes in blood counts, incidence of graft-vs-host-disease (GVHD), history of prior CoV infection and vaccination status. Pts who developed CoV infection after PrEP were assessed for supplemental oxygen(O2) need and hospitalization. Data cutoff date was 9/30/2022. Result(s): A total of 18 Allo-HCT recipients received Txg/Cgv. Table 1 summarizes patient and transplant characteristics. Thirteen (72.2%) pts received 2 doses of 150mg of Txg / Cgv, while 4 pts received 1 dose of 300mg, and one patient received one dose of 150mg. Median time to first dose was 213 days [range 22-3660] post-transplant. Two pts had lab confirmed CoV, one at 24 days post dosing and the 2nd patient at 22 days post dose. Neither required supplemental O2;one was hospitalized for fever. Prior to dosing, 44.4% (8/18) of pts had GVHD. (Table Presented) (Figure Presented) (Figure Presented) Of these, 62.5% (5/8) had no changes in the severity of their GVHD. Two of 8 (25%) pts with pre-existing chronic GVHD had a flare of symptoms. Two (25%) had improvement of GVHD. Two pts developed new onset acute GVHD following Txg/Cgv administration, one requiring 1mg/kg prednisone and the other topical steroids (2/18, 11%). Figure 1 summarizes GVHD patterns observed. Hematologic parameters did not change significantly, see Figure 2. None of the pts reported any subjective AE following dosing. Summary: Txg/Cgv was found to be safe and effective for Allo-HCT pts, without significant toxicity. Two patients had new onset GVHD and 2 patients had progressive GVHD. Whether there is a true association between Txg/Cgv and development of GVHD should be investigated in a larger cohort and then investigated for possible underlying mechanisms.Copyright © 2023 American Society for Transplantation and Cellular Therapy

RETENTION IN CARE AMONG PERUVIAN MSM AND TGW IN A REAL-WORLD HIV PrEP PROGRAM

Background: Tenofovir-based daily oral HIV pre-exposure prophylaxis (HIV PrEP) is a highly efficacious HIV prevention modality, but sustained use over time is needed for continued protection among individuals at high risk for HIV exposure. Suboptimal adherence and retention in care threaten to diminish the impact of HIV PrEP on reducing HIV burden. PrEP PERU is an ongoing, multi-site, prospective cohort study evaluating HIV PrEP implementation among adult men who have sex with men (MSM) and transgender women (TGW) accessing care at non-government health centers in Peru. We sought to evaluate HIV PrEP adherence and retention in care among PrEP PERU participants prior to the onset of COVID-19 service disruptions. Method(s): We analyzed baseline and follow-up data from the PrEP PERU study through 3/15/2020, the first day of Peru's COVID-19 lockdown. MSM and TGW >=18 years of age with at least one HIV risk factor were eligible for enrollment. After the first follow-up visit at 4 weeks, TDF/FTC refills and clinic visits occur quarterly, at the discretion of the prescribing clinician. The medication is provided free of charge, but participants pay for laboratory testing plus a small service fee for clinic visits. Data is collected at baseline and quarterly follow-up visits on sexual risk behaviors and HIV PrEP use. We used bivariate analysis to evaluate the association between baseline factors and 6-month HIV PrEP retention in care. As a proxy for adherence, pharmacy dispensation records were used to calculate the proportion of days covered (PDC) by TDF/FTC. Result(s): Overall, 351 participants started TDF/FTC at four study sites in Lima from 1/23/2017 to 3/15/2020. Of this analysis population, 94% were cisgender men, 10% identified as bisexual, and median age was 31 (interquartile range [IQR], 27 - 38). Among those with at least 6 months of observation time (n=302), 91% attended >=1 follow-up visit and 77% attended >=2 follow-up visits during the 6 months after enrollment. The proportion with favorable adherence (PDC >=0.8) was 85%. There were 6 confirmed HIV seroconversions in the analysis period (1.2 per 100 person-years). Conclusion(s): In this analysis of HIV PrEP outcomes among MSM and TGW prior to COVID-19 pandemic disruptions in Peru, over 3/4 of the population remained in care and had favorable measures of adherence during the first 6 months after.

Changes in Service Access among People Who Inject Drugs in Philadelphia, 2018-2022

Background: The COVID-19 pandemic disrupted HIV prevention and treatment services, especially for structurally vulnerable individuals like many people who inject drugs (PWID). We sought to compare present levels of access to these services to their levels before the pandemic. Method(s): We used data from 2018 and 2022 collected through the National HIV Behavioral Surveillance (NHBS) survey among PWID in Philadelphia. Using generalized linear regression models, we estimated the associations between our exposure (year) and self-reported HIV testing, medical care, SSP access, PrEP use, and drug treatment in the year prior to interview. We calculated adjusted prevalence ratios (aPR) using multivariable models adjusted for age, race/ ethnicity, housing stability, and primary injecting drug. Result(s): There were 620 participants in 2018 and 604 in 2022 included in analyses. Compared to the 2018 sample, the 2022 sample was significantly older, non-Hispanic Black, and primarily injected drugs other than heroin. A significantly smaller proportion of participants in 2022 had a recent HIV test (57% vs. 71%), visited a health care provider (77% vs 82%), received sterile needles from an SSP (69% vs 75%), or participated in a drug treatment program (47% vs 54%). Between 2018 and 2022, PrEP awareness increased significantly (39% vs 54%) but PrEP use did not (3% vs 3%). In adjusted models, an 18% decrease in recent HIV testing was observed between 2018 and 2022 (aPR: 0.82;95% CI: 0.70-0.96). Among those who reported a recent HIV test, there was an 18% increase in testing in clinical settings observed between 2018 and 2022 (aPR: 1.18;95% CI: 1.10-1.26). Recent medical care, SSP access, PrEP use, and drug treatment were not associated with year in adjusted models. Conclusion(s): Access to a full range of social services is necessary for Ending the HIV Epidemic. These findings indicate that HIV prevention services, particularly HIV testing, among PWID have not rebound fully from the pandemic. Considering this and ongoing outbreaks of HIV among PWID, public health practitioners should closely monitor HIV testing frequency among PWID and prioritize expanding access to low-barrier HIV prevention and care services, especially in non-clinical settings.

Lymphocyte Trajectories and Outcomes of Covid-19 Infection in People with Hiv

Background: Studies have shown that lymphopenia and a decreased CD4/ CD8 ratio are correlated with the severity of COVID-19 infections. As people with HIV (PWH) can have altered CD4/CD8 ratios at baseline, this study examined the relationship between lymphocyte and T-cell subsets with COVID-19 disease outcomes among PWH. Method(s): This retrospective study included adult PWH (identified by HIV ICD codes, HIV RNA or antibody results, or antiretroviral therapy use excluding preexposure prophylaxis) in the Optum COVID-19 EHR database with positive SARSCoV- 2 PCR or antigen tests from February 2020 to December 2021. Outcomes included 30-day hospitalization, ICU stay, mechanical ventilation, and death from COVID-19. Absolute lymphocyte counts and percent and CD4:CD8 ratios were collected prior to SARS-CoV-2 positivity (baseline) and then weekly for four weeks post-SARS-CoV-2 positivity. We examined lymphocyte trajectories in PWH who had available data at all time points, and we compared changes in counts and percentages at each week post-SARS-CoV-2 to baseline values, using Wilcoxon rank sum test. Result(s): Of a total of 4,525 PWH who tested positive for SARS-CoV-2, 102 PWH had available lymphocyte counts at all study time points. Compared to non-hospitalized PWH (n=38), hospitalized PWH (n=64) and PWH who were in the ICU (n=32) or ventilator dependent (n=27) experienced a larger drop in lymphocyte percentage in the first two weeks post-SARS-CoV-2 diagnosis with only a partial recovery in subsequent weeks. In patients who died (n=19), lymphocyte percentage recovered even more slowly. Hospitalized PWH, as compared to non-hospitalized PWH, had a significant decrease in lymphocyte percentage post-SARS-CoV-2 infection in the first week (-0.19 vs -0.05;< 0.001), second week (-0.23 vs -0.02;< 0.001), third week (-0.20 vs 0.00;< 0.001), and fourth week (-0.10 vs 0.00;0.001), a trend seen in the ICU, mechanically ventilated, and deceased groups as well (Table 1). By the first week, CD4/CD8 ratio in COVID-19 positive patients was lower in the deceased (-0.18 vs 0.00;p=0.4), ventilator dependent (-0.15 vs 0.00;p=0.2), and ICU (-0.15 vs 0.00;p=0.4) groups. Conclusion(s): Our study showed that not only is lymphopenia a marker of COVID-19 disease severity in PWH but also a failure of lymphocyte percentage recovery is associated with worse outcomes. There was also a trend towards worse outcomes associated with a lower CD4/CD8 ratio in the first week after COVID-19 infection. (Figure Presented).

What Impact Will Worsening Air Pollution Have on the Burden of Covid-19?

Background: Evidence suggests association between long-term exposure to air pollutants and increased risk of becoming infected with SARS-CoV- 2, the causative agent of COVID-19, and increased severity of COVID-19. However, it remains unclear whether breathing more polluted air over many years affects susceptibility to infection or only affects disease severity, with uncertainty around the intensity of these associations. It has been estimated that anthropogenic emissions have contributed to over 10% of the over 660 million cases of SARS-CoV-2 and the over 7.5 million COVID-19 deaths reported worldwide over the course of the pandemic. Furthermore, as the world continues to warm and if air pollution levels increase, then so might the burden of respiratory infectious disease, including COVID-19. Method(s): Here we explore the potential impact of long-term exposure to increasing levels of particulate matter 2.5 microns or less in diameter (PM2.5) (+1 to +5 mug/m3) assuming an association on either (1) SARS-CoV-2 susceptibility or (2) COVID-19 disease severity by projecting SARS-CoV-2 infections and COVID-19-related hospital admissions over a two-year period. Simulations were conducted using a SARS-CoV-2 transmission model in a global setting capturing age and comorbidity risk, considering seasonality, emerging variants, and vaccination and treatment options. We model linear, log, and log10 relationships between these associations. Result(s): We show that if long-term exposure to higher levels of air pollution only affects COVID-19 severity, then as expected, the projected number of COVID-19-related hospitalisations would proportionally increase. However, if exposure directly affects the susceptibility of becoming infected, then while infections would be higher, hospitalizations would also be even higher due to the potential for onward transmission. This aligns with associations between air pollution and other respiratory infections and their associated health outcomes. Conclusion(s): The anticipated additional impact air pollution is having on the public health burden of respiratory infectious disease, like COVID-19, should be considered in strategic action plans to mitigate and adapt to changing levels of air pollution. It is important to better understand at which point air pollution affects SARS-CoV-2 infection acquisition through to disease progression, to enable improved protection and to better support those most vulnerable. Modelled impact of air pollution on COVID-19. The projected cumulative impact of long-term exposure to incrementally higher PM2.5 levels (+1 to +5 mug/m3) affecting either SARS-CoV-2 susceptibility or COVID-19 disease severity on cumulative SARS-CoV-2 infections and COVID-19-related hospital admissions over a two-year period in a global setting of 100,000 people. Age and comorbidity risk are captured, seasonality considered, and it is assumed SARS-CoV-2 variants of concern (with 10% more infectious and 20% more immune-evading than the previous variant, and Omicron-level severity) emerge every six months, and COVID-19 vaccination and treatment (monoclonalantibody PrEP and antivirals) are implemented for all those eligible. While the associations between PM2.5 exposure and either SARS-CoV-2 susceptibility or COVID-19 disease severity remains unclear and there is much uncertainty around estimated assumptions, here we show a modelled log10 relationship between these two potential associations. COVID-19: coronavirus disease 2019. PM2.5: particulate matter 2.5 microns or less in diameter. PrEP: pre-exposure prophylaxis. SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.