T-cell immune response to SARS-CoV-2 in HIV patients.

Objective. To assess the T-cell immune status against SARS-CoV-2 in HIV patients with or without antiretroviral therapy. Patients and methods. The study included 21 HIV patients who had laboratory-confirmed COVID-19 between September and December 2021 without previous immunization against SARS-CoV-2. The characteristics of HIV infection (CD4-lymphocytes count, HIV viral load in blood plasma, the presence of antiretroviral therapy) and COVID-19 (the severity degree and duration of the disease) were analyzed, the T-cell immune response to SARS-CoV-2 was assessed using the ELISPOT method 1 month after COVID-19. Statistical analysis was carried out by non-parametric methods (Mann-Whitney U test, Spearman's rank correlation coefficient) using the IBM SPSS Statistics 22 software package. Results. The study showed a more favorable course of COVID-19 in HIV-infected persons who achieved HIV suppression in the blood: a mild form of the disease was significantly more common, and the virus was eliminated faster. T-cell immune response to SARS-CoV-2 was recorded more frequently in these patients. Significant correlation of T-cell immune status with the CD4-lymphocytes count and HIV suppression in the blood was revealed. Conclusion. Thus, T-cell immune response to SARS-CoV-2 as assessed using the ELISPOT method was registered significantl.Copyright © 2023, Dynasty Publishing House. All rights reserved.

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).

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).

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).

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.

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).

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).

Hiv Infection Increases Risk of Pasc While Covid-19 Vaccination Is Protective

Background: People with HIV (PWH) are at a higher risk of severe acute COVID-19;however, their risk of subsequently developing post-acute sequelae of SARS-CoV2 (PASC) remains unclear. Furthermore, although vaccination has been shown to be protective against PASC in the general population, few studies have evaluated its effectiveness in PWH. Method(s): We used the TriNetX health research database to source data from 69 healthcare organizations within the US. We included any adults aged >= 18 years with positive SARS-CoV-2 between January 1, 2020 and September 16, 2022 and categorized them based on their HIV status, baseline sociodemographic characteristics, comorbidities and COVID-19 vaccination status. The primary outcome was risk of PASC, compared by HIV and vaccination status after 1:1 propensity score matching. PASC was defined as either the persistence of COVID-attributable symptoms or the occurrence of new-onset health conditions at least 28 days following COVID-19 diagnosis. For all analysis, statistical significance was set at p < 0.05. Result(s): Of 3,048,792 people with confirmed SARS-CoV-2 infection, 1% (n=28,904) were PWH, with 9% of PWH (n=2592) vaccinated. At 28 days post-COVID-19 diagnosis, PWH had lower mortality compared with their non-HIV counterparts (OR 0.78, 95% CI 0.70-0.87), but higher risk of developing new-onset diabetes (DM) (OR 1.26, 95% CI 1.11-1.42), heart disease (OR 1.27, 95% 1.14-1.41), malignancy (OR 1.66, 95% CI 1.45-1.89), thrombosis (OR 1.25, 95% CI 1.12-1.39) and mental health disorders (OR 1.70 (95% CI 1.53-1.90). Furthermore, vaccinated PWH had significantly lower odds of death (OR 0.63, 95% CI 0.42- 0.93) and each new-onset PASC outcome, as follows: DM (OR 0.51, 95% CI 0.32- 0.82), heart disease (OR 0.44, 95% CI 0.29-0.67), malignancy (OR 0.43 (95% CI 0.25-0.74), thrombosis (OR 0.51, 95% CI 0.33-0.78) and mental health disorders (OR 0.49, 95% CI 0.30-0.79). The risk of PASC was higher during the pre-Delta variant period but did not vary based on CD4 count or HIV viremia. Conclusion(s): HIV infection confers a higher risk of PASC. Importantly, COVID-19 vaccination significantly lowered mortality and was protective against PASC among PWH. With the increase in the number of COVID-19 survivors, vaccination offers an effective preventive strategy to address a burgeoning public health problem. (Table Presented).

Epidemiological and Molecular Evolution of the Hiv-1 Crf94: Birth of Crf132

Background: In 2018 we reported the emergence of the new HIV-1 recombinant CRF94-02BF2 involved in a large transmission cluster of 49 French MSM mostly infected in 2016-2017. This CRF94 raised concerns of enhanced virulence. Prevention actions were undertaken in the area and population affected. This study reported the molecular and epidemiological evolution of this CRF94 until June 2022. Method(s): In 2021-2022, French sequence databases were screened for patients infected with HIV-1 subtype CRF94 or similar strain. HIV subtyping was confirmed by phylogenetic analysis of genes encoding both protease and reverse transcriptase (1070bps), and integrase (696bps) using IQ-Tree. Five whole genomes, related but distinct from CRF94, were obtained with the DeepChek assay Whole Genome kits. Recombination breakpoints were estimated using RDP4 and SimPlot. Mann-Whitney and LogRank tests were used for statistical analyses to compare patients' characteristics. Result(s): In June 2022, 49 new HIV-1 sequences were collected: 14 clustered with the 49 previous CRF94, 32 formed a new cluster next to but distinct from CRF94, and 3 strains could not be classified. Analysis of 5 whole genomes from the new cluster revealed a new recombinant, the CRF132-94B, mainly consisting of CRF94 which recombined with subtype B in the POL and accessory genes. Vif gene changed from the F2 to the B subtype. Both CRF94 and 132 clusters involved >95% of MSM, mostly infected < 1 year before diagnosis. However, there were differences: 97% were diagnosed in 2013-2019 for CRF94 vs 90% in 2020-2022 for CRF132. At time of diagnosis, 33% of patients infected with CRF94 knew the Prep vs 95% for CRF132. In the cluster CRF94, patients were older (34 vs 30 years, p=0.02), had higher viral loads (5.42 vs 4.42 log10 copies/Ml;p< 0.001), a lower CD4 cell counts (358 vs 508 /mm3, p=0.002). On treatment, the patients with the CRF94 reached viremia < 50 copies/Ml significantly later than those infected with CRF132 (p=0.0002). The prevention activities targeting the CRF94 cluster could explained the few patients infected with this strain after 2018. The CRF132 is mainly located in another Paris region area, but no specific transmission place has been identified. Conclusion(s): After 2019, the CRF94 spread seems greatly slowed down but the very close CRF132-94B has given birth to a new highly active cluster in 2020- 2022, despite the COVID social-distancing and a strong knowledge of the Prep. CRF132 appears to be less virulent perhaps due to the Vif gene change. Identified breakpoints positions of the new HIV-1 CRF132-94B. GenBank accession numbers of the five references : ON901787 to ON901791.

REACTOGENICITY AMONG PEOPLE LIVING WITH HIV AFTER mRNA-1273 VACCINE IN UBUNTU STUDY

Background: The tolerability of mRNA COVID-19 vaccines among people living with HIV (PLWH) has been understudied in vaccine trials. CoVPN 3008 (Ubuntu) is the largest multicenter Phase 3 efficacy trial of mRNA vaccines in sub-Saharan Africa. Method(s): We enrolled adults age >=18 years living with HIV or another comorbidity associated with severe COVID-19. Previously vaccinated individuals were excluded. Baseline testing included HIV, CD4 count and HIV viral load (VL) (if HIV+), anti-SARS-CoV-2 antibodies, and nasal swab SARS-CoV-2 nucleic acid amplification test (NAAT). All participants receive vaccinations at months 0 and 6, and SARS-CoV-2 seronegative individuals also receive vaccination at month 1. This analysis includes mRNA-1273 vaccinations at months 0 and 1. Reactogenicity (solicited adverse events [AEs]) was assessed among a representative subset of participants (Safety Subset, SS) for 7 days post-vaccination. Baseline characteristics associated with moderate/severe reactogenicity events were assessed by univariate and multivariate logistic regression. Result(s): 14002 participants were enrolled in the trial (1510 into the SS) at 46 sites from 2 Dec 2021 to 9 Sep 2022. At baseline in the SS, 71% (1065) were female, median age 38 years (IQR 32-46), and median BMI 25.0 (IQR 20.7-30.2). 73% (1108) were SARS-CoV-2 seropositive, and 8.7% (131) had a positive nasal NAAT swab. 16% (197) had a history of tuberculosis. 84% (1267) were PLWH, with median CD4 count of 614 cells/muL (IQR 414-861);7.8% had CD4 count < 200. 21% (238) had detectable HIV VL (>=50 copies/mL), with median VL 1660 (IQR 182-23932). 14% (172/1262) and 12% (64/542) of PLWH reported moderate/severe reactogenicity after the 1st and 2nd vaccination (Figure), with no hospitalizations. Female PLWH and CD4 count >500 had 35% (p=0.03) and 44% (p=0.04) increased odds of moderate/severe reactogenicity, respectively. Other baseline characteristics were not associated with the odds of reporting moderate/severe reactogenicity among PLWH after 1st vaccination. Similar trends were seen after the 2nd vaccination, but none reached statistical significance. In multivariate models, female sex remained associated with increased odds of moderate/severe reactogenicity after the 2nd vaccination. Conclusion(s): Similar to observations in HIV-negative populations, mRNA-1273 was well tolerated by PLWH with more reactogenicity in females. Impaired inflammatory responses among participants with CD4 counts < 500 cell/muL may explain less moderate/severe reactions.

Impact of Hiv Infection on Mpox-Related Hospitalizations in Brazil

Background: Late presentation to care remains a major public health problem in Brazil, despite the countrys longstanding commitment to universal access to ART to all PLWH. The COVID-19 pandemic severely hit the country and further impacted the HIV care continuum, with worse disparities observed by gender and sexual orientation. By December 28th 2022, Brazil reported 10,493 and 14 mpox cases and deaths ranking second globall. Although mpox lethality is low, HIV-related immunosuppression may negatively impact mpox outcomes, increasing hospitalizations and fatalities. We aim to describe mpox hospitalization rates and explore the impact of HIV-infection on mpox-related hospitalizations and clinical outcomes. Method(s): Prospective, observational cohort study of individuals with confirmed mpox infection followed at the major mpox referral center in Rio de Janeiro, Brazil. Demographic and clinical data including reasons for hospitalization were systematically collected. Chi-squared or Fisher's exact tests for qualitative variables and the Moods median test for quantitative variables were used. Result(s): From June 12 to December 12, 2022, 402 participants had a laboratory-confirmed mpox diagnosis. Median age was 34 years, 365 (91%) were cisgender men, and 197 (49%) were PLWH. Overall, 39 (10%) participants were hospitalized due to mpox-related causes;20 (51%) were PLWH. All PLWH with CD4 counts< 200 cells/mm3 required hospitalization. Compared to nonhospitalized PLWH, a higher proportion of hospitalized PLWH had concomitant opportunistic infections (4/20 [20%] vs. 1/177 [0.6%];p< 0.001), were not virologically suppressed (7/20 [35.0%] vs. 22/177 [15.3%];p=0.1) and were not on ART (4/20 [20%] vs. 15/177 [7.6%];p=0.03). Among all hospitalized participants, PLWH were more frequently hospitalized due to severe proctitis than HIV-negative participants (12/20 [60%] vs. 5/19 [26.3%];p=0.03), with no differences regarding hospitalizations for pain control (Table). PLWH accounted for all cases of hospitalized individuals who required intensive care support (n=4), had deep tissue involvement (n=3) and had a mpox related death (n=2). Conclusion(s): Our findings suggest an association between worse outcomes in the HIV care continuum and mpox-related hospitalizations. Advanced immunosuppression (CD4< 200) contributed to more severe clinical presentations and death. Public health strategies to mitigate HIV late presentation and the negative impact of the COVID-19 pandemic to the HIV care continuum are urgently needed. Sociodemographic and clinical characteristics of mpox cases according to HIV and hospitalization status.

Effectiveness of Dolutegravir in People on Rifampin-Based Tuberculosis Treatment

Background: Tenofovir-lamivudine-dolutegravir (TLD) is the WHO-preferred first-line regimen for people with HIV, but drug-drug interactions between dolutegravir (DTG) and rifampin (RIF) require an additional 50mg DTG (TLD+50) in people receiving tuberculosis (TB)/HIV co-treatment. RIF is a key drug in TB treatment, but is a potent inducer of metabolizing enzymes and efflux transporters, which can markedly lower drug concentrations. There are limited data on the effectiveness of TLD+50 in people with TB/HIV from program settings. Method(s): We conducted a prospective, observational study at 12 sites in 6 countries (Haiti, Kenya, Malawi, South Africa, Uganda, Zimbabwe). Participants received concomitant TLD+50 and RIF-based TB treatment provided as standard of care by HIV and TB treatment programs. Primary outcome was HIV-1 RNA <1000 copies/mL (cpm) at end of TB treatment. New DTG resistance mutations were defined as those present at end of TB treatment but not present at start. Result(s): From 11/2019-6/2021, we enrolled 91 participants with TB/HIV, including 75 ART-naive participants (82%) starting TLD+50 after a median of 15 days on TB treatment, 10 ART-naive participants (11%) starting TLD+50 and RIF together, 5 (5%) starting TB treatment and changing to TLD+50 after a median of 3.3y on TLD, and 1 (1%) starting RIF and TLD+50 after changing from EFV/3TC/TDF. Median age was 37y (IQR 32-43), 35% were female, 100% cis-gender, median CD4 count was 120 cells/mm3 (IQR 50-295), 87% had HIV-1 RNA >1000 copies/mL. Two participants died during TB treatment (week 4 disseminated TB, week 12 suspected COVID-19), 1 interrupted TLD+50 due to jaundice;and 1 discontinued TB treatment due to drug-induced liver injury. Among 89 surviving participants, 6 were lost to follow-up and a further 10 had no HIV-1 RNA result due to missed or remote visits. Primary virologic outcome was therefore assessed in 73 (80%), of whom 69 (95%, Wald 95% CI 89-100%) had HIV-1 RNA <=1000 cpm;68 (93%) had HIV-1 RNA <200 cpm. No sex specific differences in viral suppression were observed. No DTG resistance mutations were detected among 4 participants with HIV-1 RNA >1000 cpm. Conclusion(s): Concomitant RIF-containing TB treatment and TLD+50 was welltolerated and achieved excellent viral suppression in a cohort of predominantly ART-naive people with TB/HIV. These multi-country data from program settings support feasibility and effectiveness of current treatment approaches for TB/ HIV co-infection.

Fanmi: A Randomized Trial of Community Cohort Hiv Care for Adolescent Girls, Haiti

Background: Adolescent girls and young women are the epicenter of the global HIV epidemic and in need of multilevel interventions to improve their health outcomes. Method(s): FANMI, a randomized-controlled trial, evaluated the effectiveness of community-based cohort HIV care versus standard of care (SOC) among adolescent and young adults living with HIV (AYALH) in Haiti. Females, 16-24 years who were newly diagnosed with HIV at clinic or community HIV testing sites, or defaulted >6 months from care, were randomized 1:1 to FANMI vs SOC. FANMI was designed to improve convenience, social support and stigma by grouping AYALH in cohorts of 6-10 peers to attend monthly HIV care sessions in a community center with integrated clinical care, group counseling, and social activities led by the same provider. National guideline changes during the study included switching participants to dolutegravir regimens and expanding SOC visits to 6 months. The primary outcome was 12-month retention defined as any visit 9-15 months from enrollment. Secondary outcomes included viral suppression (< 1000 copies/ml), risk behaviors, and acceptability using interviews. Result(s): 120 AYALH enrolled (60 per arm) between May 2018-January 2021. Median age was 21, 91% were newly diagnosed, and median CD4 count was 591 cells/mm3 (IQR 399-788). A total of 78.3% (47/60) FANMI participants vs 85.0% (51/60) in SOC achieved the primary outcome (unadjusted RR=0.92 95%CI 0.78-1.09, p=0.35). Excluding 9 participants who never attended a FANMI/SOC visit after enrollment, 12-month retention was 88.7% (47/53) in FANMI vs 87.9% (51/58) in SOC (RR =1.01 95%CI 0.88-1.15, p=0.90). Participants who presented for HIV testing vs community testing and achieved the primary outcome: 95% vs 70% (FANMI) and 83% vs 88% (SOC). Viral suppression among those retained at 12 months: 44.6% (21/47) in FANMI and 37.3% (19/51) in SOC (RR 1.20 95% CI 0.74-1.9, p=0.45). There were no differences in pregnancy and risk behaviors. Providers preferred FANMI reporting increased time for counseling and peer support. FANMI participants reported high acceptability, decreased stigma, and increased social support with no confidentiality breaches. Limitations included interrupted study operations during the COVID-19 pandemic. Conclusion(s): FANMI was not more effective for AYALH in Haiti but was preferred by providers and highly acceptable to participants. It offers promise as a complementary program for high-risk AYALH in low-income settings facing barriers to clinic-based care.

IMMUNOGENICITY OF SARS-CoV-2 mRNA VACCINATION IN IDIOPATHIC CD4 LYMPHOPENIA

Background: The rapid development of SARS-CoV-2 mRNA vaccines has been a remarkable success of the COVID-19 pandemic, but vaccine-induced immunity is heterogeneous in immunocompromised populations. We sought to determine the immunogenicity of SARS-CoV-2 mRNA vaccines in a cohort of people with idiopathic CD4 lymphopenia (ICL). Method(s): 25-patients with ICL followed at the National Institutes of Health on a natural history protocol were evaluated between 2020-2022. Blood and serum was collected within 4-12 weeks after their second and/or third SARS-CoV-2 mRNA vaccine dose. Twenty-three matched healthy volunteers (HVs) provided blood samples at similar timepoints post-mRNA vaccination on a separate clinical protocol. Pre-vaccine blood samples were also used when available. Anti-spike and anti-receptor binding domain antibodies were measured. T-cell stimulation assays were performed to quantify SARS-CoV-2 specific T-cell responses. Comparisons were made with Wilcoxon test. Result(s): Twenty-participants with ICL had samples collected after their second mRNA vaccine and 7-individuals after the third dose. Median age at vaccination was 51-years (IQR: 44-62) and 12 were women (48%). Median CD4 T-cell count was 150 cells/muL (IQR: 85-188) at the time of vaccination, and 11-individuals (44%) had a baseline CD4 count <=100 cells/muL. HVs had a median age of 54-years (IQR: 43-60) with 13-women (56.5%). Anti-spike IgG antibody levels were significantly greater in HVs than those with ICL after 2-doses. Lower SARS-CoV-2 IgG antibody production was primarily observed in those with baseline CD4 T-cells <=100 cells/mul (Figure-1A). The decreased production in ICL remained after a third vaccine dose (Figure-1B). There was a significant correlation between anti-spike IgG and baseline CD4 count. Spike-specific CD4 T-cell responses in volunteers compared to those with ICL demonstrated similar levels of activation induced markers (CD154+CD69+) and cytokine production (IFNgamma+, TNFalpha+, IL2+) after two or three mRNA vaccine doses. Quantitatively the smallest responses were observed in those with lower baseline CD4 T-cells (Figure 1C-D). Minimal SARS-CoV-2 CD8 T-cell responses were detected in both groups. Conclusion(s): Patients with ICL and baseline CD4 T-cells >100 mount similar humoral and cellular immune responses to SARS-CoV-2 vaccination as healthy volunteers. Those with baseline CD4 T-cells <=100 have impaired vaccine- induced immunity and should be prioritized to additional boosters and continue other risk mitigation strategies. (Figure Presented).

A comprehensive review on the diagnosis and testing strategies for coronavirus disease

The COVID-19 outbreak has fashioned to severe threat to each and every individual in social and economic aspects in the country. This required improved wisdom to know how it is different and dominant, to diagnose and determine effective vaccines to avoid the transmission of these deadly causative agents. From this review, the probable property of these deadly transmissible viruses is related to that of SARS-CoV-2 as a fright zone of viruses. It also provides some sparks about effective and accurate diagnosis and treatment strategies. The effective management and control of panic zone of virus (PZV) and SARS-CoV-2 are more important to reduce the pandemic situation.Copyright © 2023 Inderscience Enterprises Ltd.

Covid-19 Vaccination Impacts Functional Immune Responses and Plasma Proteome in Plwh

Background: The impact of COVID-19 infection or COVID-19 vaccination on the immune system of people living with HIV (PLWH) is unclear. We therefore studied the effects of COVID-19 infection or vaccination on functional immune responses and systemic inflammation in PLWH. Method(s): Between 2019 and 2021, 1985 virally suppressed, asymptomatic PLWH were included in the Netherlands in the 2000HIV study (NCT039948350): 1514 participants enrolled after the start of the COVID-19 pandemic were separated into a discovery and validation cohort. PBMCs were incubated with different stimuli for 24 hours: cytokine levels were measured in supernatants. ~3000 targeted plasma proteins were measured with Olink Explore panel. Past COVID-19 infection was proven when a positive PCR was reported or when serology on samples from inclusion proved positive. Compared were unvaccinated PLWH with and without past COVID-19 infection, and PLWH with or without anti-COVID-19 vaccination excluding those with past COVID-19 infection. Result(s): 471 out of 1514 participants were vaccinated (median days since vaccination: 33, IQR 16-66) and 242 had a past COVID-19 infection (median days since +PCR: 137, IQR 56-206). Alcohol, smoking, drug use, BMI, age, latest CD4 count and proportion with viral blips were comparable between groups. Systemic inflammation as assessed by targeted proteomics showed 89 upregulated and 43 downregulated proteins in the vaccinated participants. In contrast, individuals with a past COVID-19 infection display lower levels of 138 plasma proteins compared to the uninfected group (see figure). 'Innate immune system' and 'cell death' were upregulated in pathway analysis in vaccinated PLWH, but downregulated in COVID-19 infected participants. The increased systemic inflammation of the COVID-19 vaccinated group was accompanied by lower TNF-alpha and IL-1beta production capacity upon restimulation with a range of microbial stimuli, while production of IL-1Ra was increased. In COVID-19 infected PLWH only a reduced production of TNF-alpha to S. pneumonia was significant. Vaccinated PLWH also showed upregulation of platelet aggregation pathways. Conclusion(s): COVID-19 vaccination in PLWH leads to an increased systemic inflammation, but less effective cytokine production capacity of its immune cells upon microbial stimulation. This pattern is different from that of COVID-19 infection that leads to a decreased inflammatory profile and only minimal effects on cytokine production capacity. (Figure Presented).

High Mortality in Hospitalised Virally Suppressed Adults with Hiv in South Africa

Background: Mortality in PWH has been markedly improved by antiretroviral therapy (ART) but there are few reports describing this in the ~5 million virally suppressed (VS) PWH in South Africa(SA). We describe cause of death(CoD) in adults admitted to hospital with suspected pneumonia in SA. Method(s): We enrolled patients from June 2019-October 2021 at four hospitals and then followed them up for >=1 year. Eligibility included: Age >18 years, >=2 signs/symptoms of pneumonia, < 48 hrs since admission. Medical records were reviewed. All had HIV status ascertained and sputum sent for Xpert Ultra and mycobacterial culture. In PWH CD4 count, viral load (VL) and urine lipoarabinomannan were assessed. For those who died, CoD were ed from medical charts and interview of family. We categorised deaths as early: while admitted or to < 30 days after discharge;or late: >=30 days after discharge. We report mortality and CoD in VSPWH (VL<=50 copies/ml), unsuppressed and HIV uninfected(HUI) adults. Result(s): Of 1999 adults, 54% were PWH;61.2% reported receiving ART of whom 43.1% were VS;55.5% were women. Overall median age of VS was 48 years (IQR: 40-55) at entry;34.3% had comorbidities: hypertension (70.1%, obesity 41.3%, diabetes 28.9%) . Only 11.3% were diagnosed with HIV in the past year, 35.0%, had prior TB. Median CD4 count of VS patients was 289 cells/ mm3 (IQR:133-490) and Hb, 12.5g/dL (IQR:10.5-14.0);53.0% had CRP >100mg/ dL and 69.6% had oxygen saturation < 93% on room air;14.8% had >=1 assay positive for TB;and 42.9% were SARS-CoV-2 positive. Overall 25.4% VSPWH died compared to 31.2% and 22.9% of unsuppressed and HUI, respectively;median ages at death were 49 (IQR:43-59), 38 (IQR: 32-47) and 62 (IQR: 53-69) years respectively. Overall median times to early and late death was 8 (IQR: 4-16) and 104 (IQR: 75-254) days, respectively. The leading CoD in VSPWH were: COVID-19 (22.9%), chronic lung disease(CLD) (17.1%),malignancy (12.9%),sepsis, (12.9%) and TB (8.7%);in HIV unsuppressed, CoD were: advanced HIV and opportunistic infections-(TB,PJP)(55.5%), sepsis(9.6%), COVID-19(8.6%);and in HUI: COVID- 19(43.0%), cardiovascular disease (9.0%), TB(9.0%), malignancy (8.5%). Conclusion(s): Mortality in VSPWH admitted with suspected pneumonia was higher than in HUI and occurred 12 years earlier. The challenge for clinicians is to screen for diseases that disproportionately affect VSPWH and to try to prevent recurrent lung infections thereby increasing their comorbidity-free years and reduce mortality gaps.

12-MONTH HUMORAL RESPONSE AFTER mRNA COVID-19 VACCINATION IN PEOPLE LIVING WITH HIV

Background: We compared the 12-month post primary vaccination humoral immune response to mRNA COVID-19 vaccines in PLHIV and controls. Method(s): PLHIV and HIV-negative healthy controls included in the French national multi-center prospective COVID 19 vaccine cohort study ANRS0001S COV-POPART were analyzed. Percentage (95% CI) of responders (positive anti- Spike SARS-CoV-2 IgG antibodies) and geometric means titers (95% CI) of anti-Spike SARS-CoV-2 IgG antibodies (BAU/mL) were assessed at 1 month and 6 months (M) after the 2nd dose of the primary vaccination and at 12 months in those who received a booster dose. Specific neutralizing antibodies (nAbs) (in vitro neutralization assay against original, Delta and Omicron BA.1 strains) were estimated in a subset of participants. Serological tests (ELISA Euroimmun) and seroneutralization were performed centrally. Result(s): Overall, 858 PLHIV and 1156 controls were included. PLHIV were older than controls: 55.2 years, (49.6-60.6) vs 46.6 years (36.3-56.6) and more frequently male (75.1% vs 48.9%). Among PLHIV at inclusion, 97.3% were under antiretroviral therapy, 95.6% had an undetectable viral load and 71.8% had CD4 counts above 500 cells/mm3. Participants had namely received BNT162b2 as the primary vaccination (93% in PLWHIV vs 84% in controls) and 53.1% had received a booster dose (57.2% in PLHIV (median time after the 2nd dose: 6.1 M [5.9-6.7]) and 50.1% in controls (median time 6.0 M [5.5-6.2])). Percentage of responders after the 2nd dose was lower in PLHIV than controls ((98.7% [97.7;99.3] vs 99.9% [99.5;99.9], p=0.0001)). PLHIV had significantly lower levels of anti-Spike antibodies at 1 M ((1188 [650;2067] vs 1506 [950;2507] BAU/mL, p< 0.0001)) and 6 M (149 [95;235] vs 194 [124;314] BAU/mL, p=< 0.0001) but similar levels at 12 M (520 [269;1198] vs 427 [259;1087] BAU/mL, p=0.3387) (Figure A). PLHIV had significantly lower nAbs against original, Delta and Omicron BA.1 strains at 1, 6 and 12 M after primary vaccination compared to controls. The booster dose significantly increased the titers of nAbs against original and Delta strains and, to a lower extent, against Omicron (Figure B). Conclusion(s): PLHIV had high response rates to mRNA COVID-19 vaccines but lower titers of antibodies and nAbs at 1 and 6 M after primary vaccination than controls. One mRNA booster dose increased SARS-CoV-2 IgG antibodies titers to similar levels to controls but neutralizing activity especially against Omicron remained lower. (Figure Presented).

SARS-CoV-2 IN CHILDREN & ADOLESCENTS LIVING WITH HIV IN EUROPE & SOUTH AFRICA

Background: Adults living with HIV may have higher risk of SARS-CoV- 2 infection than HIV negative adults. There are no published data on seroprevalence of SARS-CoV-2 in children and adolescents living with HIV (CALWHIV). Method(s): We did a repeat SARS-CoV-2 seroprevalence study in 7 paediatric HIV observational cohorts in 5 countries in the European Pregnancy & Paediatric Infections Cohort Collaboration (EPPICC;Belgium, Greece, Spain, Ukraine, United Kingdom (UK)) and also the Cape Town Adolescent Antiretroviral Cohort (CTAAC), South Africa (SA) (CALWHIV and HIV negative adolescents). Participants gave 2 blood samples for SARS-CoV-2 antibody testing ~6 months apart during routine visits between May 2020 and July 2022, and completed questionnaires on SARS-CoV-2 exposure/infection and vaccine status. Clinical and demographic data were extracted from clinic records. Result(s): Of 906 participants, 53%(477) were female, 89%(803) CALWHIV, median [IQR] age at first visit 17[15-19] years. Most were enrolled in SA (45%, 410/906), UK (23%, 205/906) or Ukraine (18%, 160/906). 85%(767/906) had 2 blood samples and the rest a single sample. For CALWHIV, at time of first sample, 99%(761/765) were on antiretroviral therapy, median CD4 count was 666[478-858] cells/mL, 70%(535/764) had HIV-1 viral load < 50c/mL. Of those with known SARS-CoV-2 vaccine status, 23%(181/773) CALWHIV and 22% (22/100) HIV negative participants received >=1 vaccine dose. 6%(43/762) of CALWHIV had a documented prior SARS-CoV-2 positive PCR (including 2 hospitalised for COVID, neither severe), and 16%(124/762) self-reported previous positive test and/or COVID-19 symptoms, giving a total of 17%(128/762) with any previous infection. Based on serum testing, 63%(562/898) of participants overall were seropositive on at least one sample (55% (269/488) Europe, 67% (205/307) SA CALWHIV, 85% (88/103) SA HIV negative group), and among the unvaccinated subgroup, 53%(408/765) were seropositive (41% (167/412) Europe, 64% (168/263) SA CALWHIV, 81% (73/90) SA HIV negative). Among samples taken prior to or in absence of vaccination, the proportion testing antibody positive increased over time (Figure). Of unvaccinated CALWHIV with >=1 positive result, 17%(52/299) reported any previous SARS-CoV-2 infection. Conclusion(s): Most CALWHIV were SARS-CoV-2 seropositive by mid-2022 despite low vaccine coverage. Fewer had documented or self-reported COVID-19 infection or disease, suggesting most infections were mild or asymptomatic. Seroprevalence of SARS-CoV-2 antibodies in Europe and South Africa, by HIV status and calendar quarter of sampling. Colours indicate dominant variant based on GISAID data for adults and children.

Covid-19 Vaccine Coverage among People with Hiv in the Vaccine Safety Datalink

Background: People with HIV (PWH) may be at increased risk for severe COVID-19 outcomes compared with people without HIV. However, COVID-19 vaccination coverage among PWH is largely unknown, especially among those with advanced HIV or comorbidities. Method(s): We conducted a cohort study to evaluate coverage of the initial COVID-19 vaccine primary series and factors associated with the completion in adult PWH (>=18 years) enrolled in 8 healthcare organizations participating in the Vaccine Safety Datalink (VSD) project during December 1, 2020- December 31, 2021. Completion of two doses of the Pfizer-BioNTech or Moderna mRNA COVID-19 vaccines or one dose of the single-dose Janssen COVID-19 vaccine was assessed. Multivariable analysis was conducted using a robust Poisson regression model to estimate the rate ratio (RR) for factors associated with primary series completion, accounting for follow-up time. Result(s): A total of 22,063 PWH were identified, among which 89% were male and 93% were viral suppressed (viral load, VL <=200 copies/ml). Chronic comorbid conditions were prevalent, with 25% having a Charlson comorbidity score of 1-2 and 13% having a score of 3 or greater. About 23% were overweight and 17% were obese. The majority (90%) completed the primary series and 1,782 PWH (8%) did not receive any dose during the study period. A rapid uptake was achieved within the 6 months after the national COVID-19 vaccination program launched on December 14, 2020. (Figure 1) PWH who received one dose of mRNA vaccine (i.e., partially vaccinated) were excluded (n=314) from the analysis for the primary series completion. Having received an influenza vaccination in the past 2 years was the strongest predictor of completion (RR=1.17, 95%CI: 1.15, 1.20). Males (RR= 1.06, 95%CI: 1.04-1.08) and those of Asian race (RR=1.05, 95%CI: 1.03-1.06, vs. White) were more likely to complete the primary series. However, PWH with baseline CD4 counts < 200 (RR=0.97, 95%CI: 0.94-0.99) and those failing to achieve viral suppression (VL= 201-10k: RR= 0.89, 95%CI: 0.85-0.94;VL >10k: RR= 0.92, 95%CI: 0.87-0.98) were less likely to complete the primary series. Body mass index, Charlson comorbidity score, and neighborhood household income level were not associated with completion. Conclusion(s): Coverage of the COVID-19 vaccine primary series was high in adult PWH in the VSD. However, targeted vaccination outreach is warranted for PWH with low CD4 counts and uncontrolled HIV viral load.