Elizabeth Nalintya et al.

Effect of Coronavirus Disease 2019 Lockdowns on Identification of Advanced Human Immunodeficiency Virus Disease in Outpatient Clinics in Uganda

CID, February 2023 ; doi.org/10.1093/cid/ciad087

Abstract

Using data from 67 Ugandan human immunodeficiency virus (HIV) clinics (July 2019–January 2022), we report a 40% (1005/1662) reduction in the number of people with HIV presenting to care after August 2021 compared to prepandemic levels, with a greater proportion presenting with advanced HIV disease (20% vs 16% in the pre–coronavirus disease 2019 period).

Willem Marcelle Jagga et al.

Point of care ultrasound findings in critically ill SARS-COV2 patients in an HIV endemic, resourced constrained setting

Cell, May 2023; doi.org/10.1016/j.heliyon.2023.e16519

Abstract

To describe the incidence of venous thromboembolism (VTE) in mechanically ventilated COVID-19 patients in an HIV endemic, resourced constrained setting. To describe the incidence of VTE in relation to HIV status and anticoagulant therapy, and to evaluate VTE-associated cardio-respiratory changes. To establish the contribution of HIV, anticoagulation therapy and other risk factors to mortality.

Design

Prospective descriptive study.

Setting

Single-center tertiary teaching hospital.

Participants

One hundred and one consecutively admitted critically ill adult patients with COVID-19 acute respiratory distress syndrome.

Interventions

Point of care ultrasound (POCUS) assessment of the lower limbs and the cardio-respiratory system was performed on intensive care unit (ICU) admission and repeated if clinically indicated.

Measurements and main results

DVT was diagnosed by POCUS, whilst pulmonary embolism was diagnosed using a combination of clinical criteria and POCUS (echocardiography and chest wall ultrasound). VTE was diagnosed in 16/101 (16%) patients, despite 14/16 (88%) receiving prior therapeutic dosage of low molecular weight heparin. Clinically significant PE was diagnosed in 5/16 (31%) with 11/16 (69%) having DVT only. The majority of VTE patients, 12/16 (75%), demised 16/101 (16%) patients had HIV co-infection, and 4/16 (25%) with HIV had VTE. Valvular abnormalities were the most common cardiac abnormality with marked tricuspid regurgitation detected in 51/101 (51%). The absence of right atrial enlargement had a 93% negative predictive value for the absence of VTE. Univariate analysis did not demonstrate statistically significant individual risk factors for mortality.

Conclusions

Mechanically ventilated COVID- 19 patients at ICU admission had a low incidence of VTE (16%). Therapeutic dose anticoagulation did not reduce mortality compared to prophylactic dosage. In contrast to findings from other studies, no individual risk factor contributed significantly to mortality, likely due to small sample size. POCUS is an ideal screening tool to aid in the assessment of critically ill patients.

Tianming Zhao et al.

The influence of the COVID-19 pandemic on identifying HIV/AIDS cases in China: an interrupted time series study

The Lancet, April 2023; doi.org/10.1016/j.lanwpc.2023.100755

Abstract

The COVID-19 pandemic has caused significant global public health challenges, and impacted HIV testing and reporting worldwide. We aimed to estimate the impact of COVID-19 polices on identifying HIV/AIDS cases in China from 2020 to 2022.

Interpretation

The COVID-19 pandemic influenced the allocation and acquisition of medical resources which impacted accurate monthly reporting of HIV in China. Interventions that promote continuous HIV testing and ensure the adequate provision of HIV services including remote delivery of HIV testing services (HIV self-testing) and online sexual counseling services are necessary during pandemics in future.

Fidler S et al.

Booster Vaccination Against SARS-CoV-2 Induces Potent Immune Responses in People With Human Immunodeficiency Virus

CID, January 2023; doi.org/10.1093/cid/ciac796

Abstract

Background

People with human immunodeficiency virus (HIV) on antiretroviral therapy (ART) with good CD4 T-cell counts make effective immune responses following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are few data on longer term responses and the impact of a booster dose.

Methods

Adults with HIV were enrolled into a single arm open label study. Two doses of ChAdOx1 nCoV-19 were followed 12 months later by a third heterologous vaccine dose. Participants had undetectable viraemia on ART and CD4 counts >350 cells/µL. Immune responses to the ancestral strain and variants of concern were measured by anti-spike immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), MesoScale Discovery (MSD) anti-spike platform, ACE-2 inhibition, activation induced marker (AIM) assay, and T-cell proliferation.

Findings

In total, 54 participants received 2 doses of ChAdOx1 nCoV-19. 43 received a third dose (42 with BNT162b2; 1 with mRNA-1273) 1 year after the first dose. After the third dose, total anti-SARS-CoV-2 spike IgG titers (MSD), ACE-2 inhibition, and IgG ELISA results were significantly higher compared to Day 182 titers (P < .0001 for all 3). SARS-CoV-2 specific CD4+ T-cell responses measured by AIM against SARS-CoV-2 S1 and S2 peptide pools were significantly increased after a third vaccine compared to 6 months after a first dose, with significant increases in proliferative CD4+ and CD8+ T-cell responses to SARS-CoV-2 S1 and S2 after boosting. Responses to Alpha, Beta, Gamma, and Delta variants were boosted, although to a lesser extent for Omicron.

Conclusions

In PWH receiving a third vaccine dose, there were significant increases in B- and T-cell immunity, including to known variants of concern (VOCs).

Touizer E. et al.

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

Cell, December 2022; /doi.org/10.1016/j.isci.2022.105862

Abstract

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

Riddell A.C. et al.

Generation of Novel Severe Acute Respiratory Syndrome Coronavirus 2 Variants on the B.1.1.7 Lineage in 3 Patients With Advanced Human Immunodeficiency Virus-1 Disease

CID, December 2022 ; doi.org/10.1093/cid/ciac409 

Abstract

The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is of public health concern in case of vaccine escape. Described are 3 patients with advanced human immunodeficiency virus (HIV)-1 and chronic SARS-CoV-2 infection in whom there is evidence of selection and persistence of novel mutations that are associated with increased transmissibility and immune escape.

Benet S et al.

Limited Humoral and Specific T-Cell Responses After SARS-CoV-2 Vaccination in PWH With Poor Immune Reconstitution

The Journal of Infectious Diseases, October 2022; doi.org/10.1093/infdis/jiac406

Abstract

Background

We analyzed humoral and cellular immune responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in people with human immunodeficiency virus (HIV; PWH) who had CD4+ T-cell counts <200/µL (HIV<200 group).

Conclusions

One-third of PWH with CD4+ T-cell counts <200/µL show low anti-S/anti-RBD IgG levels, reduced in vitro neutralization activity against SARS-CoV-2, and no vaccine-induced T cells after receiving coronavirus disease 2019 mRNA vaccines.

Auerbach J.D. et al

Living with COVID-19 and preparing for future pandemics: revisiting lessons from the HIV pandemic

The Lancet, November 2022; doi.org/10.1016/S2352-3018(22)00301-0

Abstract

Summary In April, 2020, just months into the COVID-19 pandemic, an international group of public health researchers published three lessons learned from the HIV pandemic for the response to COVID-19, which were to: anticipate health inequalities, create an enabling environment to support behavioural change, and engage a multidisciplinary effort. We revisit these lessons in light of more than 2 years’ experience with the COVID-19 pandemic. With specific examples, we detail how inequalities have played out within and between countries, highlight factors that support or impede the creation of enabling environments, and note ongoing issues with the scarcity of integrated science and health system approaches. We argue that to better apply lessons learned as the COVID19 pandemic matures and other infectious disease outbreaks emerge, it will be imperative to create dialogue among polarised perspectives, identify shared priorities, and draw on multidisciplinary evidence.

Murphy E. et al.

Innovations, adaptations, and accelerations in the delivery of HIV services during COVID-19

Lancet, October 2022;doi.org/10.1016/S2352-3018(22)00268-5

Abstract

To mitigate the negative consequences of the COVID-19 pandemic, service providers and communities adapted and accelerated an array of HIV interventions to meet the needs of people living with HIV and people at risk of acquiring HIV in diverse geographical and epidemiological settings.

R.L. Miller et al.

Impact of SARS-CoV-2 lockdown on expansion of HIV transmission clusters among key populations: a retrospective phylogenetic analysis

The Lancet Regional Health – Americas, September 2022; doi.org/10.1016/j. lana.2022.100369

Abstract

Public health measures designed to reduce SARS-CoV-2 transmission led to reduced access to care and prevention services for people living with or at risk of acquiring HIV, particularly during the initial introduction of extensive restrictions. This reduction in access may have contributed to increases in HIV transmission not outweighed by decreases in transmission occurring as a result of reduced contact rates promoted by the same public health measures.

A. Vergori et al.

Immunogenicity to COVID-19 mRNA vaccine third dose in people living with HIV

Nature Communications, August 2022; doi: 10.1038/s41467-022-32263-7

Abstract

In order to investigate safety and immunogenicity of SARS-CoV-2 vaccine third dose in people living with HIV (PLWH), we analyze anti-RBD, microneutralization assay and IFN-γ production in 216 PLWH on ART with advanced disease (CD4 count <200 cell/mm3 and/or previous AIDS) receiving the third dose of a mRNA vaccine (BNT162b2 or mRNA-1273) after a median of 142 days from the second dose. Median age is 54 years, median CD4 nadir 45 cell/mm3 (20-122), 93% HIV-RNA < 50 c/mL. In 68% of PLWH at least one side-effect, generally mild, is recorded. Humoral response after the third dose was strong and higher than that achieved with the second dose (>2 log2 difference), especially when a heterologous combination with mRNA-1273 as third shot is used. In contrast, cell-mediated immunity remain stable. Our data support usefulness of third dose in PLWH currently receiving suppressive ART who presented with severe immune dysregulation.

T. Calder et al.

Leveraging lessons learned from the COVID-19 pandemic for HIV

Communications Medicine, August 2022; doi: 10.1038/s43856-022-00175-8

Abstract

The rapid development of COVID-19 vaccines and their deployment in less than a year is an unprecedented scientific, medical, and public health achievement. This rapid development leveraged knowledge from decades of HIV/AIDS research and advances. However, the search for an HIV vaccine that would contribute to a durable end to the HIV pandemic remains elusive. Here, we draw from the US government experience and highlight lessons learned from COVID-19 vaccine development, which include the importance of public-private partnerships, equitable inclusion of populations impacted by the infectious pathogen, and continued investment in basic research. We summarize key considerations for an accelerated and re-energized framework for developing a safe and efficacious HIV vaccine.

Bertagnolio et al.

Clinical features of, and risk factors for, severe or fatal COVID-19 among people living with HIV admitted to hospital: analysis of data from the WHO Global Clinical Platform of COVID-19

Lancet HIV, May 2022; doi.org/10.1016/ S2352-3018(22)00097-2

Abstract

Background WHO has established a Global Clinical Platform for the clinical characterisation of COVID-19 among hospitalised individuals. We assessed whether people living with HIV hospitalised with COVID-19 had increased odds of severe presentation and of in-hospital mortality compared with individuals who were HIV-negative and associated risk factors.

Methods Between Jan 1, 2020, and July 1, 2021, anonymised individual-level data from 338 566 patients in 38 countries were reported to WHO. Using the Platform pooled dataset, we performed descriptive statistics and regression analyses to compare outcomes in the two populations and identify risk factors.

Findings Of 197479 patients reporting HIV status, 16955 (8·6%) were people living with HIV. 16283 (96.0%) of the 16 955 people living with HIV were from Africa; 10603 (62·9%) were female and 6271 (37·1%) were male; the mean age was 45·5 years (SD 13·7); 6339 (38·3%) were admitted to hospital with severe illness; and 3913 (24·3%) died in hospital. Of the 10166 people living with HIV with known antiretroviral therapy (ART) status, 9302 (91·5%) were on ART. Compared with individuals without HIV, people living with HIV had 15% increased odds of severe presentation with COVID-19 (aOR 1·15, 95% CI 1·10–1·20) and were 38% more likely to die in hospital (aHR 1·38, 1·34–1·41). Among people living with HIV, male sex, age 45–75 years, and having chronic cardiac disease or hypertension increased the odds of severe COVID-19; male sex, age older than 18 years, having diabetes, hypertension, malignancy, tuberculosis, or chronic kidney disease increased the risk of in-hospital mortality. The use of ART or viral load suppression were associated with a reduced risk of poor outcomes; however, HIV infection remained a risk factor for severity and mortality regardless of ART and viral load suppression status.

Interpretation In this sample of hospitalised people contributing data to the WHO Global Clinical Platform for COVID-19, HIV was an independent risk factor for both severe COVID-19 at admission and in-hospital mortality. These findings have informed WHO immunisation policy that prioritises vaccination for people living with HIV. As the results mostly reflect the data contribution from Africa, this analysis will be updated as more data from other regions become available.

Feldman et al.

A collision of pandemics: HIV and COVID-19

Lancet HIV, May 2022; doi.org/10.1016/ S2352-3018(22)00132-1

Abstract

From the beginning of the pandemic, serious concerns were raised that COVID-19 might be associated with more severe disease and worse outcomes in people living with HIV. These concerns were not unfounded, given that respiratory viral infections are common, and might be more severe, in people living with HIV. Influenza, for example, leads to mortality rates up to 20-times greater in people with HIV, compared with those without HIV.1 Data regarding the outcomes of COVID-19 in people living with HIV have been conflicting. Initial matched case-control studies from the UK,2 USA,3 and South Africa4 showed no difference in disease severity and outcomes, including need for intensive care unit admission and death, compared with people who were HIV-negative, especially when adjusting for potential confounding demographic, clinical, and laboratory parameters.3,4 In contrast, large-scale population-based data from South Africa have shown an association between COVID-19 mortality and HIV status.

Corey L et al

Expanding Efforts and Support to Respond to the HIV and COVID-19 Intersecting Pandemics

JAMA, https://jamanetwork.com/journals/jama/fullarticle/2790239

CONTENUTO E COMMENTO : Interessante discussione sulla importanza del supporto a una risposta alla pandemia di HIV/AIDS, in particolare in termini di inclusione di tutte le persone in un percorso di cura, anche durante la pandemia di COVID-19.

Meiring S et al.

COVID-19 shedding study group. Prolonged shedding of SARS-CoV-2 at high viral loads amongst hospitalised immunocompromised persons living with HIV, South Africa

Clin Infect Dis.,

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac077/6520530?login=true

CONTENUTO E COMMENTO : In questo studio multicentrico condotto in Sud Africa in epoca pre-vaccinale, pubblicato sulla prestigiosa rivista « Clinical Infectious Diseases », viene valutata la capacità di shedding del virus SARS-CoV-2 in persone con infezione da HIV. Sono stati arruolati 300 pazienti ricoverati per COVID-19 (102 affetti da infezione da HIV e 155 non affetti da infezione da HIV), seguiti con tampone nasofaringeo/orofaringeo molecolare ogni 2 giorni, fino a negativizzazione di almeno due tamponi consecutivi. Dallo studio emerge un tempo mediano di negativizzazione del tampone di 13 giorni e non sono state riscontrate differenze significative fra pazienti con infezione da HIV o meno. In un subset di pazienti con alte cariche virali iniziali viene tuttavia riscontrato uno shedding virale ad alta carica significativamente più prolungato nei pazienti con infezione da HIV e conta dei CD4 <200 cellule/mm3 rispetto a pazienti non infetti da HIV (tempo mediano di 27 giorni vs 7 giorni), con risultati simili in pazienti con viremia HIV non soppressa rispetto a pazienti non infetti da HIV.

Sebbene lo shedding virale non sembrerebbe essere influenzato dalla coinfezione con HIV, dai risultati di questo lavoro sembrerebbe emergere che i pazienti HIV con scarso controllo viro-immunologico presenterebbero uno shedding virale ad alta carica più prolungato. Pertanto, tali risultati ribadiscono l’importanza di una precoce diagnosi e trattamento di infezione da HIV, al fine di migliorare non solo lo stato di salute del singolo paziente, ma anche al fine di minimizzare la diffusione del virus SARS-CoV-2 nella popolazione generale.

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