Single-centre review of rapid antiretroviral therapy initiation during the COVID-19 pandemic

Background: BHIVA released interim guidance on first line anti-retroviral therapy (ART) initiation during the COVID-19 pandemic, when investigations/follow-up was restricted. Our HIV service didn't restrict follow-up but suspended in-house resistance testing (RT) due to laboratory capacity. Having prescribed 'rapid ART' based on the Northern Algorithm 01/08/2020-01/01/2022 we wanted to evaluate our prescribing during the pandemic. Method(s): All new HIV diagnoses 01/08/2020-31/12/2021 were identified via our HARS dataset. Retrospective casenote review identified ART prescribed, and switches that occurred upon baseline RT availability, to more suitable and/or cost-effective regimes. Result(s): 32 new diagnoses: 11 female, 21 male, median age 41 years (17-81), 10 MSM, 22 Heterosexuals, White British 14, African 9, other 7. Median time to ART initiation 10 days (0-210). Median CD4 count 359 (2-1251), 8 had CD4<200. 7/32 had Primary HIV infection, 5 initiating ART at 1st visit. 30/32 started ART within our service, 1 relocated, 1 initiated abroad. 28/30 started algorithm compliant rapid ART. Of the 2 that delayed, 1 had significant resistance, the other patient choice. 8/30 (27%) 'rapid ART' initiations switched post RT availability. Conclusion(s): All patients initiating ART in our service during the pandemic were algorithm compliant and fulfilled BHIVA recommendations. 7/10 starting Darunavir/ r-based therapy switched to Delstrigo post RT, a more cost-effective STR. Zero patients on Biktarvy switched post RT;implying it's difficult to switch patients from small INSTI-based-STRs. Future work includes comparing our results with other centres and reviewing ART switches post HIV National Prescribing Guide implementation. (Table Presented).

Week 48 results of a phase 3 randomized controlled trial of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs dolutegravir 1 emtricitabine/tenofovir disoproxil fumarate (DTG 1 F/TDF) as initial treatment in HIV-1/HBV-coinfected adults (ALLIANCE)

Background/Aims: The clinical course of hepatitis B virus (HBV) infection in individuals with HIV-1 coinfection is marked by accelerated disease progression. A tenofovir-containing antiretroviral regimen is recommended in most people with HIV-1/HBV-coinfection, but there have not been randomized studies of tenofovir disoproxil fumarate (TDF) vs tenofovir alafenamide (TAF) in treatment- naive HIV-1/HBV-coinfected individuals. We report primary endpoint results from a Phase 3 study comparing bictegravir/emtricitabine/ TAF (B/F/TAF) vs dolutegravir + emtricitabine/TDF (DTG + F/TDF) at Week (W)48 in participants initiating treatment for both viruses. Method(s): Adults with HIV-1/HBV coinfection were randomized 1:1 to initiate blinded treatment with B/F/TAF or DTG + F/TDF (with placebo). Primary endpoints were the proportion of participants with HIV-1 RNA<50 copies/mL (FDA Snapshot) and plasma HBV DNA<29 IU/mL (missing = failure) at W48. Noninferiority was assessed with 95% CI (12% margin). Secondary and other endpoints included change from baseline cluster of differentiation 4 (CD4) count, proportion with hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) loss/seroconversion, and alanine transaminase (ALT) normalization (AASLD criteria). Result(s): Participants (N = 243) were randomized and treated (B/F/ TAF [n = 121], DTG + F/TDF [n = 122]) from 11 countries in Asia, Europe, North, and Latin America. Baseline characteristics were median age of 32 years, 4.5% female, 88% Asian, 30% HIV-1 RNA>100,000 c/mL, 40% CD4<200 cells/lL, median HBV DNA 8.1 log10 IU/mL, 78% HBeAg+. At W48, B/F/TAF was noninferior to DTG + F/TDF at achieving HIV-1 RNA<50 copies/mL (95% vs 91%, difference 4.1%;95% CI -2.5%-10.8%;P = 0.21), with mean CD4 gains of + 200 and + 175 cells/lL, respectively. B/F/TAF was superior to DTG + F/TDF at achieving HBV DNA<29 IU/mL (63% vs 43%, difference 16.6%;95% CI 5.9%-27.3%;P = 0.0023). Participants treated with B/F/TAF vs DTG + F/TDF had numerically higher HBsAg loss (13% vs 6%;P = 0.059), HBeAg loss (26% vs 14%;P = 0.055), HBeAg seroconversion (23% vs 11%;P = 0.031), and ALT normalization (73% vs 55%;P = 0.066). The most frequent adverse events among participants treated with B/F/TAF vs DTG + F/TDF were upper respiratory tract infection (17% vs 11%), COVID- 19 (13% vs 11%), pyrexia (9% vs 12%), ALT increase (7% vs 11%), and nasopharyngitis (11% vs 4%). ALT flares (elevations at >= 2 consecutive postbaseline visits) occurred in 11 participants (7 B/F/ TAF, 4 DTG + F/TDF), and all resolved. Conclusion(s): Among adults with HIV-1/HBV-coinfection starting antiviral therapy, both B/F/TAF and DTG + F/TDF had high HIV-1 suppression at year 1, with B/F/TAF resulting in superior HBV DNA suppression and significantly more HBeAg seroconversion. Safety findings were similar between groups.

Investigation of antiviral substances in Covid 19 by Molecular Docking: In Silico Study

Aims: This paper aimed to investigate the antiviral drugs against Sars-Cov-2 main protease (MPro) using in silico methods. Material(s) and Method(s): A search was made for antiviral drugs in the PubChem database and antiviral drugs such as Bictegravir, Emtricitabine, Entecavir, Lamivudine, Tenofovir, Favipiravir, Hydroxychloroquine, Lopinavir, Oseltamavir, Remdevisir, Ribavirin, Ritonavir were included in our study. The protein structure of Sars-Cov-2 Mpro (PDB ID: 6LU7) was taken from the Protein Data Bank (www.rcsb. Org) system and included in our study. Molecular docking was performed using AutoDock/Vina, a computational docking program. Protein-ligand interactions were performed with the AutoDock Vina program. 3D visualizations were made with the Discovery Studio 2020 program. N3 inhibitor method was used for our validation. Result(s): In the present study, bictegravir, remdevisir and lopinavir compounds in the Sars-Cov-2 Mpro structure showed higher binding affinity compared to the antiviral compounds N3 inhibitor, according to our molecular insertion results. However, the favipiravir, emtricitabine and lamuvidune compounds were detected very low binding affinity. Other antiviral compounds were found close binding affinity with the N3 inhibitor. Conclusion(s): Bictegravir, remdevisir and lopinavir drugs showed very good results compared to the N3 inhibitor. Therefore, they could be inhibitory in the Sars Cov-2 Mpro target.Copyright © 2023 Oner E et al.

Modern aspects of COVID-19 in HIV-positive patients (literature review)

The article is devoted to the global problems of modern medicine - HIV infection and the COVID-19 pandemic. The review of the literature highlights current ideas about the pathogenesis and course of COVID-19 in patients with HIV infection, and also touches upon the problems of concomitant pathology and mental health of patients with HIV in the setting of the COVID-19 pandemic. It has been shown that HIV-positive patients are a risk group for the severe course of COVID-19, in particular, individuals with severe immunodeficiency (CD4+ T lymphocytes 200 cells/l) due to the development of synergetic lung damage by SARS-CoV-2 and secondary infectious agents such as cytomegalovirus and Pneumocystis carinii. It has been proven that one of the targets of the SARS-CoV-2 virus is CD4+ T cells, which in COVID-19 leads to a more rapid progression of immunodeficiency in patients with HIV infection and, thus, significantly increases the risk of secondary diseases and death. Particular attention should be paid to middle-aged and elderly people living with HIV, who, compared with HIV-negative patients, are more likely to have concomitant pathology - arterial hypertension, cardiomyopathy and diabetes mellitus, which are the risk factors for severe COVID-19. The results of studies on the effect of antiretroviral drugs on the course of COVID-19 showed that HIV-infected patients receiving tenofovir + emtricitabine have a lower risk of severe COVID-19 and associated hospitalization than patients receiving other HIV treatment regimens. Clinical and preclinical data support the potential use of tenofovir in the treatment of novel coronavirus infection.

BREAKTHROUGH HIV-1 INFECTION IN SETTING OF LONG-ACTING CABOTEGRAVIR FOR PrEP

Background: Long-acting cabotegravir (CAB-LA) is highly effective as HIV PrEP and superior to daily oral F/TDF in sexually active adults. We report a 28-yearold gender diverse patient assigned male at birth who acquired HIV-1 91 days after transitioning from F/TAF to CAB-LA despite on-time dosing. Method(s): Electronic medical records were reviewed to assess patient history and CAB-LA administration details. Plasma 4th generation HIV-1/2 Ag/Ab combination immunoassay and HIV-1 RNA quantitative PCR were performed at each injection visit. Result(s): Patient was on daily F/TAF for ten months prior to CAB-LA with acceptable adherence, missing 1 dose per week. Their medical history included hypothyroidism on levothyroxine and unconfirmed hypogonadism with illicit use of IM testosterone cypionate complicated by significantly elevated total testosterone levels. They were sexually active with cisgender men, endorsing condomless oral and anal sex with one primary partner and 20-30 unique partners per month. In the past 6 months, patient was diagnosed with syphilis and mpox. Patient was given 600mg of CAB-LA into their left gluteal medius on Day 0, 27, and 91. Day 0 and 27, plasma HIV 1/2 Ag/Ab was non-reactive and HIV-1 RNA PCR was not detected. Patient reported flu-like illness on Day 76 with positive SARS-COV-2 PCR;they completed a five-day course of nirmatrelvirritonavir with rapid resolution of symptoms. At the third injection of 600mg CAB-LA on Day 91, their plasma HIV 1/2 Ag/Ab was non-reactive but the HIV-1 RNA PCR test was detected at 1.48log c/mL. On repeat testing on Day 100, plasma HIV 1/2 Ag/Ab was reactive with HIV-1 Ab detected on differentiation assay and HIV-1 RNA PCR was detected at 1.30 log c/mL. Patient's primary partner was living with HIV resistant to NRTIs (65R, 118I) and INSTIs (92G) with undetectable plasma HIV-1 RNA for the past 24 months. Patient's viremia was below the threshold to perform standard HIV-1 sequencing;HIV-1 DNA qualitative PCR and HIV-1 proviral DNA resistance testing are currently pending. Patient ultimately started on F/TAF/DRV/COBI and DTG on Day 112. Conclusion(s): This patient's history suggests HIV-1 infection despite on-time and appropriate CAB-LA injections. To our knowledge, this is the first case of CAB-LA PrEP failure outside the setting of a clinical trial and highlights the diagnostic and management challenges that may arise with such breakthrough infections in the real world.

Effectiveness and Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Patients With HIV-1 Infection and Ongoing Substance Use Disorder: The BASE Study.

Background: People with human immunodeficiency virus (HIV) and substance use disorder (PWH/SUD) are at higher risk of nonadherence to antiretroviral therapy. Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) exhibits high rates of efficacy with a favorable adverse event profile. The BASE study (NCT03998176) is a phase 4, single-arm study evaluating the effectiveness and safety of B/F/TAF among PWH/SUD. Methods: Viremic (HIV RNA >1000 copies/mL) PWH/SUD initiated B/F/TAF once daily for 48 weeks (W). The primary endpoint was proportion of participants with HIV RNA <50 copies/mL at W24. Secondary endpoints were proportion of participants with HIV-1 RNA <50 copies/mL at W48, safety, B/F/TAF adherence (dried blood spot [DBS] concentrations of emtricitabine triphosphate and tenofovir diphosphate [TFV-DP]), substance use (NIDA-ASSIST), and quality of life (SF-12). Results: Forty-three participants were enrolled; 95% reported methamphetamine use. Median age was 38 (range, 21-62) years; 21% were female, 81% White, 14% Black, and 16% Hispanic. Thirty-two (74%) and 21 (49%) participants had HIV RNA <50 copies/mL (intention-to-treat) at W24 and W48, respectively. Seven participants (16%) experienced confirmed virologic failure through W48; 1 developed emergent drug resistance (M184V). Fifteen participants (35%) experienced grade ≥3 adverse events. Five participants (12%) reported suicidal ideation; none resulted in discontinuation. Median DBS concentrations were representative of 5-6 doses/week (TFV-DP, 1603 fmol/punches). NIDA-ASSIST scores declined from baseline to W48 with methamphetamine use decreasing most (-7.9 points; -29%), and SF-12 physical/mental scores increased 1.2 and 7.6 points, respectively. Conclusions: B/F/TAF among a high-risk population of PWH/SUD resulted in an initial 72% viral suppression rate at W24 before dropping to 49% at W48 as retention declined. One participant developed emergent drug resistance (M184V).

COVID-19 Pandemic: An Overview of its Origin, Current Status, and Ongoing Clinical Trials

The COVID-19 pandemic is raging across the globe, with the total active cases increas-ing each day. Globally over 63 million COVID-19cases and more than 1.4 million deaths have been reported to WHO. Throughout the world, academicians, clinicians and scientists are working tirelessly on developing a treatment to combat this pandemic. The origin of novel SARS-CoV-2 virus still remains foggy but is believed to have originated from a bat coronavirus RaTG13 with which it shares approximately 96% sequence similarity. In the present review, the authors have pro-vided an overview of the COVID-19 pandemic, epidemiology, transmission, developments related to diagnosis, drugs and vaccines, along with the genetic diversity and lifecycle of the SARS-CoV-2 based on the current studies and information available.Copyright © 2022 Bentham Science Publishers.

New-onset neuromyelitis optica spectrum disorder in a patient with COVID-19 and chronic Hepatitis B co-infection

Background: Neurological autoimmune disorders are often triggered by bacterial and viral infections, with growing evidence supporting coronavirus disease 2019 (COVID-19) infection precipitation of these disorders. COVID-19 is already implicated in causing discrete para-infectious neurological syndromes: acute disseminated encephalomyelitis (ADEM), transverse myelitis, neuromyelitis optica spectrum disorders (NMOSD), Guillain-Barre syndrome (GBS), and is also associated with encephalopathy, acute cerebrovascular disease, neuromuscular disorders, and seizures. Case Presentation: We describe a case of a 43-year-old Asian woman with chronic Hepatitis B (HBV) co-infected acutely with COVID-19, presenting with urinary retention, bilateral blindness, thoracic sensory level, and quadriparesis. Extensive workup narrowed down her diagnosis as seronegative NMOSD. She had complete resolution of symptoms after treatment with concurrent plasma exchange (PLEX), high dose corticosteroids, and emtricitabine-tenofovir. Follow-up visit showed no seroconversion at 6 months and no relapses. Conclusion(s): Our literature review highlights the likely link between COVID-19 infection and the development of neurologic autoimmune diseases. Our literature review supports a virus-triggered immune-mediated process rather than neuro-invasion. Many viral illnesses have been linked to the development of NMOSD and anti-AQP4 antibody-related myelitis. Additionally, there is limited literature linking chronic HBV infection with the development of optic neuritis and speculation thatcross-reactivity between HBsAg and myelin antigens may lead to the development of demyelinating diseases in the CNS and PNS. We observed remarkable clinical improvement after treatment with alternating days of IV methylprednisolone and therapeutic PLEX.Copyright © 2022

Revealing Potential Binding Affinity of FDA Approved Therapeutics Targeting Main Protease (3CLpro) in Impairing Novel Coronavirus (SARS-CoV-2) Replication that Causes COVID-19

Background: Spread of COVID-19 attains a crucial transition in reveling its pandemic across the boundaries. In combating the infection caused by SARS-CoV-2, there is a spectrum of ideal strategies that have been adopted globally, of which repurposing of approved drugs considerably having high clinical relevance. 3-chymotrypsin-like protease (3CL pro) is considered to be the potential target for the researchers as it is highly essential for cleavage of polyprotein to get 16 nonstructural proteins (called nsp1-nsp16). These proteins are highly essential for viral replication and hence become a primary target for enzyme inhibitors. 3CL pro, having a structural projectile helical chain with biologically active site involved in processing viral polyproteins that are evolved from RNA genome translation. Objective(s): The major objective of the present investigation is to evaluate the enzyme inhibition potential of FDA approved therapeutic leads in targeting 3CLpro that medicates the viral replication. Method(s): Docking calculations were carried out for an array of FDA approved molecules which leads to a notable few molecules such as Emtricitabine, Oseltamivir, Ganciclovir, Chloroquine, Baricitinib, Favipiravir, Lopinavir, Ritonavir, Remdesivir, Ribavirin, Tenofovir, Umifenovir, Carbapenam, Ertap-enem and Imipenam which have both specificity and selectivity in terms of binding efficiency against 3CL proenzyme. Result(s): A combinatorial evaluation employing in-silico screening shows a major lead for remdesivir which possesses a substantial affinity to 3CL pro binding on core amino acid residues, such as Leu 27, His 41, Gly 143, Cys 145, His 164, Met 165, Glu 166, Pro 168 and His 172 which share the biological significance in mediating enzymatic action. Results of docking simulation by Autodock over a host of FDA approved molecules show high degree of selectivity and specificity in the increasing order of binding capacity;Remdesivir> Ertapenem> Imipenam> Tenofovir> Umifenovir> Chloroquine> Lopinavir> Ritonavir> Emtricitabine> Ganciclovir> Baricitinib> Ribavirin>Oseltamivir>Favipiravir> Carbapenam. Conclusion(s): Till date, there is no known cure attained for treating COVID-19 infection. In conclusion, lead molecules from already approved sources provoke promising potential which grabs the attention of the clinicians in availing potential therapeutic candidate as a drug of choice in the clinical management of COVID-19 time-dependently.Copyright © 2020 Bentham Science Publishers.

Roll-out and effectiveness of HIV pre-exposure prophylaxis in France: An overview.

CONTEXT: Oral HIV pre-exposure prophylaxis (PrEP) has been available and fully reimbursed for people at high risk of sexually acquired HIV infection in France since January 2016. OBJECTIVE: To evaluate the roll-out of PrEP use in France and its real-life effectiveness. The main results of two previously published studies were presented at the second e-congress of the EPI-PHARE scientific interest group on pharmacoepidemiology and public decision support held in June 2022, and are reported in this article. METHODS: Two studies were carried out using the French National Health Data System (SNDS) covering 99% of the French population. A first study aimed to evaluate the roll-out of PrEP use in France from its implementation until June 2021, globally over the entire study period, including an assessment of the impact of the coronavirus disease 2019 (COVID-19) pandemic that started in February 2020 in France. A second study using a nested case-control design was conducted in a cohort of men at high risk of HIV acquisition included between January 2016 and June 2020 to assess the effectiveness of PrEP in the real world. RESULTS: As of 30 June 2021, a total of 42 159 people had initiated PrEP in France. Initiations increased steadily until February 2020, then slowed down sharply from the start of the COVID-19 pandemic and resumed from the first half of 2021. PrEP users were overwhelmingly men (98%), with an average age of 36 years, living in a large urban area (74%), and of whom a minority (7%) were socioeconomically disadvantaged. Throughout the study period, the level of PrEP maintenance from one semester to the next was high (80-90%). However, for 20% of PrEP initiators, no prescription renewals were recorded during the first six months, suggesting a substantial proportion of early treatment discontinuation. A minority (21%) of PrEP renewal prescriptions were made by private practitioners. Among 46 706 men at high risk of HIV infection, 256 patients identified with HIV infection were matched with 1213 controls. PrEP was used by 29% of cases and 49% of controls. Overall, PrEP effectiveness reached 60% (95% confidence interval 46% to 71%), and was increased in people with high PrEP use (93% (84% to 97%)), or after excluding periods of treatment discontinuation (86% (79% to 92%)). PrEP effectiveness was significantly reduced in people under 30 years of age (26% (-21% to 54%)) and in socioeconomically disadvantaged people (-64% (-392% to 45%)), for whom low PrEP uptake rates or high PrEP discontinuation rates were frequently observed. CONCLUSION: PrEP roll-out has been strongly impacted by the COVID-19 pandemic in France. Although it has been substantial among men who have sex with men, additional measures are needed to expand access to PrEP to all other population groups that could benefit from it. Promoting adherence to PrEP (especially among young people and the socioeconomically disadvantaged) will be essential to ensure a higher level of PrEP effectiveness, which has been shown to be lower in real-life settings than in clinical trials.

Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe COVID-19: The PANCOVID Randomized Clinical Trial.

BACKGROUND: This study was designed to evaluate if patients with high risk for severe COVID-19 would benefit from treatment with TDF/FTC followed by baricitinib in case of hypoxemia and systemic inflammation. METHODS: PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥ 2 comorbidities or older than 60 years conducted between 10 October 2020 and 23 September 2021. In the first randomization patients received TDF/FTC or not TDF/FTC. In the second randomization patients with room-air O2 saturation <95% and at least one increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in the number of cases and a mortality rate substantially lower than expected EudraCT registration number: 2020-001156-18. RESULTS: Of the 355 included participants 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% CI 0.52-5.91; p= 0.379); it was 0.42 (95% CI 0.11-1.59; p= 0.201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI 0.66-1.40; p = 0.774); it was 0.90 (95%CI 0.61-1.33; p = 0.687) for those treated with baricitinib. CONCLUSIONS: Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials.

TB DURING THE SEROCONVERSION PHASE

SESSION TITLE: TB and TB-Involved Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Patients who are HIV positive have a high risk of co-infection with tuberculosis (TB). Screening tests for HIV identify antibodies that are present during the seroconversion, or window phase. Here we present a case of reactivation TB during the seroconversion phase of HIV with an initially negative QuantiFERON test. CASE PRESENTATION: A previously healthy 24-year-old female presented with a productive cough. She was found to have leukopenia and apical consolidation on chest CT and was treated for community-acquired pneumonia with mild improvement of symptoms. Her QuantiFERON, COVID-19, and HIV antibody screen were negative;however, her reflex HIV antigen was positive. She re-presented a month later with a worsening cough, drenching night sweats, weight loss, vomiting, and dysphonia. Her chest CT noted a right apical cavitary lesion and bilateral upper lobe micronodules with endobronchial spreading. Her QuantiFERON and HIV antibody were now both positive. She was started on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy and on raltegravir and emtricitabine/tenofovir. DISCUSSION: Above we describe a case of reactivation TB during the seroconversion phase of HIV with a negative QuantiFERON. Primary TB presents in the middle lobes without signs of structural damage whereas secondary TB typically involves the apices and presents with cavitation. Secondary TB is typically due to reactivation or reinfection in immunosuppressed patients. Although we believe this case is due to reactivation due to radiographic findings, her initial QuantiFERON was negative. However, studies have shown that QuantiFERON may have uncertain results in latent TB infections in patients with underlying HIV (1). Reliable testing for latent TB in HIV-positive individuals is necessary as HIV increases the risk of developing active TB and TB increases the risk of transitioning from HIV to AIDS (2). CONCLUSIONS: TB is one of the top 10 causes of death worldwide and HIV is a common coinfection. To the best of our knowledge, this is the first published report of reactivation TB during the seroconversion phase of HIV with an initially negative QuantiFERON. Overall, more research must be done to identify the risk of infections during the seroconversion phase and physicians must be able to identify radiographic findings concerning for TB in patients with underlying HIV. Reference #1: Elisa Petruccioli, Teresa Chiacchio, Elisa Petruccioli, et al. Effect of HIV-infection on QuantiFERON-plus accuracy in patients with active tuberculosis and latent infection, Journal of Infection, 2020;80(5): 536-546. https://doi.org/10.1016/j.jinf.2020.02.009. Reference #2: Bruchfeld, Judith et al. "Tuberculosis and HIV Coinfection.” Cold Spring Harbor perspectives in medicine vol. 5,7 a017871. 26 Feb. 2015, doi:10.1101/cshperspect.a017871 Reference #3: Johnson JL, Okwera A, Hom DL, et al. Duration of efficacy of treatment of latent tuberculosis infection in HIV-infected adults. AIDS. 2001;15(16):2137-2147. doi:10.1097/00002030-200111090-00009 World Health Organization. Tuberculosis [Internet]. 2021 [cited 2022 Mar. 15];Available from: https://www.who.int/news-room/fact-sheets/detail/tuberculosis DISCLOSURES: No relevant relationships by Loor Alshawa No relevant relationships by Angela Binkowski No relevant relationships by Sara Qutubuddin

COVID-19 outcomes in patients with cancer and HIV: An analysis of the COVID-19 and Cancer Consortium (CCC19)

Background: Patients with SARS-CoV-2 with a diagnosis of cancer have increased risk of severe COVID-19 outcomes compared to patients without cancer. However, little is known regarding outcomes of patients with COVID-19 and cancer in the setting of human immunodeficiency virus (HIV). Given the unique risks of this population, we sought to understand COVID-19 outcomes using registry data. Methods: This is a descriptive research study utilizing the CCC19 registry, an international multi-institutional registry with healthcare provider-reported cases of patients with cancer and COVID-19. Between March 2020-December 2021, 116 persons with HIV (PWH) and 10,642 persons without HIV (PWOH) with laboratory-confirmed SARS-CoV-2 infection were identified as eligible for the analysis. Results: Median follow-up time for both groups was 90 days, with interquartile range (IQR) 30-180 days. Most PWH were actively receiving antiretroviral therapy (ART) at the time of COVID-19 diagnosis, with 71% (n = 82) having named drug information available;bictegravir/emtricitabine/tenofovir was the most common ART (n = 25). PWH were of younger age (median 57.5 yrs [IQR 46.5-63.25] vs 65 yrs [IQR 55-74]), male (81% vs 47%), and either non-Hispanic Black or Hispanic (71% vs 34%) compared to PWOH. 12% of PWH (n = 14) were current smokers compared to 6% of PWOH (n = 638), and more than half in each group were never smokers (51% of PWH and 53% of PWOH). The following comorbidities were identified in PWH vs PWOH: cardiovascular (16% vs 20%), pulmonary (16% vs 20%), renal (15% vs 14%), and diabetes mellitus (18% vs 27%). A higher proportion of PWH had hematologic malignancy compared to PWOH (33% vs 19%). More PWH had active cancer which was progressing at the time of SARS-CoV-2 infection compared to PWOH (24% vs 14%). 44% of PWH (n = 51) had received active systemic anticancer therapy within the 3 months preceding SARS-CoV-2 infection (including cytotoxic, targeted, endocrine therapies, and immunotherapy) compared to 51% of PWOH (n = 5,420). PWH had an increased rate of hospitalization (58% vs 55%) compared to PWOH. Although a lower proportion of PWH required supplemental oxygen during hospitalization compared to PWOH (34% vs 38%) and ICU admission rates were identical between the two groups (16% vs 16%), PWH had an increased rate of mechanical ventilation (14% vs 10%) and death (24% vs 18%) compared to PWOH. Conclusions: This is the first known study describing outcomes of patients with cancer and COVID-19 in the PWH population from a large multinational dataset. PWH have characteristics associated with adverse outcomes in prior analyses (male sex, non-Hispanic Black or Hispanic, hematologic malignancy, progressing cancer) but are notably younger and have fewer comorbidities. HIV infection may portend increased risk of severe COVID-19 and death;however, additional analyses, including multivariable regression, are warranted.

Assessment of a Computational Approach to Predict Drug Resistance Mutations for HIV, HBV and SARS-CoV-2.

Viral resistance is a worldwide problem mitigating the effectiveness of antiviral drugs. Mutations in the drug-targeting proteins are the primary mechanism for the emergence of drug resistance. It is essential to identify the drug resistance mutations to elucidate the mechanism of resistance and to suggest promising treatment strategies to counter the drug resistance. However, experimental identification of drug resistance mutations is challenging, laborious and time-consuming. Hence, effective and time-saving computational structure-based approaches for predicting drug resistance mutations are essential and are of high interest in drug discovery research. However, these approaches are dependent on accurate estimation of binding free energies which indirectly correlate to the computational cost. Towards this goal, we developed a computational workflow to predict drug resistance mutations for any viral proteins where the structure is known. This approach can qualitatively predict the change in binding free energies due to mutations through residue scanning and Prime MM-GBSA calculations. To test the approach, we predicted resistance mutations in HIV-RT selected by (-)-FTC and demonstrated accurate identification of the clinical mutations. Furthermore, we predicted resistance mutations in HBV core protein for GLP-26 and in SARS-CoV-2 3CLpro for nirmatrelvir. Mutagenesis experiments were performed on two predicted resistance and three predicted sensitivity mutations in HBV core protein for GLP-26, corroborating the accuracy of the predictions.

HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION PRESENTING WITH PROGRESSIVE RASH

CASE: A 25-year-old female with no medical history presented with progressive petechial rash at the chest, trunk, bilateral forearms, and thighs. Patient had the COVID-19 vaccine three weeks prior. However, denied recent travel or tick bites. No home medications nor recent hospitalizations, other than a tooth extraction a month earlier. On physical exam, the patient's vitals were unremarkable and had non-blanching petechial rash noted on her torso and bilateral extremities. Labs were significant of platelet count 1,000/mcL, hemoglobin 12.9 mg/dL, WBC 7.52 x103 /mcL, absolute lymphocytes 3.33x103 /mcL. Patient was administered two units of platelets followed by intravenous immunoglobulin (IVIG) and dexamethasone. No bleeding or hemodynamic instability was identified. Platelet count improved to 100,000/mcL over the next 24 hours. Further work-up revealed a positive HIV-1 antibody, absolute CD4 256 cells/mcL, viral load 27,300 copies/mcL. Once starting antiretroviral therapy (ART);bictegravir, emtricitabine, and tenofovir alafenamide, platelet count increased within a month to more than 200,000/mcL. IMPACT/DISCUSSION: Thrombocytopenia is defined as platelet count below 150,000/mcL. HIV-induced cytopenias are common, mainly neutropenia. However, sentinel events of thrombocytopenia are very rare in otherwise healthy individuals. A review of 5,290 HIV patients at the University of British Columbia from 1996 to 2012 revealed only 0.6% incidence of severe thrombocytopenia which they defined as platelet count <20,000/mcL. The exact pathophysiology is not clearly understood, but it is possible that antibodies against HIV cross-react with platelets or possible immune alteration. This is suggested by the prompt resolution of thrombocytopenia once ART is initiated. Immune thrombocytopenia (ITP) is a diagnosis of exclusion typically presenting with thrombocytopenia while other cell lines are normal. The greatest concern is when platelet counts drop less than 20,000/mcL due to fears of intracranial bleeding. Literature is not decisive in a correlation between platelet counts and risk of bleeding, yet it is suggested that circulating platelets are younger and more effective to maintain hematopoiesis in ITP when compared to other causes of thrombocytopenia. Treatment approach for ITP depends on the bleeding risk. In the presence of bleeding, urgent platelet transfusion, glucocorticoids, and IVIG are the mainstay of treatment. In absence of bleeding, individualized assessment of the condition is recommended to either monitor or treat. Platelet counts below 20,000-30,000/mcL require steroids or IVIG. In our case, she surprisingly presented only with minor petechial bleeding. Prompt initiation of ART, close monitoring of platelet response and CD4 count, as well as identifying resistant thrombocytopenia is indicated once patient is medically stable. CONCLUSION: Sole presentation of ITP due to HIV infection is rare. Risks of critical bleeding and further management are crucial to prevent fatal outcomes.

Roll-out of HIV pre-exposure prophylaxis use in France: A nationwide observational study from 2016 to 2021.

Background: Oral HIV pre-exposure prophylaxis (PrEP) has been available and fully reimbursed for people at high risk of sexually acquired HIV infection in France since January 2016. Its dissemination has been widely promoted to reduce HIV incidence in high-risk populations. This study aimed to assess the roll-out of PrEP use in France from its implementation until mid-2021. Methods: Using the French National Health Data System (SNDS) covering 99% of people residing in France, all PrEP users defined as individuals aged 15 years or older who received at least one dispensing of PrEP between 1 January 2016 and 30 June 2021 were identified. PrEP users number and their socio-demographic and PrEP use characteristics were assessed over time. Findings: As of 30 June 2021, a total of 42 159 individuals had initiated PrEP in France. Monthly PrEP initiations increased steadily up to 1027 in February 2020, and then slowed down sharply from the onset of the COVID-19 epidemic until a recovery in the first half of 2021. PrEP users were overwhelmingly men (97·5%, 41 126/42 159), aged 36 years on average, living in a large metropolitan area (73·8%, 31 096/42 159), and among whom a minority (7·0%, 2966/42 159) were socio-economically disadvantaged. Throughout the study period, 80-90% of users renewed PrEP from one semester to another, suggesting a good level of maintenance among those engaged in treatment. Nevertheless, for 20·1% (7148/35 549) of new PrEP users no prescription renewal was recorded in the first six months after initiation, suggesting a substantial proportion of early treatment discontinuation. Private practitioners accounted for a minority (21·3%, 77 885/366 399) of PrEP renewal prescriptions. Interpretation: PrEP roll-out has been markedly impacted by the COVID-19 pandemic in France. Although PrEP deployment has been substantial among men who have sex with men, further action is needed to expand access to PrEP to all other population groups who could benefit from it and to promote adherence to treatment. Funding: This research was carried out within EPI-PHARE without external funding.

AN AUDIT OF PATIENTS PRESCRIBED PREP USING TELEPHONE APPOINTMENTS IN A COMMUNITY SEXUAL HEALTH CENTRE DURING THE COVID-19 PANDEMIC

Introduction Our service switched routine PrEP consultations to telephone appointments from May2020 due to the Covid- 19 pandemic. We undertook an audit of revised service, on patients first prescribed Emtricitabine/Tenofovir as HIV preexposure prophylaxis (PrEP) in August/September2021. Methods Retrospective review of electronic patient records conducted on first 60 patients attending PrEP start appointment from 02/08/21-22/09/21. Demographics, referral pathway, tests performed, vaccine status and prescription outcome recorded. Results compared to national BHIVA/BASHH and service guidelines. Results 10 patients excluded: 8 on NHS-PrEP already, 2 failed criteria and did not start PrEP. All 50 patients were cis-men who have sex with men, 14% bisexual. Median age 25- 34years (range:16-55+). 93%(26/28) of documented patient ethnicity was white. Self-referrals accounted for 46%(15/33) of documented referral-routes. 25(50%) patients waited ≥2months for appointment. 46 patients prescribed NHS-PrEP met recommended BHIVA/BASHH criteria, 4(8%) failed criteria and to self-source. 36(72%) patients met BHIVA/BASHH guidelines for HIV testing, negative in 4weeks before first appointment(BFA). 73%(24/33) of patients with HIV risk after testing had repeat within 6weeks. In 3months BFA, 45(90%) patients had sexual health screen (SHS) and 26(52%) patients received hepatitis B&C testing. In 4months after, 39%(7/18) repeated hepatitis B, 54%(7/13) hepatitis C tests. 94%(29/31) patients requiring vaccinations agreed to receive. 48(96%) patients had eGFR checked in 6months BFA, no eGFR<60. Discussion Our service ensures patients meet recommended criteria for NHS-PrEP prescription and undertake renal testing and SHS. Vaccines initiated for most patients in need. Proportion of patients receiving baseline hepatitis B&C testing requires improvement. Patient pathways are being reviewed to ensure testing 2-3weeks BFA.

Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/ TAF) for the Treatment of People Living with HIV (PLWH): 12-month (12M) Effectiveness, Persistence, and Safety in a Multi-country Cohort Study

Introduction: BICSTaR (GS-EU-380-4472/GS-CA-380-4574/GS-IL-380- 5335) is an ongoing, multinational, observational cohort study evaluating real-world effectiveness and safety of B/F/TAF in ART naïve (TN) and ARTexperienced (TE) PLWH. Materials and Methods: This 12M pooled analysis included PLWH starting B/F/TAF in clinical practice from June 2018 to September 2020 (latterly during the COVID-19 pandemic) in Europe/Israel/Canada. Outcomes included virological effectiveness (HIV-1 RNA <50 copies/ml [missing=excluded]), persistence, drug-related adverse events (DRAEs), and laboratory parameters. Results: One-thousand one hundred thirty-five PLWH were included (Table 1). The TE group had older median age than TN. Of TE participants, 65%/20%/16% switched from INSTI/NNRTI/PI-based regimens (36% TDF/46% TAF/13% ABC);12% had prior virologic failure. Baseline resistance was documented in 124/535 participants (NRTI/NNRTI/PI/ INSTI=6%/6%/3%/0.2%). Prevalence of comorbidities (47%/72% TN/TE) and concomitant medication usage was high. At 12M, 97% (149/154) of TN and 96% (771/800) of TE participants had HIV-1 RNA <50 copies/ml, and persistence on B/F/TAF was high [91% (1032/1135)]. In a multivariable analysis, TE participants with neuropsychiatric disorder ongoing at baseline had lower odds for viral suppression (odds ratio=0.45, 95% CI: 0.21-0.96). There was no emergence of resistance to the components of B/F/TAF. DRAEs occurred in 13% (148/1135) of participants;gastrointestinal and neuropsychiatric DRAEs were the most common (3% each). Discontinuations due to DRAEs were low (TN 4%;TE 6%). Serious DRAEs were rare (0.2%;2 TE participants with depression). Lipidchanges are shown (Figure 1). Conclusion: B/F/TAF was associated with high levels of effectiveness and persistence after 12M in this large real-world cohort of TN and TE PLWH with a high comorbidity burden. Effectiveness was demonstrated across key subgroups (females, older participants, late presenters). Importantly, there were no new or unexpected safety findings. Collectively, these real-world data continue to support the use of B/F/TAF in clinical practice.

Patient-reported Outcome Measures at 12 Months in a Real-world Cohort of People Living with HIV with a High Prevalence of Comorbidities Receiving Bictegravir/Emtricitabine/Tenofovir Alafenamide in Europe, Canada, and Israel

Introduction: BICSTaR is an ongoing, multinational, observational cohort study evaluating B/F/TAF in ART therapy-naïve (TN) and ART-experienced (TE) PLWH. The BICSTaR population has a high baseline prevalence of comorbidities (particularly neuropsychiatric). PROs were prospectively collected. Materials and Methods: One hundred eighty TN/955 TE participants were considered for the 12M analysis (cut-off Feb 2021, including people enrolled from Jun 2018 to Sept 2020, i.e. partially during the COVID- 19 pandemic). PRO measures: Adherence [visual analogue scale (VAS)];physical/mental health [short form 36 (SF-36) questionnaire: Aggregated physical/mental component summary (PCS/MCS) scores;HIV-symptom index (HIV-SI;symptoms dichotomised into bothersome/not bothersome);HIV treatment satisfaction questionnaire (HIVTSQ;TE only);physician visits. VAS/SF-36/HIV-SI: Analysis population restricted to participants with questionnaires completed at both baseline/12M. SF-36/HIV-SI/HIVTSQ were described for participants with/without prior/ongoing neuropsychiatric comorbidities (TE only as TN subgroup was small). Results: Adherence to treatment was high at baseline (TE) and was maintained at 12M after switch to B/F/TAF [Table 1 (T1)]. Statistically significant improvements in PCS/MCS scores were observed in TN participants at 12M (p<0.05);scores remained stable in TE participants (Figure 1). The medyan (Q1, Q3) number of bothersome symptoms in TN participants declined from 6 (2, 9) at baseline to 2 (0, 6) at 12M (p<0.001;T1);TE, no change in absolute count. Statistically significant reductions in the frequency of several bothersome symptoms were reported in TN participants (p<0.05) (TE: No statistically significant changes). Treatment satisfaction was high at baseline (TE), with improvements observed at 12M following switch to B/F/TAF (p<0.001) (T1). Physician visits are shown (T1). In TE participants with baseline prior/ongoing neuropsychiatric comorbidities [275/955 (29%)], similar PRO trends were seen. Conclusion: In this real-world cohort of PLWH with a high prevalence of comorbidities (and in the setting of a global pandemic), patient-reported adherence, physical/mental health, bothersome symptoms, and treatment satisfaction were maintained/showed improvements during 12M of B/F/ TAF treatment.