Investigation into the psychological impact of the COVID-19 pandemic for people living with HIV.

BACKGROUND: People living with HIV (PLWH) report high levels of anxiety. This study assessed the prevalence of COVID-19-related anxiety in PLWH. METHODS: Participants were recruited from two UK HIV clinics (01/03/2020 - 30/05/2022) and asked to complete the Coronavirus Anxiety Scale. The proportion with scores ≥9 (cut-off for dysfunctional pandemic-related anxiety) and ≥1 (reporting of any pandemic-related anxiety) were analysed. RESULTS: 115 PLWH were included, predominantly identifying as male (83.5%, n = 96), white (58.3%, n = 67) and reporting post-secondary education (82.6%, n = 95), with a median age of 51 years (range 22-93). Median CAS score was 0, with 4.4% scoring ≥9 (n = 5). More women scored ≥9 than men (16.7% (n = 3) and 2.1% (n = 2) respectively). Black African (13.6%, n = 3) and Other Ethnic Minority PLWH (25%, n = 2) had a greater proportion of scores ≥9 than White/Asian PLWH (both 0%). SARS-CoV-2 exposure was associated with scores greater than 1 but not greater than 9. CAS score was not associated with lower CD4 (<350 cells/mm3), detectable HIV viral load (≥50 copies/ml), or a history of pre-pandemic anxiety. CONCLUSIONS: Pandemic-related anxiety was low, but we identified a sub-population reporting dysfunctional pandemic related anxiety. Future work should further investigate the psychological impact of the pandemic on this group.

The British HIV Association national clinical audit 2021: Management of HIV and hepatitis C coinfection.

OBJECTIVES: We aimed to describe clinical policies for the management of people with HIV/hepatitis C virus (HCV) coinfection and to audit routine monitoring and assessment of people with HIV/HCV coinfection attending UK HIV care. METHODS: This was a clinic survey and retrospective case-note review. HIV clinics in the UK participated in the audit from May to July 2021 by completing an online questionnaire regarding their clinic's policies for the management of people with HIV/HCV coinfection, and by contributing to a case-note review of people living with HIV with detectable HCV RNA who were under the care of their service. RESULTS: Ninety-five clinics participated in the clinic survey; of these, 15 (15.8%) were regional specialist centres, 19 (20.0%) were HIV services with their own coinfection clinics, 40 (42.1%) were HIV services that referred coinfected individuals to a local hepatology service and 20 (21.1%) were HIV services that referred to a regional specialist centre. Eighty-one clinics provided full caseload estimates; of the approximately 3951 people with a history of HIV/HCV coinfection accessing their clinics, only 4.9% were believed to have detectable HCV RNA, 3.15% of whom were already receiving or approved for direct-acting antiviral (DAA) treatment. In total, 29 (30.5%) of the clinics reported an impact of COVID-19 on coinfection care, including delays or reductions in the frequency of services, monitoring, treatment initiation and appointments, and changes to the way that treatment was dispensed. Case-note reviews were provided for 283 people with detectable HCV RNA from 74 clinics (median age 42 years, 74.6% male, 56.2% HCV genotype 1, 22.3% HCV genotype 3). Overall, 56% had not received treatment for HCV, primarily due to lack of engagement in care (54.7%) and/or being uncontactable (16.4%). CONCLUSIONS: Our findings show that the small number of people with HIV with detectable HCV RNA in the UK should mean that it is possible to achieve HCV micro-elimination. However, more work is needed to improve engagement in care for those who are untreated for HCV.

Safety and Efficacy of the NVX-CoV2373 COVID-19 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial.

BACKGROUND: The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against COVID-19 in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover; data to the end of the placebo-controlled phase are reported. METHODS: Adults aged 18-84 years received two doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who seroconverted to immunoglobulin G (IgG) against the nucleocapsid protein and did not meet criteria for symptomatic COVID-19 were classified as having asymptomatic disease. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses. RESULTS: Of 15185 participants, 13989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5 months) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% CI: 73.3-88.8). Vaccine efficacy was 100% (17.9-100.0) against severe disease and 76.3% (57.4-86.8) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein-specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups. CONCLUSIONS: A two-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster dose may be indicated.

Attenuated humoral responses in HIV after SARS-CoV-2 vaccination linked to B cell defects and altered immune profiles.

We assessed a cohort of people living with human immunodeficiency virus (PLWH) (n = 110) and HIV negative controls (n = 64) after 1, 2 or 3 SARS-CoV-2 vaccine doses. At all timepoints, PLWH had significantly lower neutralizing antibody (nAb) titers than HIV-negative controls. We also observed a delayed development of neutralization in PLWH that was underpinned by a reduced frequency of spike-specific memory B cells (MBCs). Improved neutralization breadth was seen against the Omicron variant (BA.1) after the third vaccine dose in PLWH but lower nAb responses persisted and were associated with global MBC dysfunction. In contrast, SARS-CoV-2 vaccination induced robust T cell responses that cross-recognized variants in PLWH. Strikingly, individuals with low or absent neutralization had detectable functional T cell responses. These PLWH had reduced numbers of circulating T follicular helper cells and an enriched population of CXCR3+CD127+CD8+T cells after two doses of SARS-CoV-2 vaccination.

Assessing the impact of online postal self-sampling for sexually transmitted infections on health inequalities, access to care and clinical outcomes in the UK: protocol for ASSIST, a realist evaluation.

INTRODUCTION: The past decade has seen a rapid increase in the volume and proportion of testing for sexually transmitted infections that are accessed via online postal self-sampling services in the UK. ASSIST (Assessing the impact of online postal self-sampling for sexually transmitted infections on health inequalities, access to care and clinical outcomes in the UK) aims to assess the impact of these services on health inequalities, access to care, and clinical and economic outcomes, and to identify the factors that influence the implementation and sustainability of these services. METHODS AND ANALYSIS: ASSIST is a mixed-methods, realist evaluated, national study with an in-depth focus of three case study areas (Birmingham, London and Sheffield). An impact evaluation, economic evaluation and implementation evaluation will be conducted. Findings from these evaluations will be analysed together to develop programme theories that explain the outcomes. Data collection includes quantitative data (using national, clinic based and online datasets); qualitative interviews with service users, healthcare professionals and key stakeholders; contextual observations and documentary analysis. STATA 17 and NVivo will be used to conduct the quantitative and qualitative analysis, respectively. ETHICS AND DISSEMINATION: This study has been approved by South Central - Berkshire Research Ethics Committee (ref: 21/SC/0223). All quantitative data accessed and collected will be anonymous. Participants involved with qualitative interviews will be asked for informed consent, and data collected will be anonymised.Our dissemination strategy has been developed to access and engage key audiences in a timely manner and findings will be disseminated via the study website, social media, in peer-reviewed scientific journals, at research conferences, local meetings and seminars and at a concluding dissemination and networking event for stakeholders.

Safety, immunogenicity, and efficacy of a COVID-19 vaccine (NVX-CoV2373) co-administered with seasonal influenza vaccines: an exploratory substudy of a randomised, observer-blinded, placebo-controlled, phase 3 trial.

BACKGROUND: The safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines have not yet been reported. We therefore aimed to report the results of a substudy within a phase 3 UK trial, by evaluating the safety, immunogenicity, and efficacy of NVX-CoV2373 when co-administered with licensed seasonal influenza vaccines. METHODS: We did a planned exploratory substudy as part of the randomised, observer-blinded, placebo-controlled, phase 3 trial of the safety and efficacy of the COVID-19 vaccine (NVX-CoV2373) by co-administrating the influenza vaccine at four study hospitals in the UK. Approximately, the first 400 participants meeting the main study entry criteria-with no contraindications to influenza vaccination-were invited to join the substudy. Participants of the main study were randomly assigned (1:1) to receive two intramuscular injections of either NVX-CoV2373 (5 µg) or placebo (normal saline) 21 days apart; participants enrolled into the substudy were co-vaccinated with a single (0·5 mL) intramuscular, age-appropriate (quadrivalent influenza cell-based vaccine [Flucelvax Quadrivalent; Seqirus UK, Maidenhead] for those aged 18-64 years and adjuvanted trivalent influenza vaccine [Fluad; Seqirus UK, Maidenhead] for those ≥65 years), licensed, influenza vaccine on the opposite deltoid to that of the first study vaccine dose or placebo. The influenza vaccine was administered in an open-label manner and at the same time as the first study injection. Reactogenicity was evaluated via an electronic diary for 7 days after vaccination in addition to monitoring for unsolicited adverse events, medically attended adverse events, and serious adverse events. Immunogenicity was assessed with influenza haemagglutination inhibition and SARS-CoV-2 anti-spike protein IgG assays. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed in participants who were seronegative at baseline, received both doses of study vaccine or placebo, had no major protocol deviations affecting the primary endpoint, and had no confirmed cases of symptomatic COVID-19 from the first dose until 6 days after the second dose (per-protocol efficacy population). Immunogenicity was assessed in participants who received scheduled two doses of study vaccine, had a baseline sample and at least one post-vaccination sample, and had no major protocol violations before unmasking (per-protocol immunogenicity population). Reactogenicity was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo and had data collected for reactogenicity events. Safety was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo. Comparisons were made between participants of the substudy and the main study (who were not co-vaccinated for influenza). This study is registered with ClinicalTrials.gov, number NCT04583995. FINDINGS: Between Sept 28, 2020, and Nov 28, 2020, a total of 15 187 participants were randomised into the main phase 3 trial, of whom 15 139 received treatment (7569 received dose one of NVX-CoV2373 and 7570 received dose one of placebo). 431 participants were co-vaccinated with a seasonal influenza vaccine in the substudy (217 received NVX-CoV2373 plus the influenza vaccine and 214 received placebo plus the influenza vaccine). In general, the substudy participants were younger, more racially diverse, and had fewer comorbid conditions than those in the main study. Reactogenicity events were more common in the co-administration group than in the NVX-CoV2373 alone group: tenderness (113 [64·9%] of 174 vs 592 [53·3%] of 1111) or pain (69 [39·7%] vs 325 [29·3%]) at injection site, fatigue (48 [27·7%] vs 215 [19·4%]), and muscle pain (49 [28·3%] vs 237 [21·4%]). Incidences of unsolicited adverse events, treatment-related medically attended adverse events, and serious adverse events were low and balanced between the co-administration group and the NVX-CoV2373 alone group. No episodes of anaphylaxis or deaths were reported within the substudy. Co-administration resulted in no change to influenza vaccine immune response although a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. NVX-CoV2373 vaccine efficacy in the substudy (ie, participants aged 18 to <65 years) was 87·5% (95% CI -0·2 to 98·4) and in the main study was 89·8% (95% CI 79·7-95·5). INTERPRETATION: To our knowledge, this substudy is the first to show the safety, immunogenicity, and efficacy profile of a COVID-19 vaccine when co-administered with seasonal influenza vaccines. Our results suggest concomitant vaccination might be a viable immunisation strategy. FUNDING: Novavax.

Access to, usage and clinic outcomes of, online postal sexually transmitted infection services: a scoping review.

BACKGROUND: There has been considerable expansion in online postal self-sampling (OPSS) STI services in many parts of the UK, driven by increasing demand on sexual health services and developments in diagnostics and digital health provision. This shift in service delivery has occurred against a backdrop of reduced funding and service fragmentation and the impact is unknown. We explored characteristics of people accessing and using OPSS services for STIs in the UK, the acceptability of these services and their impact on sexual health inequalities. METHODS: A scoping review was conducted of studies published in English-language based on pre-agreed inclusion/exclusion criteria, between 01 January 2010 and 07 July 2021. Nine databases were searched, and 23 studies that met the eligibility criteria were included. Studies were appraised using the Mixed Methods Appraisal Tool. RESULTS: Study designs were heterogeneous, including quantitative, qualitative and mixed-methods analyses. The majority were either evaluating a single-site/self-sampling provider, exploratory or observational and of variable quality. Few studies collected comprehensive user demographic data. Individuals accessing OPSS tended to be asymptomatic, of white ethnicity, women, over 20 years and from less deprived areas. OPSS tended to increase overall STI testing demand and access, although return rates for blood samples were low, as was test positivity. There were varied results on whether services reduced time to treatment. OPSS services were acceptable to the majority of users. Qualitative studies showed the importance of trust, confidentiality, discretion, reliability, convenience and improved patient choice. CONCLUSION: OPSS services appear highly acceptable to users. However, uptake appears to be socially patterned and some groups who bear a disproportionate burden of poor sexual health in the UK are under-represented among users. Current provision of online self-sampling could widen health inequalities, particularly where other options for testing are limited. Work is needed to fully evaluate the impact and cost-effectiveness of OPSS services.

Measuring and evaluating sexual health in the era of digital health: challenges and opportunities.

Digital health has become increasingly embedded within sexual health service delivery and is now an established part of the user journey. It can support the provision of information and access to care across the sexual health continuum and facilitate the delivery of differentiated care with tailored and layered interventions that meet an individual's and target populations' need. However, despite advances in digital health, many challenges remain in the measurement and evaluation of sexual health. Reaching underserved populations, ensuring that both the intervention and the outcomes being measured are appropriate, and consistent collection of data (across settings and over time) are all potential obstacles to a full realisation of these opportunities. In order for digital health to improve sexual health and wellbeing, and reduce morbidity, the following need to occur: (1) ensure the necessary digital, health care, laboratory, legal and regulatory and surveillance infrastructure is in place to provide access to those with a sexual health need; (2) empowerment of end users and communities to take control of their own health through engagement in the development of interventions, and to ensure that outcomes of importance are measured; (3) tailoring and layering of interventions to provide equitable access to care; (4) integrating the digital ecosystem with the existing healthcare and external ecosystem; (5) measure and evaluate the unmet needs, gaps and quality of the experience, taking a realist evaluation approach; and (6) measure and evaluate the economic and distributional impacts associated with digital services or interventions in sexual health.

Ethnic inequalities in mental health and socioeconomic status among older women living with HIV: results from the PRIME Study.

OBJECTIVES: Women living with HIV in the UK are an ethnically diverse group with significant psychosocial challenges. Increasing numbers are reaching older age. We describe psychological and socioeconomic factors among women with HIV in England aged 45-60 and explore associations with ethnicity. METHODS: Analysis of cross-sectional data on 724 women recruited to the PRIME Study. Psychological symptoms were measured using the Patient Health Questionnaire 4 and social isolation with a modified Duke-UNC Functional Social Support Scale. RESULTS: Black African (BA) women were more likely than Black Caribbean or White British (WB) women to have a university education (48.3%, 27.0%, 25.7%, respectively, p<0.001), but were not more likely to be employed (68.4%, 61.4%, 65.2%, p=0.56) and were less likely to have enough money to meet their basic needs (56.4%, 63.0%, 82.9%, p<0.001). BA women were less likely to report being diagnosed with depression than WB women (adjusted odds ratio (aOR) 0.40, p<0.001) but more likely to report current psychological distress (aOR 3.34, p<0.05). CONCLUSIONS: We report high levels of poverty, psychological distress and social isolation in this ethnically diverse group of midlife women with HIV, especially among those who were BA. Despite being more likely to experience psychological distress, BA women were less likely to have been diagnosed with depression suggesting a possible inequity in access to mental health services. Holistic HIV care requires awareness of the psychosocial needs of older women living with HIV, which may be more pronounced in racially minoritised communities, and prompt referral for support including psychology, peer support and advice about benefits.

Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV.

There is an urgent need to understand the nature of immune responses against SARS-CoV-2, to inform risk-mitigation strategies for people living with HIV (PLWH). Here we show that the majority of PLWH with ART suppressed HIV viral load, mount a detectable adaptive immune response to SARS-CoV-2. Humoral and SARS-CoV-2-specific T cell responses are comparable between HIV-positive and negative subjects and persist 5-7 months following predominately mild COVID-19 disease. T cell responses against Spike, Membrane and Nucleoprotein are the most prominent, with SARS-CoV-2-specific CD4 T cells outnumbering CD8 T cells. We further show that the overall magnitude of SARS-CoV-2-specific T cell responses relates to the size of the naive CD4 T cell pool and the CD4:CD8 ratio in PLWH. These findings suggest that inadequate immune reconstitution on ART, could hinder immune responses to SARS-CoV-2 with implications for the individual management and vaccine effectiveness in PLWH.

Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine.

BACKGROUND: Early clinical data from studies of the NVX-CoV2373 vaccine (Novavax), a recombinant nanoparticle vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that contains the full-length spike glycoprotein of the prototype strain plus Matrix-M adjuvant, showed that the vaccine was safe and associated with a robust immune response in healthy adult participants. Additional data were needed regarding the efficacy, immunogenicity, and safety of this vaccine in a larger population. METHODS: In this phase 3, randomized, observer-blinded, placebo-controlled trial conducted at 33 sites in the United Kingdom, we assigned adults between the ages of 18 and 84 years in a 1:1 ratio to receive two intramuscular 5-µg doses of NVX-CoV2373 or placebo administered 21 days apart. The primary efficacy end point was virologically confirmed mild, moderate, or severe SARS-CoV-2 infection with an onset at least 7 days after the second injection in participants who were serologically negative at baseline. RESULTS: A total of 15,187 participants underwent randomization, and 14,039 were included in the per-protocol efficacy population. Of the participants, 27.9% were 65 years of age or older, and 44.6% had coexisting illnesses. Infections were reported in 10 participants in the vaccine group and in 96 in the placebo group, with a symptom onset of at least 7 days after the second injection, for a vaccine efficacy of 89.7% (95% confidence interval [CI], 80.2 to 94.6). No hospitalizations or deaths were reported among the 10 cases in the vaccine group. Five cases of severe infection were reported, all of which were in the placebo group. A post hoc analysis showed an efficacy of 86.3% (95% CI, 71.3 to 93.5) against the B.1.1.7 (or alpha) variant and 96.4% (95% CI, 73.8 to 99.5) against non-B.1.1.7 variants. Reactogenicity was generally mild and transient. The incidence of serious adverse events was low and similar in the two groups. CONCLUSIONS: A two-dose regimen of the NVX-CoV2373 vaccine administered to adult participants conferred 89.7% protection against SARS-CoV-2 infection and showed high efficacy against the B.1.1.7 variant. (Funded by Novavax; EudraCT number, 2020-004123-16.).

Descriptive account of 18 adults with known HIV infection hospitalised with SARS-CoV-2 infection.

OBJECTIVE: To report on the clinical characteristics and outcome of 18 people living with HIV (PLWH) hospitalised with SARS-CoV-2 infection in a London teaching hospital. METHODS: The hospital notes of 18 PLWH hospitalised with SARS-CoV-2 infection were retrospectively reviewed alongside data concerning their HIV demographics from an established HIV Database. RESULTS: The majority (16/18) had positive PCR swabs for SARS-CoV-2, and two had negative swabs but typical COVID-19 imaging and history. Most were male (14/18, 78%), median age 63 years (range 47-77 years). Two-thirds were migrants, nine (50%) of Black, Asian and minority ethnicity (BAME). All were diagnosed with HIV for many years (range 8-31 years), and all had an undetectable HIV viral load (<40 copies/mL). The median CD4 prior to admission was 439 (IQR 239-651), and 10/16 (63%) had a CD4 nadir below 200 cells/mm3. Almost all (17/18) had been diagnosed with at least one comorbidity associated with SARS-CoV-2 prior to admission. 3/18 patients died. None received mechanical ventilation. Hospital stay and clinical course did not appear prolonged (median 9 days). CONCLUSIONS: Our data suggest that PLWH may not necessarily have prolonged or complex admissions to hospital when compared with the general hospital and national population admitted with COVID-19. Many had low nadir CD4 counts and potentially impaired functional immune restoration. The PLWH group was younger than generally reported for COVID-19, and the majority were male with multiple complex comorbidities. These patients had frequent contact with hospital settings increasing potential for nosocomial acquisition and increased risk of severe COVID-19.