Successful ECMO course in an Acquired Immune Deficiency Syndrome (AIDS) patient with ARDS complicated by pneumocystis jirovecii pneumonia and COVID-19: A unique case

Objectives: Reviewing current literature and case reports of patients placed on Venous-Venous ECMO support for HIV and AIDS, with confection with Pneumocystis pneumonia and covid-19 pneumonia. The use of extracorporeal membrane oxygenation (ECMO) in patients who have acute respiratory distress syndrome has been shown to have very good outcomes. However, there is limited data to support the initiation of ECMO in patients who have human immunodeficiency virus infection with or without acquired immune deficiency syndrome. Method(s): We present a unique and challenging case of a 30 year old male, with no known past medical history, unvaccinated against covid-19, who presented with one week of progressive shortness of breath. On admission he was found with moderate bilateral infiltrates and was diagnosed with covid-19 pneumonia. Despite appropriate medical therapy, patient developed worsening hypoxic respiratory failure. Found to have elevated (1- 3)-7beta;-d-glucan and tested positive for HIV. CD4 count 11, HIV viral load 70,000. The patient remained severely hypoxemic despite mechanical ventilation, sedation, paralytics and proning. Venous venous extracorporeal membrane oxygenation was initiated. Considering his non improvement with variety of antivirals and antibiotics and with elevated (1-3)-7beta;-d-glucan in the setting of AIDS he was treated for presumed Pneumocystis pneumonia. The patient tolerated proning while on VV ECMO and his course was complicated with bilateral pneumothorax necessitating chest tube placement. Result(s): The patient successfully completed 64 days on VV ECMO, where he was treated for PCP pneumonia, covid pneumonia, CMV viremia and tolerated initiation of anti-retroviral therapy. Patient was successfully decannulated, and ultimately discharged from the hospital. Conclusion(s): VV-ECMO can be a beneficial intervention with successful outcomes in severely immunocomprimised patients with AIDS. This case highlights the importance of minimizing sedation and early mobilization on ECMO support. (Figure Presented).

A critical review of public–private partnerships in the COVID-19 pandemic: key themes and future research agenda

PurposeUndoubtedly, coronavirus (COVID-19) pandemic has released unprecedented disruptions and health crisis on people and activities everywhere. The impacts extend to public–private partnership (PPP) arrangements in the construction industry. Concomitantly, PPP pacts are contributing to combat the pandemic. However, literature on the PPP concept in the COVID-19 era remain under-researched. This study aims to review the current literature on PPPs in the COVID-19 pandemic and present the key themes, research gaps and future research directions.Design/methodology/approachIn this study, 29 highly relevant literature were sourced from Web of Science, Scopus and PubMed search engines within the systematic literature review (SLR) methodology. With the aid of qualitative content analysis, the 29 articles were critically analysed leading to the extraction of hot research themes on PPPs in the coronavirus pandemic.FindingsThe results of the SLR produced eight themes such as major changes in PPP contracts, development of the COVID-19 vaccines, economic recession, facemasks and testing kits, governance and sustainability of PPPs. In addition, the study reveals seven research gaps that need further investigations among the scientific research community on mental health and post-pandemic recovery plans.Research limitations/implicationsThe articles selected for this review were limited to only peer-reviewed journal papers written in English excluding conference papers. This restriction may have taken out some relevant literature but they had insignificant impact on the overall outcome of this research.Practical implicationsTo improve the understanding of practitioners in the construction industry on key issues on PPPs in the COVID-19 pandemic, the study provides them a checklist of relevant themes.Originality/valueAs a novel literature review relating PPPs to the coronavirus, it sets the foundation for further research and contributes to practical measures to control the virus.

Tuberculosis and Hiv Infection - So Many Questions Pending

Since the early days of HIV infection, back in the eighties, TB - particularly extrapulmonary TB emerged as one of the opportunistic infections affecting these patients, specifically as a reactivation of latent TB infections. A diagnosis of TB in the context of HIV infection was then considered as an 'AIDS defining condition' according to classification systems used at that time. It has been recognized for a long time that there are many interactions between HIV and Mycobacterium tuberculosis, which lead to further immune deterioration and to worsening of both conditions due to complex biological and mechanistic interactions between these two agents. Many methods and techniques have been proposed in order to improve diagnosis of TB in HIV-infected subjects, knowing that TB is the most frequent opportunistic infection;and, if not treated in a timely fashion, it may easily take the lives of affected patients. It is not easy to have a diagnosis of TB in HIV-infected subjects, because of the difficulties for obtaining adequate sputum samples, or because of lack of adequate facilities for making a timely diagnosis, particularly in the so-called developing world. On the other hand, extrapulmonary TB is most frequently found in HIV-infected individuals compared to non-infected subjects, and its diagnosis poses significant difficulties, since so many times invasive procedures must be performed in order to obtain an adequate tissue sample and then be able to identify the pathological characteristics of tuberculous disease. In the first days of HIV infection when no antiretroviral therapy was available, a diagnosis of TB was made on clinical grounds, considering a history of contact or some characteristics of the disease, and those of us who are old (or experienced) enough offered antituberculosis therapy for these subjects, obtaining an adequate response many times, but in all cases, the natural history of HIV infection took place, and ultimately these patients died because of the occurrence of another opportunistic infection (or malignancy). With the advent of antiretroviral therapy in the late nineties, another problem occurred. The possibility of drug-drug interactions, taking into account hepatic metabolism of rifampin and the alterations of antiretroviral drug blood - or tissue - concentrations. On top of this, the occurrence of IRIS became another problem, and strategies and protocols have been designed in order to establish the adequate timing of antituberculosis therapy and sometime later antiretroviral therapy. A last point to be considered is the COVID-19 pandemic. The question to be asked is what the influence of the pandemic has been for affecting TB and HIV diagnosis and therapy strategies and programs, particularly in the developing world, knowing that health systems in these countries have many limitations, and that - scant - resources had to be dedicated for the fight against the pandemic.Copyright © 2023

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.

COVID-19 vaccination rates in people living with HIV in north east England

Background: People living with HIV (PLWH) are at increased risk of severe COVID-19. The UK recommends vaccination against COVID-19 for PLWH with two primary doses, a booster dose, then seasonal boosters (i.e. four doses by Autumn 2022). Vaccination uptake in the UK has been lower among non-white minority ethnic groups than in the white British population, despite these groups having a higher risk of severe COVID-19. Method(s): We evaluated vaccine uptake by PLWH attending treatment services at two NHS Trusts in North East England. To ensure representation of minorities, alternating PLWH from white and ethnic minorities (excluding white minorities) were purposively selected for review from the HIV and AIDS Reporting System;vaccination data were obtained from regional integrated care records. Result(s): 200 PLWH were included. 103 (51.5%) were from ethnic minority groups, of whom 78 (75.7%) were of black African ethnicity. Vaccination rates in the total population and among ethnic groups are shown in the table below. Similar proportions of white and minority ethnic background PLWH had received up to two vaccinations. These proportions among white PLWH were similar to those reported in the general English population, while fewer Black African PLWH were unvaccinated than in the general population (14.1% vs. 26%, data not shown). Vaccine uptake among PLWH diverged beyond 3 doses, with white people being almost three times as likely to have received four doses (OR 2.92;95% CI 1.63 to 5.19;pvalue for difference in distribution across all doses=0.005). Conclusion(s): Although ethnic minority PLWH were less likely to be fully vaccinated than white ethnicity PLWH, the proportion of unvaccinated black African PLWH was lower than that reported from the general population. This could infer that regular contact with healthcare professionals coupled with consistent promotion of vaccination by HIV clinicians can improve uptake. (Table Presented).

Comorbidities in people living with HIV in the north east who are unvaccinated against COVID-19: a descriptive study

Background: People living with HIV (PLWH) are at increased risk of severe or critical COVID-19. This is in addition to the increased risk associated with any coexisting conditions such as chronic pulmonary disease (CPD), chronic kidney disease and cardiovascular disease. Vaccination against COVID-19 is therefore strongly recommended for PLWH. Method(s): We conducted a descriptive study to evaluate comorbidities among PLWH attending for HIV care at two NHS Trusts in North East England and who were under- or unvaccinated against COVID-19, defined as having received either zero or 1 doses of any COVID-19 vaccine by 01/10/2022. PLWH under active care were identified using the HIV and AIDS Reporting System (HARS) dataset. Vaccination data were obtained from regional integrated care records (RICR) and cross-referenced with HARS. Information on comorbidities was collated for any patients who were under- or unvaccinated. To quantify risk and clinical vulnerability, we calculated the Charlson Comorbidity Index (CCI) for each of these patients. A CCI score >=1 is associated with mortality/poor outcomes in patients with COVID-19. Result(s): 141 under- or unvaccinated patients were identified out of a total cohort of 1492 patients who attended for HIV care (9.5%);of these, 96 (68.1%) and 45 (31.9%) had received zero and one vaccination respectively. The median age of this under-/unvaccinated cohort was 41 years and 91 (64.5%) were male. 62 patients (44.0%) had a CCI score of 1 or more;13 patients (9.2%) had a diagnosis of AIDS during the time period evaluated;11 (84.6%) of the patients with an AIDS diagnosis were completely unvaccinated. Non-HIV comorbidities included liver disease (10/141, 7.1%), solid organ cancer (5/141, 3.5%), CPD (4/141, 2.8%) and connective tissue disease (3/141, 2.1%). Six patients (4.3%) had >=2 comorbidities. Conclusion(s): Nearly half of the under-/unvaccinated PLWH attending our services were identified as being at an increased risk of having a poor outcome in the event of contracting COVID-19. Proactively identifying these individuals would allow services to offer tailored support in making informed decisions about vaccinations. Useful strategies may include the use of patient information leaflets and targeted discussion with patients explaining their individual risk from COVID-19.

Clinical epidemiology of COVID-19 in Black people with HIV in south London, UK

Background: The COVID-19 pandemic disproportionally affected Black communities who were at greater risk of SARS-CoV-2 acquisition, morbidity, and mortality than those of White ethnicity. We describe the clinical epidemiology of COVID-19 in the GEN-AFRICA cohort of Black people with HIV in two South London clinics. Method(s): First reported episodes of COVID-19 up to 12/2021 were ascertained by direct questioning and/or medical records review. The cumulative incidence of COVID-19 and vaccination was determined by Nelson- Aalen methods. Pre-pandemic immunovirological and comorbidity status obtained prior to 01/2020 was used to identify risk factors for COVID-19 using Cox regression. We compared characteristics of participants with mild/ moderate (not requiring hospitalization) and severe (requiring hospitalization or resulting in death) COVID-19. Result(s): COVID-19 status was available for 1184 (95%) of 1289 GEN-AFRICA participants (mean age 49.1 years;55% female;median CD4 565;93% HIV RNA <200), and SARS-CoV-2 vaccination status for 1160;998 (86%) had received at least one vaccine dose (administered to 50% by 16/02/2021). A total of 310 participants (26.2%) reported a first episode of COVID-19 (any severity), with a cumulative incidence of 6%, 14%, 15% and 22% following the initial, alpha, delta, and omicron waves. Women, people of East African ancestry, and those with detectable HIV RNA were more likely to report COVID-19 (Table). CD4 (current/nadir), class of antiretroviral therapy (ART), and comorbidity status were not associated with COVID-19. Findings were similar when restricted to episodes in 2020 (prior to vaccine availability) or testconfirmed COVID-19. Severe COVID-19 cases (N=34) were more often male (p=0.002), of West-African ancestry (p=0.01), with lower CD4 cell counts (p=0.002), and they more often had a history of AIDS, diabetes mellitus, cardiovascular disease, and chronic kidney disease (all p=0.001) compared to mild/moderate cases;they were also more likely to be on protease inhibitor (PI)- containing ART (p=0.01). Conclusion(s): By the end of the second year of the pandemic, 22% of black people with HIV in South London had experienced COVID-19. Immune and comorbidity status were not associated with COVID-19 when all cases were considered but strongly associated with severe COVID-19 disease, as were West-African ancestry and being on a PI. (Table Presented).

Some STIs spike, but the declines are just as concerning

Decreasing cases of chlamydia may offer false hope in light of decreased screening "Stay home, save lives" and social distancing have been common tag-lines over the last 2 years, but some public health experts are adding "We're back to the 80s" to the mix, specifically in terms of rising cases of sexually transmitted infections (STI) to levels not seen in decades. Social distancing may have helped by limiting sexual activity and exposure to new partners, but it may also have resulted in delayed care for many people, according to CDC.3 There is also a suspicion that better treatment of HIV/AIDs has led to a more laissez-faire attitude about STIs in general. Since the virus no longer carries a death sentence for many, the u-shaped curve that cases of STIs have shown in the last few decades reflects a potential drop in concern. "Chlamydia dropped because it is only caught through screening, but we know that pelvic inflammatory disease and infertility have also dropped since large-scale chlamydia screening started up again.

Granulomatous Hepatitis as Primary Manifestation of Disseminated Histoplasmosis in an Immunocompetent Host Diagnosed on EUS FNA and Liver Biopsy

Introduction: Disseminated histoplasmosis (DH) presents as primarily lung manifestations with extrapulmonary involvement in immunocompromised hosts. Granulomatous hepatitis as first presentation of DH in an immunocompetent host is uncommon. Case Description/Methods: 25-year-old female presented with one month of fever, fatigue, myalgias, 30-pound weight loss, cough, nausea, vomiting, and epigastric pain. She has lived in the Midwest and southwestern US. Presenting labs: TB 1.9 mg/dL, AP 161 U/L, AST 172 U/L, ALT 463 U/L. Workup was negative for COVID, viral/autoimmune hepatitis, sarcoidosis, tuberculosis, and HIV. CT scan showed suspected gallstones and 9 mm left lower lobe noncalcified nodule. EUS showed a normal common bile duct, gallbladder sludge and enlarged porta hepatis lymph nodes which underwent fine needle aspiration (FNA). She was diagnosed with biliary colic and underwent cholecystectomy, with white plaques noted on the liver surface (A). Liver biopsy/FNA showed necrotizing granulomas (B) and fungal yeast on GMS stain (C). Although histoplasmosis urine and blood antigens were negative, histoplasmosis complement fixation was >1:256. She could not tolerate itraconazole for DH, requiring amphotericin B. She then transitioned to voriconazole, discontinued after 5 weeks due to increasing AP. However, her symptoms resolved with normal transaminases. At one year follow up, she is asymptomatic with normal liver function tests. Discussion(s): DH is a systemic granulomatous disease caused by Histoplasma capsulatum endemic to Ohio, Mississippi River Valley, and southeastern US. DH more commonly affects immunocompromised hosts with AIDS, immunosuppressants, and organ transplant. Gastrointestinal involvement is common in DH (70-90%) with liver involvement in 90%. However, granulomatous hepatitis as primary manifestation of DH is rare (4% of liver biopsies). Hepatic granulomas are seen in < 20%. Patients may present with nonspecific systemic symptoms. Serum/urine antigens may be negative. Gold standard for diagnosis is identifying yeast on tissue stains. Recommended treatment is amphotericin B followed by 1 year of itraconazole. However, shorter treatment duration may be effective in immunocompetent hosts. This case is unique in that granulomatous hepatitis was the first presentation of DH in our immunocompetent patient diagnosed on EUS FNA and liver biopsy. Clinicians must have a high degree of suspicion for DH in patients with fever of unknown origin especially in endemic areas regardless of immunologic status. (Table Presented).

Mortality among people with HIV in the UK in 2021: findings from the National HIV Mortality Review

Background: The National HIV Mortality Review (NHMR) was launched by UK Health Security Agency (UKHSA) and British HIV Association to better recognise causes of death and preventable death, and to describe end-of-life care, among people with HIV. Method(s): UK HIV services submitted data on all known deaths among people with HIV under their care in 2021 through a secure online form. Cause of death was categorised by an epidemiologist and four clinicians using the Coding Causes of Death in HIV protocol. Result(s): In 2021, 101 services reported 606 deaths among people with HIV to NHMR. In 2019, 74 services reported to the NHMR while 121 reported in 2020. Median age at death was 58 [interquartile range (IQR): 56-59] and most (76%) were male. Death cause was ascertainable for 78% (n=475), with the most common being non-AIDS-related cancers (26%), followed by non-AIDS-defining infections (19%), cardiovascular disease (16%), AIDS (9%), substance misuse (8%), respiratory disease (4%), accident/suicide (3%), liver disease (2%) and other causes (11%). COVID- 19 caused or contributed to 11% of all deaths. Thirtythree people (5%) died within a year of HIV diagnosis, 90% of these were diagnosed late (CD4<350 cells/mm3), 80% very late (CD4<200 cells/mm3), 54% diagnosed with AIDS and 33% had documented missed opportunities for earlier diagnosis. Viral suppression (<200 copies/mL) (87%) and treatment coverage (98%) was high with the median time on treatment 13 years [IQR: 8-20]. Common lifestyle risk factors in the preceding year included smoking (33%;n=179), excessive alcohol use (20%;n=103). Other factors included drug use (non-injecting and injecting) and opioid substitution therapy. Death had been expected for 298 (49%) individuals, of whom 230 had discussed end-of-life care and 108 had a documented advanced end-of-life care plan in place. Conclusion(s): Over half of people living with diagnosed HIV are aged over 50. Most deaths were not AIDS related however, one in eleven people with diagnosed HIV in the UK died from AIDS. Of people that died within a year of diagnosis, one in three had documented missed opportunities for earlier HIV diagnosis.

Neutralising antibodies (NAbs) against SARS-CoV-2 in BNT162b2 vaccine recipients with a history of advanced HIV infection: cPass as a simpler alternative to gold-standard tests

Background: Established SARS-CoV-2 NAb tests are labor-intensive. We prospectively measured NAbs vs Wuhan-1 and Omicron BA.2 using the novel GenScript cPass assay and examined correlations with responses measured by gold-standard plaque reduction neutralisation test (PRNT) (Cotugno, Ruggiero et al. Cell Rep 2021) and with anti-Spike IgG quantified by Roche Elecsys. Given the paucity of data, we selected BNT162b2 vaccine recipients with a history of advanced HIV infection (prior AIDS-defining conditions and/or nadir CD4 <200 cells). Method(s): In Mar 2021-Apr 2022, 55 PWH received 2 vaccine doses median 3 weeks apart [IQR 3-3] and a 3rd dose 27 weeks later [23-31]. Plasma samples (n=147) were stored immediately before dose-1 (T0), median 4 weeks [3-5] after dose-2 (T1) and median 13 weeks [9-19] after dose-3 (T2) for batch testing. Result(s): Participants' characteristics: 74% male, 85% white, all on ART, 82% HIV-RNA <50 cps/ml;median age 55 years, ART duration 7 years, nadir CD4 83 cells [36-211], current CD4 440 cells [270-710], CD4:CD8 ratio 0.6 [0.4-1.0];73% had a history of advanced HIV infection;15% received a COVID-19 diagnosis during the study. At T0, T1 and T2, proportions with quantifiable anti-S IgG (>0.8 U/ml) were 11/49 (22%), 50/54 (93%) and 43/43 (100%), respectively;their median anti-S IgG titres were 30 [15-124], 15949 [596-3389] and 8527 [3146-17190] U/ml. Proportions showing Wuhan-1 neutralisation by cPass were 6/50 (12%), 45/53 (85%) and 40/43 (93%), with median neutralisations of 67% [47-70], 97% [91-98] and 98% [98-98] and corresponding NAb titres of 1332 [792-1436], 5354 [3529-6187] and 6242 [5765-6766] U/ml. At T2, 25/28 (89%) showed BA.2 neutralisation by cPass (median 83% [68-93];NAb titre 7836 [3172-12173] U/ml) (Fig 1A). Two participants lacking NAbs at T2 had a history of advanced HIV infection. cPass data were highly correlated with anti-S IgG titres (rho 0.82;p<0.0001) and with PRNT data for both Wuhan-1 (n=27, Fig 1B) and Omicron BA.2 (n=28, Fig 1C). Conclusion(s): cPAss offers a simple methodology for measuring SARS-CoV-2 NAbs. Despite prior advanced HIV infection, neutralising activity improved with successive vaccinations and most participants showed NAbs against both Wuhan-1 and Omicron BA.2 after 3 vaccine doses. (Figure Presented).

The impact of the COVID-19 pandemic on cervical screening and outcomes for women living with HIV

Background: Current published Faculty of Sexual and Reproductive Health (FSRH) guidelines recommend annual cervical screening for women living with HIV(WLHIV) but do not reflect current evidence. Aim(s): 1. To assess the impact of the Covid-19 pandemic on frequency and interval of cervical screening in WLHIV 2. To report any changes in outcomes of cervical screening in WLHIV during Covid-19 Method: Data were collected retrospectively over 3 years defined as Pre-Covid (23/3/2019-22/3/2020), during Covid lockdowns (23/3/2020-22/3/2021) and Post-Covid lockdowns (23/3/2021-22/3/2022). Data was collated on demographics, HIV-related data, previous abnormal cervical screens/colposcopy, smoking and high-risk Human Papilloma Virus(hrHPV) vaccination. Result(s): Data was available for 70 women. Mean age was 48 years, 44.3%(n=31) were of African ethnicity. Mean duration of HIV diagnosis was 19 years. 22.9% (n=16) had a previous ADI, median CD4 was 768(range 35-1891), median nadir-CD4 439(range 3-1472), 94.3% (n=66) were taking ARVs and 87.1%(n=61) had HIV-VL <40 copies/ml. 42.9%(n=30) had a previous abnormal cervical screen and 78.6%(n=55) had undergone colposcopy. 4.3%(n=3) were vaccinated against hrHPV. 18.6% (n=13) currently smoked. 60%(n=42) women underwent cervical screening Pre- Covid, 41.4%(n=29) during and 78.6%(n=55) Post-Covid. 19.6-37.2% fewer women were screened during Covid compared to Pre and Post-Covid. 9.5%(n=4) women screened Pre-Covid tested positive for hrHPV compared with 6.9%(n=2) during Covid and 12.7%(n=7) Post-Covid. No cytology changes were seen for the majority however cervical intraepithelial neoplasia(CIN) grade 1 was detected in 2.4%(n=1) Pre- Covid, compared with 3.4%(n=1) during covid and 5.4% (n=3) Post-covid. Post-Covid 1.82%(n=1) had CIN grade 2 detected, no women pre or during covid had CIN grade 2 detected. No women Pre, during or Post-covid had CIN grade 3 or cervical neoplasm detected on cytology. Conclusion(s): Covid increased cervical screening intervals for WLHIV but did not result in delayed cervical cancer diagnosis. FSRH guidelines are currently under review regarding screening intervals. This data, although small in number, may support European AIDS Clinical Society and Department of Health and Human Services guidelines which have extended screening intervals for PWLH especially for those who tested negative for hrHPV.

Factors associated with severe SARSCOV- 2 infection in people of Black ethnicities living with HIV in the UK

Background: The COVID-19 pandemic has disproportionally affected people of black ethnicities, who have been at greater risk of SARS-CoV-2 acquisition, morbidity and mortality than those of white ethnicity. We describe factors associated with severe COVID-19 infection in the GEN-AFRICA cohort of people of black ethnicities living with HIV in the U.K. Method(s): First reported episodes of COVID-19 up to October 2022 were ascertained by direct questioning and/or medical records review. Pre-pandemic immune-virological and comorbidity status was based on measurements obtained prior to 01/2020 and used to identify risk factors for severe (requiring hospitalisation or resulting in death) COVID-19, using logistic regression Results: COVID-19 status was available for 1806 (72%) of 2503 GEN-AFRICA participants (mean age 49.2 [SD 10.2] years;56% female;80% sub-Saharan African and 14% Caribbean ancestry, median CD4 count 555 [IQR 400-733] cells/mm3;93% undetectable HIV RNA [<200 copies/ mL]);573 (32%) reported a clinical illness consistent with COVID-19;63 (3.5%) experienced severe COVID-19 (hospitalisation 59;death 4). Those who experienced severe COVID-19 were older, more often male, had lower CD4 counts and fewer had undetectable HIV RNA;they more often had prior AIDS, hypertension, diabetes mellitus and chronic kidney disease. Region of ancestry, nadir CD4 count, and obesity were not associated with severe COVID-19. In multivariable analysis, CD4 count <350 cells/mm3, diabetes mellitus and chronic kidney disease were associated with increased odds of severe COVID-19 (Table). Sex and a pre-pandemic HIV RNA were associated with severe disease although this did not reach statistical significance. By October 2022, 1534 (88%) of this sample had received >=1 dose of SARS-CoV-2 vaccine;those who experienced severe COVID-19 were less likely to report vaccination (77% vs. 89%, p=0.01). Conclusion(s): By the end of October 2022, nearly onethird of people of Black ethnicities with HIV in this sample had experienced COVID-19;3.5% had developed severe COVID-19 disease. Pre-pandemic immunovirological and comorbidity status were associated with severe COVID-19. Black populations with less favourable HIV control than observed for GEN-AFRICA participants may have suffered greater COVID-19 morbidity and mortality. (Table Presented).

Multilocular thymic cyst detected during COVID­19 treatment in an HIV­positive adult man: A case report and literature review.

A multilocular thymic cyst (MTC) is a rare mediastinal tumor with multiloculated cyst-like structures in the anterior mediastinum. This tumfor is associated with inflammatory diseases, including human immunodeficiency virus (HIV) infection. The present study reports a case of MTC detected during coronavirus disease 2019 (COVID-19) treatment in an adult who was tested HIV positive. An anterior mediastinal tumor was incidentally detected on computed tomography in a 52-year-old man with a 20-year history of HIV infection on the 9th day of COVID-19. The patient was asymptomatic with no notable physical findings. Magnetic resonance imaging revealed a 28-mm bilocular cyst. Robot-assisted thoracoscopic tumor resection was performed. Pathological examination showed that the cyst was lined with squamous or cuboidal epithelium, and the cystic lesion wall was mainly composed of thymic tissue with follicular hyperplasia. Based on these findings, the patient was diagnosed with MTC. To date, only 15 MTC cases have been reported in patients with HIV, and the majority of cases showed HIV infection-related symptoms such as lymphoid interstitial pneumonia and parotid gland enlargement. The present case was atypical for an HIV-related MTC because it did not involve HIV infection-related symptoms, suggesting the possibility for an alternative etiology such as COVID-19. Further reports on MTC development in patients with COVID-19 are required to elucidate the relationship between MTC and COVID-19.

Neutralizing Activity and T Cell Response after Bivalent Third Booster Dose in Plwh

Background: Aim of the study was to analyze neutralizing activity against BA.5,BQ.1.1 and T cell response after 3rd booster dose [3BD (5th shot)] with BA.4/5 bivalent vaccine by hybrid immunity (HI) and CD4 count in advanced PLWH. Method(s): In PLWH with previous AIDS and/or CD4< 200/mm3 receiving 3BD (original strain/BA.4/5),immunogenicity was assessed at time of 3BD (T0) and at day 15 (T1) by microneutralization assay [MNA90] against Omicron BA.5, BQ.1.1 and by IFNgamma-ELISA. PLWH were stratified by HI vs. nHI and by CD4 count at T0 ( >or< 500/3). For crude mean comparisons, neutralizing antibodies (nAbs) were expressed in natural scale and fold changes, IFNgamma and all values for regression analyses in log2 scale, paired t-test used to test changes over T0-T1. Two 2-arms parallel trials were emulated: HI and CD4 count as exposure, log2 nAbs and IFNgamma as outcome. Average treatment effect (ATE) of the two exposures were estimated by marginal models weighted for potential confounders (age, CD4 nadir, years from AIDS;when HI was the exposure also CD4 count). Result(s): N=48 PLWH on ART, 15% female, median age 56 yrs, 45% >1 comorbidity, 87% with previous AIDS, median CD4 nadir 44 cell/mm3 (16-102), 98% with HIV-RNA < 50 cps/mL. A significant increase of nAbs against BA.5 (fold-increase 8.8,p< 0.0001) and BQ.1.1 (6.4, p< 0.0001) was observed from T0 to T1. At T1, in nHI (n=29), mean nAb was 176 and 53 against BA.5 and BQ.1.1, respectively, with a fold change reduction (FCR) vs BA.5 of 3.3;in HI (n=19), 496 and 128, respectively, with a FCR of 3.8 (Fig.1A). After controlling for confounders, HI was associated with a higher level of neutralizing response against BA.5 [ATE=1.17 log2 (95%CI 0.34;2.00), P=0.006] but not against BQ.1.1 [0.65 log2 (-0.18;1.48), p=0.124]. At T1, among PLWH with CD4 count< 500 (n=29), mean nAb was 290.8 and 83.9 against BA.5 and BQ.1.1, respectively, with a FCR of 3.4;in those with CD4 count >500 (n=19), 230.4 and 64.3, respectively, with a FCR of 3.6 (Fig. 1C).There was no impact of CD4 count on neutralization after controlling for potential confounding factors. No evidence for a difference between T0 and T1 was detected for IFNg (Fig.1B,D). Conclusion(s): In PLWH with advanced diseases, bivalent BA.5 3BD elicited strong neutralization against BA.5, and retained cross-neutralization against BQ.1.1, even if 3 times lower. HI but not CD4 count >500 appeared to enhance neutralization against BA.5. Importantly, bivalent vaccine appeared to have no effect on T-cell mediated response. (Figure Presented).

ORIGINS OF HIV-1 AND SARS-CoV-2

Dr. Worobey will discuss the scientific evidence for when, where and how both the HIV/AIDS pandemic and the COVID-19 pandemic originated, and what we can learn from this knowledge to prevent or mitigate future pandemics?. In both cases, cross-species transmission into humans via wildlife consumption, versus via laboratory accident, were plausible hypotheses of origin. And in both cases, there is now overwhelming evidence in favor of the natural zoonosis route. Indeed, in the case of COVID-19, we have insights into the genesis of the pandemic that are in many ways unparalleled in the history of investigating pandemic origins.

Disruptions in Health Care among Mwccs Participants during the Covid-19 Pandemic

Background: The COVID-19 pandemic resulted in disruptions to health care services. Vulnerable populations, including people living with HIV (PLHIV), may have experienced unique challenges when accessing medical care. The objective of this study was to evaluate the impact of social disruptions on health care visits among Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study (MWCCS) participants. Method(s): A survey collecting data on missed health care visits and social disruptions (i.e., disruptions in employment, childcare, financial support, housing, and health insurance) during the pandemic was administered via telephone to MWCCS participants 1-3 times from March and September 2020. Logistic regression models adjusted for sociodemographics and HIV-status were used to test the association between social disruptions and three medical care interruption outcomes (i.e., missed healthcare appointment, interruption of mental health care, and interruption of substance use care). Result(s): Surveys (n=10,076) were conducted among 2238 PLHIV (61% women) and 1427 people living without HIV (PLWoH) (41% women). Overall, 42% of participants reported disruptions in health care with no significant difference by HIV status. Among participants receiving mental health care services and substance use treatment, 52% and 36% reported interruptions of care, respectively. Participants reporting >= 2 social disruptions were more likely to report missed health care appointments (adjusted odds ratio [aOR]: 1.81, 95% confidence interval [CI]: 1.54-2.13), and interruptions in mental health care [aOR: 2.42, 95%CI: 1.85-3.17) or substance use treatment (aOR: 1.97, 95%CI: 1.26-3.09), compared to those reporting no disruptions. Participants who were unemployed were more likely to miss health care appointments (aOR:1.46, 95% CI: 1.25-1.71) and report disruptions in mental health care (aOR: 2.02, 95% CI: 1.54-2.66) compared to those who were employed. PLHIV reporting >= 2 social disruptions were at increased risk for missed health care appointments (aOR 1.92, 95%CI: 1.56-2.36) and disruptions in mental health care (aOR: 2.54, 95%CI: 1.83-3.53 (Table 1). Conclusion(s): Social disruptions as a result of the COVID-19 pandemic have adversely impacted the receipt of health care among PLHIV and PLWoH, including the receipt of treatment for mental health and substance abuse. Providing childcare, financial support, housing, and health insurance may reduce disruptions in care and improve health outcomes.