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.

Lee MJ et al

Clinical outcomes of patients with and without HIV hospitalized with COVID- 19 in England during the early stages of the pandemic: a matched retrospective multi- centre analysis (RECEDE- C19 study)

HIV Medicine, https://onlinelibrary.wiley.com/doi/epdf/10.1111/hiv.13174

CONTENUTO : Studio retrospettivo multicentrico matched di coorte condotto in Inghilterra, in cui sono stati inclusi pazienti con infezione da SARS-CoV-2 ricoverati tra febbraio e maggio 2020 e analizzati in base allo stato sierologico di HIV. All’analisi univariata i pazienti con infezione da HIV (PLWH) avevano un rischio minore di miglioramento clinico o di dimissione al giorno 28 rispetto ai pazienti HIV-negativi. Tuttavia, ad una successiva analisi corretta per fattori confondenti quali comorbidità, etnia, fragilità ed altri fattori demografici, questa differenza di rischio perdeva di significatività statistica. Questo lavoro dimostra l’importanza nell’individuare un adeguato gruppo di controllo quando si tenta di studiare gli outcome dei PLWH ricoverati per COVID-19.

COMMENTO: l’impatto di HIV su COVID-19 è stato oggetto di numerosi studi fin dagli inizi della pandemia. Non sempre i risultati ottenuti sono stati univoci. In alcuni casi HIV risultava un elemento peggiorativo in altri indifferente o addirittura protettivo. Una possibile spiegazione di ciò potrebbe risiedere, come ipotizzato in questo lavoro, su aspetti di natura metodologica.

 Melanie Stecher M. et al.

Treatment modifcation after starting cART in people living with HIV: retrospective analysis of the German ClinSurv. HIV Cohort 2005–2017

Infection, July 2020; doi.org/10.1007/s15010-020-01469-6

Nachega SB et al

Scaling Up Covid-19 Vaccination in Africa — Lessons from the HIV Pandemic

NEJM, July 2021;  DOI: 10.1056/NEJMp2103313

COMMENTO: As we have learned from the HIV pandemic, biomedical advances alone are insufficient to sustainably control a pandemic. Considerations related to health infrastructure, local epidemiology, and responsiveness to local concerns and beliefs are critical for ending the Covid-19 pandemic — not only in Africa, but also globally. Each country will have its own unique challenges in vaccine distribution, which should be addressed with careful planning, including leveraging computational models of prioritization and rollout strategies, and applying methods from implementation science to maximize local impact. Addressing these differences is essential if we are to control current and future pandemics.

Shinde V et al

Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant

NEJM, May 2021 ; DOI: 10.1056/NEJMoa2103055

COMMENTO: BACKGROUND : The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the coronavirus disease 2019 (Covid-19) pandemic. In a phase 1–2 trial involving healthy adults, the NVX-CoV2373 nanoparticle vaccine had an acceptable safety profile and was associated with strong neutralizing-antibody and antigen-specific polyfunctional CD4+ T-cell responses. Evaluation of vaccine efficacy was needed in a setting of ongoing SARS-CoV-2 transmission.

METHODS : In this phase 2a–b trial in South Africa, we randomly assigned human immunodeficiency virus (HIV)–negative adults between the ages of 18 and 84 years or medically stable HIV-positive participants between the ages of 18 and 64 years in a 1:1 ratio to receive two doses of either the NVX-CoV2373 vaccine (5 μg of recombinant spike protein with 50 μg of Matrix-M1 adjuvant) or placebo. The primary end points were safety and vaccine efficacy against laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants without previous SARS-CoV-2 infection.

RESULTS : Of 6324 participants who underwent screening, 4387 received at least one injection of vaccine or placebo. Approximately 30% of the participants were seropositive for SARS-CoV-2 at baseline. Among 2684 baseline seronegative participants (94% HIV-negative and 6% HIV-positive), predominantly mild-to-moderate Covid-19 developed in 15 participants in the vaccine group and in 29 in the placebo group (vaccine efficacy, 49.4%; 95% confidence interval [CI], 6.1 to 72.8). Vaccine efficacy among HIV-negative participants was 60.1% (95% CI, 19.9 to 80.1). Of 41 sequenced isolates, 38 (92.7%) were the B.1.351 variant. Post hoc vaccine efficacy against B.1.351 was 51.0% (95% CI, −0.6 to 76.2) among the HIV-negative participants. Preliminary local and systemic reactogenicity events were more common in the vaccine group; serious adverse events were rare in both groups.

CONCLUSIONS : The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, with higher vaccine efficacy observed among HIV-negative participants. Most infections were caused by the B.1.351 variant.

Stanford KA et al

Incorporating HIV Screening With COVID-19 Testing in an Urban Emergency Department During the Pandemic

JAMA, April 2021;  doi:10.1001/jamainternmed.2021.0839

COMMENTO: Most sites experienced significant reductions in HIV screens during the pandemic, and overall, the program saw a 49% reduction in testing events from January 1 to April 30, 2020. The ED at UCM, however, maintained HIV screening volumes throughout the pandemic (Figure) and performed 19 111 HIV screens (14 215 in the ED) between January 1 and October 16, 2020, along with 112 242 COVID-19 polymerase chain reaction (PCR) tests (18 830 in the ED). Twelve patients were diagnosed with AHI after the first COVID-19 diagnosis in Cook County on January 24, 2020 (Table). The rate of AHI diagnoses per day was significantly higher during the pandemic compared with the prior 4 years (incidence rate ratio, 2.43; 95% CI, 1.22-4.83; P = .01). Other EDs not incorporating HIV screening into COVID-19 testing saw a 25% decrease in AHI diagnoses (incidence rate ratio, 0.75; 95% CI, 0.26-2.14; P = .59) that was not statistically significant.

Patients with AHI comprised 12 of 46 (26.1%) new diagnoses at UCM, the highest proportion on record. Included were 9 men (6 men who have sex with men, 2 heterosexual, and 1 undisclosed) and 3 cisgender women with a median (range) age of 25 (21-28) years. The median (range) viral load was 6 million (115 000 to >6 million) copies/mL. Eleven of 12 patients presented with symptoms consistent with COVID-19. One patient had COVID-19 infection and AHI. All were linked and initiated antiretroviral therapy by a median (range) of 1 (0-38) day from the time of PCR result but 3 (1-41) days from sample collection owing to delays in reflex PCR confirmatory testing, a result of high demands on laboratory personnel and scarcity of supplies (eg, amplification and testing trays) owing to COVID-19 testing volumes.

Laracy J et al

HIV-1 Infection Does Not Change Disease Course or Inflammatory Pattern of SARS-CoV-2-Infected Patients Presenting at a Large Urban Medical Center in New York City

Open Forum Infectious Diseases, February 2021; doi.org/10.1093/ofid/ofab029

COMMENTO: Background: The clinical impact of coronavirus disease 2019 (COVID-19) among people with HIV (PWH) remains unclear. In this retrospective cohort study of COVID-19, we compared clinical outcomes and laboratory parameters among PWH and controls. Methods: Sixty-eight PWH diagnosed with COVID-19 were matched 1:4 to patients without known HIV diagnosis, drawn from a study population of all patients who were diagnosed with COVID-19 at an academic urban hospital. The primary outcome was death/discharge to hospice within 30 days of hospital presentation. Results: PWH were more likely to be admitted from the emergency department than patients without HIV (91% vs 71%; P = .001). We observed no statistically significant difference between admitted PWH and patients without HIV in terms of 30-day mortality rate (19% vs 13%, respectively) or mechanical ventilation rate (18% vs 20%, respectively). PWH had higher erythrocyte sedimentation rates than controls on admission but did not differ in other inflammatory marker levels or nasopharyngeal/oropharyngeal severe acute respiratory syndrome coronavirus 2 viral load estimated by reverse transcriptase polymerase chain reaction cycle thresholds. Conclusions: HIV infection status was associated with a higher admission rate; however, among hospitalized patients, PWH did not differ from HIV-uninfected controls by rate of mechanical ventilation or death/discharge to hospice.

Tesoriero JM et al

COVID-19 Outcomes Among Persons Living With or Without Diagnosed HIV Infection in New York State

JAMA, Febrary 2021; DOI: 10.1001/jamanetworkopen.2020.37069

COMMENTO: Importance  New York State has been an epicenter for both the US coronavirus disease 2019 (COVID-19) and HIV/AIDS epidemics. Persons living with diagnosed HIV may be more prone to COVID-19 infection and severe outcomes, yet few studies have assessed this possibility at a population level.

Objective  To evaluate the association between HIV diagnosis and COVID-19 diagnosis, hospitalization, and in-hospital death in New York State.

Design, Setting, and Participants  This cohort study, conducted in New York State, including New York City, between March 1 and June 15, 2020, matched data from HIV surveillance, COVID-19 laboratory-confirmed diagnoses, and hospitalization databases to provide a full population-level comparison of COVID-19 outcomes between persons living with diagnosed HIV and persons living without diagnosed HIV.

Exposures  Diagnosis of HIV infection through December 31, 2019.

Main Outcomes and Measures  The main outcomes were COVID-19 diagnosis, hospitalization, and in-hospital death. COVID-19 diagnoses, hospitalizations, and in-hospital death rates comparing persons living with diagnosed HIV with persons living without dianosed HIV were computed, with unadjusted rate ratios and indirect standardized rate ratios (sRR), adjusting for sex, age, and region. Adjusted rate ratios (aRRs) for outcomes specific to persons living with diagnosed HIV were assessed by age, sex, region, race/ethnicity, transmission risk, and CD4+ T-cell count–defined HIV disease stage, using Poisson regression models.

Results  A total of 2988 persons living with diagnosed HIV (2109 men [70.6%]; 2409 living in New York City [80.6%]; mean [SD] age, 54.0 [13.3] years) received a diagnosis of COVID-19. Of these persons living with diagnosed HIV, 896 were hospitalized and 207 died in the hospital through June 15, 2020. After standardization, persons living with diagnosed HIV and persons living without diagnosed HIV had similar diagnosis rates (sRR, 0.94 [95% CI, 0.91-0.97]), but persons living with diagnosed HIV were hospitalized more than persons living without diagnosed HIV, per population (sRR, 1.38 [95% CI, 1.29-1.47]) and among those diagnosed (sRR, 1.47 [95% CI, 1.37-1.56]). Elevated mortality among persons living with diagnosed HIV was observed per population (sRR, 1.23 [95% CI, 1.07-1.40]) and among those diagnosed (sRR, 1.30 [95% CI, 1.13-1.48]) but not among those hospitalized (sRR, 0.96 [95% CI, 0.83-1.09]). Among persons living with diagnosed HIV, non-Hispanic Black individuals (aRR, 1.59 [95% CI, 1.40-1.81]) and Hispanic individuals (aRR, 2.08 [95% CI, 1.83-2.37]) were more likely to receive a diagnosis of COVID-19 than White individuals, but they were not more likely to be hospitalized once they received a diagnosis or to die once hospitalized. Hospitalization risk increased with disease progression to HIV stage 2 (aRR, 1.29 [95% CI, 1.11-1.49]) and stage 3 (aRR, 1.69 [95% CI, 1.38-2.07]) relative to stage 1.

Conclusions and Relevance  In this cohort study, persons living with diagnosed HIV experienced poorer COVID-related outcomes relative to persons living without diagnosed HIV; Previous HIV diagnosis was associated with higher rates of severe disease requiring hospitalization, and hospitalization risk increased with progression of HIV disease stage.

Ceballos ME et al

Clinical characteristics and outcomes of people living with HIV hospitalized with COVID-19: a nationwide experience

International Journal of STD & AIDS, Febrary 2021; DOI: 10.1177/0956462420973106

COMMENTO : In this prospective, multicentric, observational study, we describe the clinical characteristics and outcomes of people living with HIV (PLHIV) requiring hospitalization due to COVID-19 in Chile and compare them with Chilean general population admitted with SARS-CoV-2. Consecutive PLHIV admitted with COVID-19 in 23 hospitals, between 16 April and 23 June 2020, were included. Data of a temporally matched-hospitalized general population were used to compare demography, comorbidities, COVID-19 symptoms, and major outcomes. In total, 36 PLHIV subjects were enrolled; 92% were male and mean age was 44 years. Most patients (83%) were on antiretroviral therapy; mean CD4 count was 557 cells/mm3. Suppressed HIV viremia was found in 68% and 56% had, at least, one comorbidity. Severe COVID-19 occurred in 44.4%, intensive care was required in 22.2%, and five patients died (13.9%). No differences were seen between recovered and deceased patients in CD4 count, HIV viral load, or time since HIV diagnosis. Hypertension and cardiovascular disease were associated with a higher risk of death (p = 0.02 and 0.006, respectively). Compared with general population, the HIV cohort had significantly more men (OR 0.15; IC 95% 0.07–0.31) and younger age (OR 8.68; IC 95% 2.66–28.31). In PLHIV, we found more intensive care unit admission (OR 2.31; IC 95% 1.05–5.07) but no differences in the need for mechanical ventilation or death. In this cohort of PLHIV hospitalized with COVID-19, hypertension and cardiovascular comorbidities, but not current HIV viro-immunologic status, were the most important risk factors for mortality. No differences were found between PLHIV and general population in the need for mechanical ventilation and death.

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