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1.
PLoS One ; 17(7): e0270770, 2022.
Article in English | MEDLINE | ID: covidwho-2039352

ABSTRACT

BACKGROUND: The risk and characteristics of upper respiratory tract (URT) bacterial infections (URT-BI) among HIV (+) patients is understudied. We analyzed factors associated with its occurrence and the spectrum of culturable pathogens among patients routinely followed at the HIV Out-Patient Clinic in Warsaw. METHODS: All HIV (+) patients with available URT swab culture were included into analyses. Patients were followed from the day of registration in the clinic until first positive URT swab culture or last clinical visit from January 1, 2007 to July 31, 2016. Cox proportional hazard models were used to identify factors associated with positive URT swabs culture (those with p<0.1 in univariate included into multivariable). RESULTS: In total 474 patients were included into the analyses, 166 with culturable URT swab. In general, 416 (87.8%) patients were male, 342 (72.1%) were infected through MSM contact, 253 (53.4%) were on antiretroviral therapy. Median follow-up time was 3.4 (1.3-5.7) years, age 35.2 (30.6-42.6) years and CD4+ count 528 (400-685) cells/µl. The most common cultured bacteria were S. aureus (40.4%) and S. pyogenes (13.9%) (Table 1). Patients with culturable URT-BI were more likely to be MSM (68.5% vs 78.9%; p<0.016), have detectable viral load (20.9% vs 12.0%; p<0.0001) and CD4+ cell count <500 cells/µl (55.2% vs 39.0%; p = 0.003) (Table 2). In multivariate survival analyses detectable viral load (HR3.13; 95%Cl: 2.34-4.19) and MSM (1.63;1.09-2.42) were increasing, but older age (0.63;0.58-0.69, per 5 years older) and higher CD4+ count (0.90;0.85-0.95, per 100 cells/µl) decreasing the risk of culturable URT-BI (Table 2). CONCLUSIONS: Culturable URT-BI are common among HIV-positive patients with high CD4+ count. Similarly to general population most common cultured bacteria were S. aureus and S. pyogenes. Risk factors identified in multivariate survival analysis indicate that younger MSM patients with detectable HIV viral load are at highest risk. In clinical practice this group of patients requires special attention.


Subject(s)
Bacterial Infections , HIV Infections , Respiratory Tract Infections , Sexual and Gender Minorities , Adult , Antiretroviral Therapy, Highly Active , Bacteria , Bacterial Infections/complications , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , CD4 Lymphocyte Count , Female , HIV Infections/drug therapy , Homosexuality, Male , Humans , Male , Reinfection , Respiratory System , Respiratory Tract Infections/complications , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/epidemiology , Risk Factors , Staphylococcus aureus , Viral Load
2.
J Acquir Immune Defic Syndr ; 90(4): 369-376, 2022 08 01.
Article in English | MEDLINE | ID: covidwho-1909060

ABSTRACT

BACKGROUND: Understanding the spectrum of COVID-19 in people with HIV (PWH) is critical to provide clinical guidance and risk reduction strategies. SETTING: Centers for AIDS Research Network of Integrated Clinic System, a US multisite clinical cohort of PWH in care. METHODS: We identified COVID-19 cases and severity (hospitalization, intensive care, and death) in a large, diverse HIV cohort during March 1, 2020-December 31, 2020. We determined predictors and relative risks of hospitalization among PWH with COVID-19, adjusted for disease risk scores. RESULTS: Of 16,056 PWH in care, 649 were diagnosed with COVID-19 between March and December 2020. Case fatality was 2%; 106 (16.3%) were hospitalized, and 12 died. PWH with current CD4 count <350 cells/mm 3 [aRR 2.68; 95% confidence interval (CI): 1.93 to 3.71; P < 0.001] or lowest recorded CD4 count <200 cells/mm 3 (aRR 1.67; 95% CI: 1.18 to 2.36; P < 0.005) had greater risks of hospitalization. HIV viral load and antiretroviral therapy status were not associated with hospitalization, although most of the PWH were suppressed (86%). Black PWH were 51% more likely to be hospitalized with COVID-19 compared with other racial/ethnic groups (aRR 1.51; 95% CI: 1.04 to 2.19; P = 0.03). Chronic kidney disease, chronic obstructive pulmonary disease, diabetes, hypertension, obesity, and increased cardiovascular and hepatic fibrosis risk scores were associated with higher hospitalization risk. PWH who were older, not on antiretroviral therapy, and with current CD4 count <350 cells/mm 3 , diabetes, and chronic kidney disease were overrepresented among PWH who required intubation or died. CONCLUSIONS: PWH with CD4 count <350 cells/mm 3 , and a history of CD4 count <200 cells/mm 3 , have a clear excess risk of severe COVID-19, accounting for comorbidities associated with severe outcomes. PWH with these risk factors should be prioritized for COVID-19 vaccination and early treatment and monitored closely for worsening illness.


Subject(s)
COVID-19 , HIV Infections , Renal Insufficiency, Chronic , CD4 Lymphocyte Count , COVID-19/complications , COVID-19/epidemiology , COVID-19 Vaccines , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Renal Insufficiency, Chronic/complications , United States/epidemiology
3.
N Engl J Med ; 386(19): 1793-1803, 2022 05 12.
Article in English | MEDLINE | ID: covidwho-1895621

ABSTRACT

BACKGROUND: Patients with multidrug-resistant human immunodeficiency virus type 1 (HIV-1) infection have limited treatment options. Lenacapavir is a first-in-class capsid inhibitor that showed substantial antiviral activity in a phase 1b study. METHODS: In this phase 3 trial, we enrolled patients with multidrug-resistant HIV-1 infection in two cohorts, according to the change in the plasma HIV-1 RNA level between the screening and cohort-selection visits. In cohort 1, patients were first randomly assigned in a 2:1 ratio to receive oral lenacapavir or placebo in addition to their failing therapy for 14 days; during the maintenance period, starting on day 15, patients in the lenacapavir group received subcutaneous lenacapavir once every 6 months, and those in the placebo group received oral lenacapavir, followed by subcutaneous lenacapavir; both groups also received optimized background therapy. In cohort 2, all the patients received open-label oral lenacapavir with optimized background therapy on days 1 through 14; subcutaneous lenacapavir was then administered once every 6 months starting on day 15. The primary end point was the percentage of patients in cohort 1 who had a decrease of at least 0.5 log10 copies per milliliter in the viral load by day 15; a key secondary end point was a viral load of less than 50 copies per milliliter at week 26. RESULTS: A total of 72 patients were enrolled, with 36 in each cohort. In cohort 1, a decrease of at least 0.5 log10 copies per milliliter in the viral load by day 15 was observed in 21 of 24 patients (88%) in the lenacapavir group and in 2 of 12 patients (17%) in the placebo group (absolute difference, 71 percentage points; 95% confidence interval, 35 to 90). At week 26, a viral load of less than 50 copies per milliliter was reported in 81% of the patients in cohort 1 and in 83% in cohort 2, with a least-squares mean increase in the CD4+ count of 75 and 104 cells per cubic millimeter, respectively. No serious adverse events related to lenacapavir were identified. In both cohorts, lenacapavir-related capsid substitutions that were associated with decreased susceptibility developed in 8 patients during the maintenance period (6 with M66I substitutions). CONCLUSIONS: In patients with multidrug-resistant HIV-1 infection, those who received lenacapavir had a greater reduction from baseline in viral load than those who received placebo. (Funded by Gilead Sciences; CAPELLA ClinicalTrials.gov number, NCT04150068.).


Subject(s)
Anti-HIV Agents , Drug Resistance, Multiple, Viral , HIV Infections , HIV-1 , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , Capsid , Drug Therapy, Combination , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/drug effects , HIV-1/genetics , Humans , RNA, Viral , Viral Load
4.
Viruses ; 14(6)2022 06 03.
Article in English | MEDLINE | ID: covidwho-1884380

ABSTRACT

In South Africa, high exposure to SARS-CoV-2 occurs primarily in densely populated, low-income communities, which are additionally burdened by highly prevalent Human Immunodeficiency Virus (HIV). With the aim to assess SARS-CoV-2 seroprevalence and its association with HIV-related clinical parameters in non-hospitalized patients likely to be highly exposed to SARS-CoV-2, this observational cross-sectional study was conducted at the Gugulethu Community Health Centre Antiretroviral clinic between October 2020 and June 2021, after the first COVID-19 wave in South Africa and during the second and beginning of the third wave. A total of 150 adult (median age 39 years [range 20-65 years]) HIV-infected patients (69% female; 31% male) were recruited. 95.3% of the cohort was on antiretroviral therapy (ART), had a median CD4 count of 220 cells/µL (range 17-604 cells/µL) and a median HIV viral load (VL) of 49 copies/mL (range 1-1,050,867 copies/mL). Furthermore, 106 patients (70.7%) were SARS-CoV-2 seropositive, and 0% were vaccinated. When stratified for HIV VL, patients with uncontrolled HIV viremia (HIV VL > 1000 copies/mL) had significantly higher odds of SARS-CoV-2 seropositivity than patients with HIV VL < 1000 copies/mL, after adjusting for age, sex and ART status (p = 0.035, adjusted OR 2.961 [95% CI: 1.078-8.133]). Although the cause-effect relationship could not be determined due to the cross-sectional study design, these results point towards a higher risk of SARS-CoV-2 susceptibility among viremic HIV patients, or impaired HIV viral control due to previous co-infection with SARS-CoV-2.


Subject(s)
COVID-19 , HIV Infections , Adult , Aged , CD4 Lymphocyte Count , COVID-19/epidemiology , Cross-Sectional Studies , Female , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Male , Middle Aged , SARS-CoV-2 , Seroepidemiologic Studies , South Africa/epidemiology , Viral Load , Viremia/drug therapy , Viremia/epidemiology , Young Adult
6.
Pediatr Infect Dis J ; 41(5): e208-e215, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-1831448

ABSTRACT

BACKGROUND: Bacterial pneumonia imparts a major morbidity and mortality burden on children living with HIV, yet effective prevention and treatment options are underutilized. We explored clinical factors associated with severe recurrent bacterial pneumonia among children living with HIV. METHODS: Children enrolled in the TREAT Asia Pediatric HIV Observational Database were included if they started antiretroviral therapy (ART) on or after January 1st, 2008. Factors associated with severe recurrent bacterial pneumonia were assessed using competing-risk regression. RESULTS: A total of 3,944 children were included in the analysis; 136 cases of severe recurrent bacterial pneumonia were reported at a rate of 6.5 [95% confidence interval (CI): 5.5-7.7] events per 1,000 patient-years. Clinical factors associated with severe recurrent bacterial pneumonia were younger age [adjusted subdistribution hazard ratio (aHR): 4.4 for <5 years versus ≥10 years, 95% CI: 2.2-8.4, P < 0.001], lower weight-for-age z-score (aHR: 1.5 for <-3.0 versus >-2.0, 95% CI: 1.1-2.3, P = 0.024), pre-ART diagnosis of severe recurrent bacterial pneumonia (aHR: 4.0 versus no pre-ART diagnosis, 95% CI: 2.7-5.8, P < 0.001), past diagnosis of symptomatic lymphoid interstitial pneumonitis or chronic HIV-associated lung disease, including bronchiectasis (aHR: 4.8 versus no past diagnosis, 95% CI: 2.8-8.4, P < 0.001), low CD4% (aHR: 3.5 for <10% versus ≥25%, 95% CI: 1.9-6.4, P < 0.001) and detectable HIV viral load (aHR: 2.6 versus undetectable, 95% CI: 1.2-5.9, P = 0.018). CONCLUSIONS: Children <10-years-old and those with low weight-for-age, a history of respiratory illness, low CD4% or poorly controlled HIV are likely to gain the greatest benefit from targeted prevention and treatment programs to reduce the burden of bacterial pneumonia in children living with HIV.


Subject(s)
Anti-HIV Agents , HIV Infections , Pneumonia, Bacterial , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , Child , HIV Infections/drug therapy , Humans , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/epidemiology
7.
Clin Microbiol Infect ; 28(4): 570-579, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1828106

ABSTRACT

OBJECTIVES: To explore changes over time in the epidemiology of tuberculosis (TB) in Denmark in people living with human immunodeficiency virus (HIV) (PLWH). METHODS: In this nationwide, population-based cohort study we included all adult PLWH from the Danish HIV Cohort Study (1995-2017) without previous TB. We estimated TB incidence rate (IR), all-cause mortality rate (MR), associated risk and prognostic factors using Poisson regression. RESULTS: Among 6982 PLWH (73 596 person-years (PY)), we observed 217 TB events (IR 2.9/1000 PY, 95% CI 2.6-3.4: IR 6.7, 95% CI 5.7-7.9 among migrants and IR 1.4, 95% CI 1.1-1.7 among Danish-born individuals; p < 0.001). The IR of concomitant HIV/TB remained high and unchanged over time. The IR of TB diagnosed >3 months after HIV diagnosis declined with calendar time, longer time from HIV diagnosis, and CD4 cell recovery. Independent TB risk factors were African/Asian/Greenland origin (adjusted incidence rate ratio (aIRR) 5.2, 95% CI 3.5-7.6, aIRR 6.5, 95% CI 4.2-10.0, aIRR 7.0, 95% CI 3.4-14.6, respectively), illicit drug use (aIRR 6.9, 95% CI 4.2-11.2), CD4 <200 cells/µL (aIRR 2.7, 95% CI 2.0-3.6) and not receiving antiretroviral therapy (aIRR 3.7, 95% CI 2.5-5.3). Fifty-five patients died (MR 27.9/1000 PY, 95% CI 21.4-36.3), with no improvement in mortality over time. Mortality prognostic factors were Danish-origin (adjusted mortality rate ratio (aMRR) 2.3, 95% CI 1.3-4.3), social burden (aMRR 3.9, 95% CI 2.2-7.0), CD4 <100 cells/µL at TB diagnosis (aMRR 2.6, 95% CI 1.3-4.9), TB diagnosed >3 months after HIV versus concomitant diagnosis (aMRR 4.3, 95% CI 2.2-8.7) and disseminated TB (aMRR 3.3, 95% CI 1.1-9.9). CONCLUSION: Late HIV presentation with concomitant TB remains a challenge. Declining TB rates in PLWH were observed over time and with CD4 recovery, highlighting the importance of early and successful antiretroviral therapy. However, MR remained high. Our findings highlight the importance of HIV and TB screening strategies and treatment of latent TB in high-risk groups.


Subject(s)
HIV Infections , Tuberculosis , Adult , CD4 Lymphocyte Count , Cohort Studies , Denmark/epidemiology , HIV , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Incidence , Risk Factors , Tuberculosis/complications , Tuberculosis/drug therapy , Tuberculosis/epidemiology
8.
Viruses ; 14(5)2022 05 05.
Article in English | MEDLINE | ID: covidwho-1820424

ABSTRACT

HIV-positive patients may present lungs with multiple infections, which may hinder differential diagnoses and the choice of treatment in the course of COVID-19, especially in countries with limited access to high-standard healthcare. Here, we aim to investigate the association between radiological changes and poor COVID-19 outcomes among HIV-positive patients from Central and Eastern Europe. Between November 2020 and May 2021, the Euroguidelines in Central and Eastern Europe Network Group started collecting observational data on HIV and COVID-19 co-infections. In total, 16 countries from Central and Eastern European submitted data (eCRF) on 557 HIV-positive patients. The current analyses included patients who had a radiological examination performed. Logistic regression models were used to identify the factors associated with death, ICU admission, and partial recovery (poor COVID-19 outcomes). Factors that were significant in the univariate models (p < 0.1) were included in the multivariate model. Radiological data were available for 224 (40.2%) patients, 108 (48.2%) had computed tomography, and 116 (51.8%) had a chest X-ray. Of these, 211 (94.2%) were diagnosed using RT-PCR tests, 212 (94.6%) were symptomatic, 123 (55.6%) were hospitalized, 37 (16.6%) required oxygen therapy, and 28 (13.1%) either died, were admitted to ICU, or only partially recovered. From the radiologist's description, 138 (61.6%) patients had typical radiological changes, 18 (8.0%) atypical changes, and 68 (30.4%) no changes. In the univariate models, CD4 count (OR = 0.86 [95% CI: 0.76-0.98]), having a comorbidity (2.33 [1.43-3.80]), HCV and/or HBV co-infection (3.17 [1.32-7.60]), being currently employed (0.31 [0.13-0.70]), being on antiretroviral therapy (0.22 [0.08-0.63]), and having typical (3.90 [1.12-13.65]) or atypical (10.8 [2.23-52.5]) radiological changes were all significantly associated with poor COVID-19 outcomes. In the multivariate model, being on antiretroviral therapy (OR = 0.20 [95% CI:0.05-0.80]) decreased the odds of poor COVID-19 outcomes, while having a comorbidity (2.12 [1.20-3.72]) or either typical (4.23 [1.05-17.0]) or atypical (6.39 [1.03-39.7]) radiological changes (vs. no changes) increased the odds of poor COVID-19 outcomes. Among HIV patients diagnosed with symptomatic SARS-CoV-2 infection, the presence of either typical or atypical radiological COVID-19 changes independently predicted poorer outcomes.


Subject(s)
COVID-19 , HIV Infections , CD4 Lymphocyte Count , COVID-19/epidemiology , Europe, Eastern , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , SARS-CoV-2
9.
Front Immunol ; 12: 794638, 2021.
Article in English | MEDLINE | ID: covidwho-1731769

ABSTRACT

CCR5 plays a central role in infectious disease, host defense, and cancer progression, thereby making it an ideal target for therapeutic development. Notably, CCR5 is the major HIV entry co-receptor, where its surface density correlates with HIV plasma viremia. The level of CCR5 receptor occupancy (RO) achieved by a CCR5-targeting therapeutic is therefore a critical predictor of its efficacy. However, current methods to measure CCR5 RO lack sensitivity, resulting in high background and overcalculation. Here, we report on two independent, flow cytometric methods of calculating CCR5 RO using the anti-CCR5 antibody, Leronlimab. We show that both methods led to comparable CCR5 RO values, with low background on untreated CCR5+CD4+ T cells and sensitive measurements of occupancy on both blood and tissue-resident CD4+ T cells that correlated longitudinally with plasma concentrations in Leronlimab-treated macaques. Using these assays, we found that Leronlimab stabilized cell surface CCR5, leading to an increase in the levels of circulating and tissue-resident CCR5+CD4+ T cells in vivo in Leronlimab-treated macaques. Weekly Leronlimab treatment in a chronically SIV-infected macaque led to increased CCR5+CD4+ T cells levels and fully suppressed plasma viremia, both concomitant with full CCR5 RO on peripheral blood CD4+ T cells, demonstrating that CCR5+CD4+ T cells were protected from viral replication by Leronlimab binding. Finally, we extended these results to Leronlimab-treated humans and found that weekly 700 mg Leronlimab led to complete CCR5 RO on peripheral blood CD4+ T cells and a statistically significant increase in CCR5+CD4+ T cells in peripheral blood. Collectively, these results establish two RO calculation methods for longitudinal monitoring of anti-CCR5 therapeutic antibody blockade efficacy in both macaques and humans, demonstrate that CCR5+CD4+ T cell levels temporarily increase with Leronlimab treatment, and facilitate future detailed investigations into the immunological impacts of CCR5 inhibition in multiple pathophysiological processes.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , CD4-Positive T-Lymphocytes/immunology , COVID-19/drug therapy , Flow Cytometry/methods , HIV Antibodies/therapeutic use , HIV Infections/drug therapy , HIV-1/physiology , Receptors, CCR5/metabolism , SARS-CoV-2/physiology , Simian Acquired Immunodeficiency Syndrome/drug therapy , Simian Immunodeficiency Virus/physiology , Animals , CD4 Lymphocyte Count , Female , Humans , Primates , Protein Binding , Receptors, CCR5/immunology , Treatment Outcome
10.
BMJ Open ; 12(2): e057291, 2022 Feb 07.
Article in English | MEDLINE | ID: covidwho-1723820

ABSTRACT

INTRODUCTION: Although the advanced HIV disease (AHD) care package reduces morbidity and mortality in people with AHD (defined in people living with HIV as WHO stage 3 or 4, CD4 count <200 cells/µL or age <5 years), it is barely implemented in many countries. A novel point-of-care CD4 test rapidly identifies AHD. We evaluate the feasibility of implementing the AHD care package as part of community-based HIV/tuberculosis services. METHODS AND ANALYSIS: This two-phased study is guided by the Medical Research Council framework for evaluation of complex interventions. Stage 1 is a stakeholder consultation to define tools and indicators to assess feasibility of the AHD care package. Stage 2 is the implementation of the AHD care package during a facility-based tuberculosis diagnostic accuracy study in high-burden HIV/tuberculosis settings. Consenting adults with tuberculosis symptoms in two sites in Lesotho and South Africa are eligible for inclusion. HIV-positive participants are included in the feasibility study and are offered a CD4 test, a tuberculosis-lipoarabinomannan assay and those with CD4 count of ≤200 cells/µL a cryptococcal antigen lateral flow assay. Participants are referred for clinical management following national guidelines. The evaluation includes group discussions, participant observation (qualitative strand) and a semistructured questionnaire to assess acceptability among implementers. The quantitative strand also evaluates process compliance (process rating and process cascade) and early outcomes (vital and treatment status after twelve weeks). Thematic content analysis, descriptive statistics and data triangulation will be performed. ETHICS AND DISSEMINATION: The National Health Research and Ethics Committee, Lesotho, the Human Sciences Research Council Research Ethics Committee and Provincial Department of Health, South Africa and the Ethikkommission Nordwest- und Zentralschweiz, Switzerland, approved the protocol. Dissemination will happen locally and internationally at scientific conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04666311.


Subject(s)
HIV Infections , Tuberculosis , Adult , CD4 Lymphocyte Count , Child, Preschool , Feasibility Studies , HIV Infections/drug therapy , Humans , Point-of-Care Systems , Tuberculosis/drug therapy , Tuberculosis/therapy
11.
AIDS Behav ; 26(7): 2256-2265, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1638712

ABSTRACT

People living with HIV (PLWH) are particularly vulnerable to worsened outcomes of COVID-19. Therefore, the purpose of this work was to provide a scoping review of the literature to assess the risk factors for COVID-19 mortality among PLWH. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR), searches were conducted in PubMed, Scopus, Global Health, and WHO Coronavirus Database. Articles were eligible for inclusion if they were in English, included PLWH who died after COVID-19 infection, and described risk factors for mortality. Results were descriptively synthesized and pooled thereafter. Study quality was assessed using the Joanna Brigg Institute's critical appraisal tools. 20 studies were eligible for inclusion, with the pooled death rate being 11.7%. Age was a major risk factor, especially after 50 (23.2%) and after 70 (41.8%), and males had a death rate nearly double that of females. As total comorbidities increased, the death rate also greatly increased; among those with comorbidities, the highest fatality rates were those with cardiovascular disease (30.2%), chronic kidney disease (23.5%), obesity (22.4%), and diabetes (18.4%). Other risk factors for mortality among PLWH included having a Black racial background, being an injection drug user, being a smoker, and having a CD4 cell count below 200. There is a need to better study confounding factors, and to understand how vaccination influences mortality risk. Overall, the findings highlight a need to ensure that focus is placed on the varying demographics of PLWH amidst COVID-19 control efforts.


Subject(s)
COVID-19 , HIV Infections , CD4 Lymphocyte Count , Female , HIV Infections/complications , Humans , Male , Risk Factors , SARS-CoV-2
12.
Sci Adv ; 8(3): eabj9815, 2022 Jan 21.
Article in English | MEDLINE | ID: covidwho-1634773

ABSTRACT

Safe and effective vaccines are needed to end the COVID-19 pandemic. Here, we report the preclinical development of a lipid nanoparticle­formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after the initial mouse vaccination results showed that it elicited the strongest neutralizing antibody response against SARS-CoV-2. Further tests in mice and hamsters indicated that PTX-COVID19-B induced robust humoral and cellular immune responses and completely protected the vaccinated animals from SARS-CoV-2 infection in the lung. Studies in hamsters also showed that PTX-COVID19-B protected the upper respiratory tract from SARS-CoV-2 infection. Mouse immune sera elicited by PTX-COVID19-B vaccination were able to neutralize SARS-CoV-2 variants of concern, including the Alpha, Beta, Gamma, and Delta lineages. No adverse effects were induced by PTX-COVID19-B in either mice or hamsters. Based on these results, PTX-COVID19-B was authorized by Health Canada to enter clinical trials in December 2020 with a phase 2 clinical trial ongoing.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Synthetic/immunology , /immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , CD4 Lymphocyte Count , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , COVID-19 Vaccines/adverse effects , Canada , Cell Line , Cricetinae , Drug Evaluation, Preclinical , Female , HEK293 Cells , Humans , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Liposomes/pharmacology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Nanoparticles , Spike Glycoprotein, Coronavirus/genetics , Th1 Cells/immunology
13.
J Acquir Immune Defic Syndr ; 89(1): 1-8, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1561815

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) symptoms among people living with HIV (PLWH) are not well described. SETTING: Longitudinal survey within the MACS/WIHS Combined Cohort Study (MWCCS) of PLWH compared with similar HIV-seronegative (SN) individuals. METHODS: Telephone-administered survey of MWCCS participants at 13 clinical research sites across the United States addressing COVID-19 symptoms, SARS-CoV-2 testing, and pandemic impact on social distancing and antiretroviral therapy (ART) use. Primary data collection occurred during May (wave 1), June-July (wave 2), and August-September, 2020 (wave 3). RESULTS: One-third of MWCCS participants were tested for SARS-CoV-2 infection; 10% was tested ≥2 times. Similar proportions of PLWH and SN participants were tested, but SARS-CoV-2 positivity was higher among PLWH than among SN individuals (9.4% vs 4.8%, P = 0.003). Odds of SARS-CoV-2 positivity remained higher among PLWH after adjusting for age, sex, race/ethnicity, and study site (adjusted odds ratio = 2.0, 95% confidence interval = 1.2 to 3.2). SARS-CoV-2 positivity was not associated with CD4 cell counts among PLWH. Among SARS-CoV-2 positive participants, 9% had no symptoms, 7% had 1-2 mild symptoms, and 84% had ≥3 symptoms. Most of the (98%) participants reported physical distancing during all survey waves; self-reported ART adherence among PLWH was not adversely affected during the pandemic compared with the previous year (similar adherence in 89% of participants, improved in 9% of participants, and decreased in 2% of participants). CONCLUSIONS: Despite similar SARS-CoV-2 testing and physical distancing profiles by HIV serostatus among MWCCS participants, PLWH who reported SARS-CoV-2 testing were more likely to have a positive test result. Additional studies are needed to determine whether and why PLWH are at increased risk of SARS-CoV-2 infection.


Subject(s)
COVID-19/diagnosis , Fever/etiology , HIV Infections/complications , Pharyngitis/etiology , SARS-CoV-2/isolation & purification , Aged , CD4 Lymphocyte Count , COVID-19/epidemiology , COVID-19 Testing , Cohort Studies , Cough , Ethnicity , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Longitudinal Studies , Male , Middle Aged , Prevalence
14.
S Afr Med J ; 111(12): 1174-1180, 2021 12 02.
Article in English | MEDLINE | ID: covidwho-1561763

ABSTRACT

BACKGROUND: The impact of SARS-CoV-2 infection in pregnant women living with HIV (PLHIV) has not been described previously. OBJECTIVES: To describe the clinical presentation and outcomes of a cohort of women with high-risk pregnancies with confirmed COVID-19 to determine whether risk factors for disease severity and adverse outcomes of COVID-19 differed in pregnant women without HIV compared with PLHIV. METHODS: We prospectively enrolled pregnant women with COVID-19 attending the high-risk obstetric service at Tygerberg Hospital, Cape Town, South Africa, from 1 May to 31 July 2020, with follow-up until 31 October 2020. Women were considered high risk if they required specialist care for maternal, neonatal and/or anaesthetic conditions. Common maternal or obstetric conditions included hypertensive disorders, morbid obesity (body mass index (BMI) ≥40 kg/m2) and diabetes. Information on demographics, clinical features, and maternal and neonatal outcomes was collected and compared for PLHIV v. pregnant women without HIV. RESULTS: One hundred women (72 without HIV and 28 PLHIV) with high-risk pregnancies had laboratory-confirmed COVID-19. Among the 28 PLHIV, the median (interquartile range) CD4 count was 441 (317 - 603) cells/µL, and 19/26 (73%) were virologically suppressed. COVID-19 was diagnosed predominantly in the third trimester (81%). Obesity (BMI ≥30 in n=61/81; 75%) and hypertensive disorders were frequent comorbidities. Of the 100 women, 40% developed severe or critical COVID-19, 15% required intensive care unit admission and 6% needed invasive ventilation. Eight women died, 1 from advanced HIV disease complicated by bacteraemia and urosepsis. The crude maternal mortality rate was substantially higher in women with COVID-19 compared with all other deliveries at our institution during this period (8/91 (9%) v. 7/4 058 (0.2%); p<0.001). Neonatal outcomes were favourable. No significant differences in COVID-19 risk factors, disease severity, and maternal/neonatal outcome were noted for PLHIV v. those without HIV. CONCLUSIONS: In this cohort of high-risk pregnant women, the impact of COVID-19 was severe, significantly increasing maternal mortality risk compared with baseline rates. Virally suppressed HIV infection was not associated with worse COVID-19 outcomes in pregnancy.


Subject(s)
COVID-19/complications , HIV Infections/epidemiology , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome , Adult , CD4 Lymphocyte Count , Cohort Studies , Female , Humans , Infant, Newborn , Maternal Mortality , Pregnancy , Pregnancy Complications, Infectious/virology , Pregnancy, High-Risk , Prospective Studies , South Africa
16.
Front Immunol ; 12: 748881, 2021.
Article in English | MEDLINE | ID: covidwho-1551504

ABSTRACT

Olfactory and taste disorders (OTD) are commonly found as presenting symptoms of SARS-CoV-2 infection in patients with clinically mild COVID-19. Virus-specific T cells are thought to play an important role in the clearance of SARS-CoV-2; therefore the study of T cell specific immune responses in patients with mild symptoms may help to understand their possible role in protection from severe disease. We evaluated SARS-CoV-2-specific T cell responses to four different peptide megapools covering all SARS-CoV-2 proteins during the acute phase of the disease in 33 individuals with mild or no other symptom beside OTD and in 22 age-matched patients with severe infection. A control group of 15 outpatients with OTD and consistently negative nasopharyngeal SARS-CoV-2 RNA swabs and virus-specific IgG serology was included in the study. Increased frequencies of virus-specific CD4+ and CD8+ T cells were found in SARS-CoV-2 positive patients with OTD compared with those with severe COVID-19 and with SARS-CoV-2 negative OTD individuals. Moreover, enhanced CD4+ and CD8+ T-cell activation induced by SARS-CoV-2 peptides was associated with higher interferon (IFN)γ production. Increased frequencies of Spike (S1/S2)-specific CD4+ T cells showing enhanced IFNγ secretion and granzyme B content were associated with serum spike-specific IgG in the OTD group. In conclusion, patients with SARS-CoV-2 induced OTD develop highly functional virus-specific CD4+ and CD8+ T cells during the symptomatic phase of the disease, suggesting that robust and coordinated T-cell responses provide protection against extension of COVID-19 to the lower respiratory tract.


Subject(s)
Ageusia/pathology , Anosmia/pathology , Antibodies, Viral/blood , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , SARS-CoV-2/immunology , Antibodies, Viral/immunology , CD4 Lymphocyte Count , COVID-19/immunology , COVID-19/pathology , Cytokines/blood , Humans , Interferon-gamma/blood , Interferon-gamma/immunology , Spike Glycoprotein, Coronavirus/immunology
17.
PLoS One ; 16(12): e0260251, 2021.
Article in English | MEDLINE | ID: covidwho-1546950

ABSTRACT

There continue to be conflicting data regarding the outcomes of people with HIV (PWH) who have COVID-19 infection with most studies describing the early epidemic. We present a single site experience spanning a later timeframe from the first report on January 21, 2020 to January 20, 2021 and describe clinical outcomes and predictors of hospitalization among a cohort of PWH in an urban center in Connecticut, USA. Among 103 PWH with controlled HIV disease, hospitalization occurred in 33% and overall mortality was 1%. HIV associated factors (CD4 count, HIV viral suppression) were not associated with hospitalization. Chronic lung disease (OR: 3.35, 95% CI:1.28-8.72), and cardiovascular disease (OR: 3.4, 95% CI:1.27-9.12) were independently associated with hospitalization. An increasing number of non-communicable comorbidities increased the likelihood of hospitalization (OR: 1.61, 95% CI:1.22-2.13).


Subject(s)
COVID-19/diagnosis , HIV Infections/pathology , Hospitalization/statistics & numerical data , Adult , Age Factors , Aged , CD4 Lymphocyte Count , COVID-19/complications , COVID-19/virology , Cardiovascular Diseases/complications , Comorbidity , Connecticut , Female , HIV Infections/complications , HIV Infections/mortality , Humans , Male , Middle Aged , Noncommunicable Diseases/epidemiology , Odds Ratio , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification
19.
Eur J Immunol ; 52(2): 352-355, 2022 02.
Article in English | MEDLINE | ID: covidwho-1530141

ABSTRACT

A late presenter AIDS patient with severe T cell depletion presented non-severe COVID-19 symptoms, with prolonged viral shedding. Our case report supports the hypothesis that an effective T cell response may be dispensable for the control of COVID-19 progression to severe forms, while it may be necessary for SARS-CoV-2 clearance.


Subject(s)
Acquired Immunodeficiency Syndrome/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Acquired Immunodeficiency Syndrome/blood , Adult , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , COVID-19/blood , Female , Humans , SARS-CoV-2/metabolism
20.
Medicine (Baltimore) ; 100(41): e27418, 2021 Oct 15.
Article in English | MEDLINE | ID: covidwho-1501202

ABSTRACT

ABSTRACT: The occurrence of COVID-19 pandemic had a significant negative effect on health care systems over the last year. Health care providers were forced to focus mainly on COVID-19 patients, neglecting in many cases equally important diseases, both acute and chronic. Therefore, also screening and diagnostic strategies for HIV could have been significantly impaired.This retrospective, multicenter, observational study aimed at assessing the number and characteristics of new HIV/AIDS diagnoses during COVID-19 pandemic in Italy and compared characteristics of people living with HIV at diagnosis between pre- and post-COVID-19 era (2019 vs 2020).Our results showed a significant reduction of HIV diagnoses during pandemic. By contrast, people living with HIV during pandemic were older and were diagnosed in earlier stage of disease (considering CD4+ T cell count) compared to those who were diagnosed the year before. Moreover, there was a significant decrease of new HIV diagnoses among men who have sex with men, probably for the impact of social distancing and restriction applied by the Italian Government. Late presentation incidence, if numbers in 2020 were lower than those in 2019, is still an issue.Routinely performing HIV testing in patients with suspected SARS-CoV-2 infection is identifying and linking to care underdiagnosed people living with HIV earlier. Thus, combined tests (HIV and SARS-CoV-2) should be implemented in patients with SARS-CoV-2 symptoms overlapping HIV's ones. Lastly, our results lastly showed how urgent implementation of a national policy for HIV screening is necessary.


Subject(s)
Delivery of Health Care/organization & administration , HIV Infections/epidemiology , Mass Screening/statistics & numerical data , Adult , CD4 Lymphocyte Count/statistics & numerical data , COVID-19/epidemiology , Cross-Sectional Studies , Female , HIV Infections/diagnosis , Humans , Italy/epidemiology , Male , Mass Screening/organization & administration , Middle Aged , Pandemics , Retrospective Studies , Risk Factors , SARS-CoV-2
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