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2.
Clin Infect Dis ; 73(10): 1901-1905, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1522150

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic and associated public health responses have disrupted daily living activities with economic and health consequences globally. We observed transient decreases in human immunodeficiency virus (HIV) clinic visit adherence and food security among persons living with HIV early in the pandemic, and an increase in viral suppression later in the pandemic.


Subject(s)
COVID-19 , HIV Infections , Food Security , HIV , HIV Infections/epidemiology , Humans , Pandemics , SARS-CoV-2
7.
Clin Infect Dis ; 73(7): e2095-e2106, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1455268

ABSTRACT

BACKGROUND: Evidence is conflicting about how human immunodeficiency virus (HIV) modulates coronavirus disease 2019 (COVID-19). We compared the presentation characteristics and outcomes of adults with and without HIV who were hospitalized with COVID-19 at 207 centers across the United Kingdom and whose data were prospectively captured by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) World Health Organization (WHO) Clinical Characterization Protocol (CCP) study. METHODS: We used Kaplan-Meier methods and Cox regression to describe the association between HIV status and day-28 mortality, after separate adjustment for sex, ethnicity, age, hospital acquisition of COVID-19 (definite hospital acquisition excluded), presentation date, 10 individual comorbidities, and disease severity at presentation (as defined by hypoxia or oxygen therapy). RESULTS: Among 47 592 patients, 122 (0.26%) had confirmed HIV infection, and 112/122 (91.8%) had a record of antiretroviral therapy. At presentation, HIV-positive people were younger (median 56 vs 74 years; P < .001) and had fewer comorbidities, more systemic symptoms and higher lymphocyte counts and C-reactive protein levels. The cumulative day-28 mortality was similar in the HIV-positive versus HIV-negative groups (26.7% vs. 32.1%; P = .16), but in those under 60 years of age HIV-positive status was associated with increased mortality (21.3% vs. 9.6%; P < .001 [log-rank test]). Mortality was higher among people with HIV after adjusting for age (adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.01-2.14; P = .05), and the association persisted after adjusting for the other variables (aHR 1.69; 95% CI 1.15-2.48; P = .008) and when restricting the analysis to people aged <60 years (aHR 2.87; 95% CI 1.70-4.84; P < .001). CONCLUSIONS: HIV-positive status was associated with an increased risk of day-28 mortality among patients hospitalized for COVID-19.


Subject(s)
COVID-19 , HIV Infections , Adult , HIV , HIV Infections/complications , HIV Infections/epidemiology , Hospitalization , Humans , Middle Aged , Observational Studies as Topic , SARS-CoV-2 , United Kingdom , World Health Organization
8.
Clin Infect Dis ; 73(7): e1964-e1972, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1455261

ABSTRACT

BACKGROUND: People living with human immunodeficiency virus (HIV) may have numerous risk factors for acquiring coronavirus disease 2019 (COVID-19) and developing severe outcomes, but current data are conflicting. METHODS: Health-care providers enrolled consecutively, by nonrandom sampling, people living with HIV (PWH) with lab-confirmed COVID-19, diagnosed at their facilities between 1 April and 1 July 2020. Deidentified data were entered into an electronic Research Electronic Data Capture (REDCap) system. The primary endpoint was a severe outcome, defined as a composite endpoint of intensive care unit (ICU) admission, mechanical ventilation, or death. The secondary outcome was the need for hospitalization. RESULTS: There were 286 patients included; the mean age was 51.4 years (standard deviation, 14.4), 25.9% were female, and 75.4% were African American or Hispanic. Most patients (94.3%) were on antiretroviral therapy, 88.7% had HIV virologic suppression, and 80.8% had comorbidities. Within 30 days of testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 164 (57.3%) patients were hospitalized, and 47 (16.5%) required ICU admission. Mortality rates were 9.4% (27/286) overall, 16.5% (27/164) among those hospitalized, and 51.5% (24/47) among those admitted to an ICU. The primary composite endpoint occurred in 17.5% (50/286) of all patients and 30.5% (50/164) of hospitalized patients. Older age, chronic lung disease, and hypertension were associated with severe outcomes. A lower CD4 count (<200 cells/mm3) was associated with the primary and secondary endpoints. There were no associations between the ART regimen or lack of viral suppression and the predefined outcomes. CONCLUSIONS: Severe clinical outcomes occurred commonly in PWH with COVID-19. The risks for poor outcomes were higher in those with comorbidities and lower CD4 cell counts, despite HIV viral suppression. CLINICAL TRIALS REGISTRATION: NCT04333953.


Subject(s)
COVID-19 , HIV Infections , Aged , Female , HIV , HIV Infections/drug therapy , HIV Infections/epidemiology , Hospitalization , Humans , Middle Aged , Registries , SARS-CoV-2
9.
Clin Infect Dis ; 73(7): e2086-e2094, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1455253

ABSTRACT

BACKGROUND: We aimed to describe the epidemiological, virological, and serological features of coronavirus disease 2019 (COVID-19) cases in people living with human immunodeficiency virus (HIV; PLWH). METHODS: This population-based cohort study identified all COVID-19 cases among all PLWH in Wuhan, China, by 16 April 2020. The epidemiological, virological, and serological features were analyzed based on the demographic data, temporal profile of nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the disease, and SARS-CoV-2-specific immunoglobin (Ig) M and G after recovery. RESULTS: From 1 January to 16 April 2020, 35 of 6001 PLWH experienced COVID-19, with a cumulative incidence of COVID-19 of 0.58% (95% confidence interval [CI], .42-.81%). Among the COVID-19 cases, 15 (42.86) had severe illness, with 2 deaths. The incidence, case-severity, and case-fatality rates of COVID-19 in PLWH were comparable to those in the entire population in Wuhan. There were 197 PLWH who had discontinued combination antiretroviral therapy (cART), 4 of whom experienced COVID-19. Risk factors for COVID-19 were age ≥50 years old and cART discontinuation. The median duration of SARS-CoV-2 viral shedding among confirmed COVID-19 cases in PLWH was 30 days (interquartile range, 20-46). Cases with high HIV viral loads (≥20 copies/mL) had lower IgM and IgG levels than those with low HIV viral loads (<20 copies/ml; median signal value divided by the cutoff value [S/CO] for IgM, 0.03 vs 0.11, respectively [P < .001]; median S/CO for IgG, 10.16 vs 17.04, respectively [P = .069]). CONCLUSIONS: Efforts are needed to maintain the persistent supply of antiretroviral treatment to elderly PLWH aged 50 years or above during the COVID-19 epidemic. The coinfection of HIV and SARS-CoV-2 might change the progression and prognosis of COVID-19 patients in PLWH.


Subject(s)
COVID-19 , HIV Infections , Aged , Cohort Studies , HIV , HIV Infections/complications , HIV Infections/epidemiology , Humans , Middle Aged , SARS-CoV-2
10.
Ghana Med J ; 54(4 Suppl): 121-124, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1436206

ABSTRACT

Coronavirus disease 2019 (COVID-19) is especially severe in patients with underlying chronic conditions, with increased risk of mortality. There is concern that people living with HIV (PLWH), especially those with severe immunosuppression, and COVID-19 may have severe disease and a negative clinical outcome. Most studies on COVID-19 in PLWH are from Asia, Europe and America where population dynamics, antiretroviral treatment coverage and coexisting opportunistic infections may differ from that in sub-Saharan Africa. We report on the clinical profile and outcome of three cases of PLWH co-infected with SARS-CoV-2. They all presented with fever, cough and breathlessness and also had advanced HIV infection as evidenced by opportunistic infections, high HIV viral loads and low CD4 counts. The patients responded favourably to the standard of care and were discharged home. Our findings suggest that PLWH with advanced immunosuppression may not necessarily have an unfavourable disease course and outcome. However, case-controlled studies with a larger population size are needed to better understand the impact of COVID-19 in this patient population. Funding: Not declared.


Subject(s)
COVID-19/virology , Coinfection/virology , HIV Infections/virology , HIV , Opportunistic Infections/virology , SARS-CoV-2 , Adult , Africa South of the Sahara , COVID-19/complications , Coinfection/complications , Female , HIV Infections/complications , Humans , Male , Middle Aged , Opportunistic Infections/complications , Viral Load
11.
Nat Commun ; 12(1): 5376, 2021 09 10.
Article in English | MEDLINE | ID: covidwho-1402068

ABSTRACT

Natural killer (NK) cells are important early responders against viral infections. Changes in metabolism are crucial to fuel NK cell responses, and altered metabolism is linked to NK cell dysfunction in obesity and cancer. However, very little is known about the metabolic requirements of NK cells during acute retroviral infection and their importance for antiviral immunity. Here, using the Friend retrovirus mouse model, we show that following infection NK cells increase nutrient uptake, including amino acids and iron, and reprogram their metabolic machinery by increasing glycolysis and mitochondrial metabolism. Specific deletion of the amino acid transporter Slc7a5 has only discrete effects on NK cells, but iron deficiency profoundly impaires NK cell antiviral functions, leading to increased viral loads. Our study thus shows the requirement of nutrients and metabolism for the antiviral activity of NK cells, and has important implications for viral infections associated with altered iron levels such as HIV and SARS-CoV-2.


Subject(s)
Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Retroviridae Infections/immunology , Animals , Bone Marrow , COVID-19 , Cytokines , HIV , HIV Infections , Large Neutral Amino Acid-Transporter 1/genetics , Large Neutral Amino Acid-Transporter 1/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitochondria , Retroviridae , Retroviridae Infections/virology , SARS-CoV-2 , Viral Load
12.
Am J Case Rep ; 22: e932467, 2021 Aug 11.
Article in English | MEDLINE | ID: covidwho-1404093

ABSTRACT

BACKGROUND Neurosyphilis is a bacterial infection of the brain and the spinal cord, caused by Treponema pallidum. Its nonspecific clinical presentation includes cognitive impairment and motor and/or sensory function compromise. Neurosyphilis infections in patients with HIV have increased over the past few years and many cases of neurosyphilis manifest in patients with HIV who have low CD4 T-cell counts and high viral loads (VL). However, there is extremely limited acknowledgement in the literature about neurosyphilis presentations in patients with HIV who have normal CD4 counts. CASE REPORT We present a neurosyphilis and HIV coinfection in a patient with a normal CD4 count and an undetectable VL. A 69-year-old woman with a medical history of HIV was on a prescribed antiretroviral treatment regimen. She presented in the Emergency Room in an unresponsive state, although this had been preceded by a period of rapidly progressive cognitive decline. Her brain computed tomography scan without contrast was unremarkable. Laboratory test results were within normal limits, except for a positive result for the microhemagglutination assay for Treponema pallidum antibodies and rapid plasma regain (RPR) test, which was highly suggestive of neurosyphilis as a presumed diagnosis. She showed remarkable clinical improvement after the initiation of conventional treatment for neurosyphilis, which is a 14-day regimen of intravenous penicillin G. CONCLUSIONS Given the broad neurological manifestations of neurosyphilis and its increasing incidence in patients with HIV, it is important to consider neurosyphilis in the differential diagnosis after ruling out other causes of encephalopathy, especially in patients with an undetectable VL and a normal CD4 count.


Subject(s)
HIV Infections , Neurosyphilis , Aged , CD4 Lymphocyte Count , Female , HIV , HIV Infections/complications , Humans , Neurosyphilis/complications , Neurosyphilis/diagnosis , Neurosyphilis/drug therapy , Penicillins , Viral Load
13.
Clin Infect Dis ; 73(5): e1222-e1227, 2021 09 07.
Article in English | MEDLINE | ID: covidwho-1398081

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented global challenge that substantially risks reversing the progress in ending human immunodeficiency virus (HIV). At the same time, it may offer the opportunity for a new era of HIV management. This viewpoint presents the impact of COVID-19 on HIV care, including the Joint United Nations Programme on HIV/AIDS (UNAIDS) "three 90s" targets. It outlines how to enhance a patient-centered care approach, now known as the "fourth 90," by integrating face-to-face patient-physician and telemedicine encounters. It suggests a framework for prevention and treatment of multimorbidity and frailty, to achieve a good health-related quality of life, and to preserve intrinsic capacity in all people living with HIV.


Subject(s)
COVID-19 , HIV Infections , HIV , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Quality of Life , SARS-CoV-2
15.
ACS Appl Mater Interfaces ; 12(50): 55614-55623, 2020 Dec 16.
Article in English | MEDLINE | ID: covidwho-1387129

ABSTRACT

Multiplexed detection of viral nucleic acids is important for rapid screening of viral infection. In this study, we present a molybdenum disulfide (MoS2) nanosheet-modified dendrimer droplet microarray (DMA) for rapid and sensitive detection of retroviral nucleic acids of human immunodeficiency virus-1 (HIV-1) and human immunodeficiency virus-2 (HIV-2) simultaneously. The DMA platform was fabricated by omniphobic-omniphilic patterning on a surface-grafted dendrimer substrate. Functionalized MoS2 nanosheets modified with fluorescent dye-labeled oligomer probes were prepatterned on positively charged amino-modified omniphilic spots to form a fluorescence resonance energy transfer (FRET) sensing microarray. With the formation of separated microdroplets of sample on the hydrophobic-hydrophilic micropattern, prepatterned oligomer probes specifically hybridized with the target HIV genes and detached from the MoS2 nanosheet surface due to weakening of the adsorption force, leading to fluorescence signal recovery. As a proof of concept, we used this microarray with a small sample size (<150 nL) for simultaneous detection of HIV-1 and HIV-2 nucleic acids with a limit of detection (LOD) of 50 pM. The multiplex detection capability was further demonstrated for simultaneous detection of five viral genes (HIV-1, HIV-2, ORFlab, and N genes of SARS-COV-2 and M gene of Influenza A). This work demonstrated the potential of this novel MoS2-DMA FRET sensing platform for high-throughput multiplexed viral nucleic acid screening.


Subject(s)
Biosensing Techniques , COVID-19/diagnosis , HIV Infections/diagnosis , HIV/isolation & purification , COVID-19/genetics , COVID-19/virology , Disulfides/chemistry , Fluorescence , Fluorescence Resonance Energy Transfer , HIV/pathogenicity , HIV Infections/genetics , HIV Infections/virology , Humans , Molybdenum/chemistry , Nanostructures/chemistry , Nucleic Acids/genetics , Nucleic Acids/isolation & purification , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity
16.
Viruses ; 12(7)2020 07 14.
Article in English | MEDLINE | ID: covidwho-1389516

ABSTRACT

Next-generation sequencing (NGS) offers a powerful opportunity to identify low-abundance, intra-host viral sequence variants, yet the focus of many bioinformatic tools on consensus sequence construction has precluded a thorough analysis of intra-host diversity. To take full advantage of the resolution of NGS data, we developed HAplotype PHylodynamics PIPEline (HAPHPIPE), an open-source tool for the de novo and reference-based assembly of viral NGS data, with both consensus sequence assembly and a focus on the quantification of intra-host variation through haplotype reconstruction. We validate and compare the consensus sequence assembly methods of HAPHPIPE to those of two alternative software packages, HyDRA and Geneious, using simulated HIV and empirical HIV, HCV, and SARS-CoV-2 datasets. Our validation methods included read mapping, genetic distance, and genetic diversity metrics. In simulated NGS data, HAPHPIPE generated pol consensus sequences significantly closer to the true consensus sequence than those produced by HyDRA and Geneious and performed comparably to Geneious for HIV gp120 sequences. Furthermore, using empirical data from multiple viruses, we demonstrate that HAPHPIPE can analyze larger sequence datasets due to its greater computational speed. Therefore, we contend that HAPHPIPE provides a more user-friendly platform for users with and without bioinformatics experience to implement current best practices for viral NGS assembly than other currently available options.


Subject(s)
Computational Biology/methods , High-Throughput Nucleotide Sequencing/methods , Viruses/genetics , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/virology , Genome, Viral , Genomics/methods , HIV/genetics , Haplotypes , Hepacivirus/genetics , Humans , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2
17.
Cells ; 10(9)2021 08 24.
Article in English | MEDLINE | ID: covidwho-1376745

ABSTRACT

As viruses are obligatory intracellular parasites, any step during their life cycle strictly depends on successful interaction with their particular host cells. In particular, their interaction with cellular membranes is of crucial importance for most steps in the viral replication cycle. Such interactions are initiated by uptake of viral particles and subsequent trafficking to intracellular compartments to access their replication compartments which provide a spatially confined environment concentrating viral and cellular components, and subsequently, employ cellular membranes for assembly and exit of viral progeny. The ability of viruses to actively modulate lipid composition such as sphingolipids (SLs) is essential for successful completion of the viral life cycle. In addition to their structural and biophysical properties of cellular membranes, some sphingolipid (SL) species are bioactive and as such, take part in cellular signaling processes involved in regulating viral replication. It is especially due to the progress made in tools to study accumulation and dynamics of SLs, which visualize their compartmentalization and identify interaction partners at a cellular level, as well as the availability of genetic knockout systems, that the role of particular SL species in the viral replication process can be analyzed and, most importantly, be explored as targets for therapeutic intervention.


Subject(s)
Sphingolipids/metabolism , Virus Diseases , Biological Transport , Cell Membrane/chemistry , Ceramides/metabolism , Drug Delivery Systems , HIV/growth & development , Host Microbial Interactions , Intracellular Membranes/chemistry , SARS-CoV-2/growth & development , Virion , Virus Replication , Viruses/growth & development
18.
J Gen Virol ; 102(8)2021 08.
Article in English | MEDLINE | ID: covidwho-1369239

ABSTRACT

Viruses may exploit the cardiovascular system to facilitate transmission or within-host dissemination, and the symptoms of many viral diseases stem at least in part from a loss of vascular integrity. The microvascular architecture is comprised of an endothelial cell barrier ensheathed by perivascular cells (pericytes). Pericytes are antigen-presenting cells (APCs) and play crucial roles in angiogenesis and the maintenance of microvascular integrity through complex reciprocal contact-mediated and paracrine crosstalk with endothelial cells. We here review the emerging ways that viruses interact with pericytes and pay consideration to how these interactions influence microvascular function and viral pathogenesis. Major outcomes of virus-pericyte interactions include vascular leakage or haemorrhage, organ tropism facilitated by barrier disruption, including viral penetration of the blood-brain barrier and placenta, as well as inflammatory, neurological, cognitive and developmental sequelae. The underlying pathogenic mechanisms may include direct infection of pericytes, pericyte modulation by secreted viral gene products and/or the dysregulation of paracrine signalling from or to pericytes. Viruses we cover include the herpesvirus human cytomegalovirus (HCMV, Human betaherpesvirus 5), the retrovirus human immunodeficiency virus (HIV; causative agent of acquired immunodeficiency syndrome, AIDS, and HIV-associated neurocognitive disorder, HAND), the flaviviruses dengue virus (DENV), Japanese encephalitis virus (JEV) and Zika virus (ZIKV), and the coronavirus severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2; causative agent of coronavirus disease 2019, COVID-19). We touch on promising pericyte-focussed therapies for treating the diseases caused by these important human pathogens, many of which are emerging viruses or are causing new or long-standing global pandemics.


Subject(s)
Cell Physiological Phenomena , Disease Susceptibility , Host-Pathogen Interactions , Pericytes/virology , Virus Diseases/metabolism , Virus Diseases/virology , Animals , Cell Communication , Dengue Virus/physiology , Disease Management , Endothelial Cells/virology , Endothelium/metabolism , Endothelium/virology , HIV/physiology , Humans , Paracrine Communication , SARS-CoV-2/physiology , Virus Diseases/diagnosis , Virus Diseases/therapy , Virus Physiological Phenomena
20.
Sex Transm Dis ; 48(8): 595-600, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1307602

ABSTRACT

BACKGROUND: People experiencing homelessness are disproportionately infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). In response to COVID-19, cities nationwide temporarily housed people experiencing homelessness in unused hotels. One such initiative in New Orleans also enacted a screening, counseling, and linkage-to-care model for HIV and HCV treatment for this temporarily housed population between May and July 2020. METHODS: A nonconcurrent cohort study was performed assessing follow up in the treatment of HIV and HCV for this population. Outcome data were collected on seropositive patients' electronic medical record to assess patient progression through the treatment cascade. RESULTS: Of 102 unhoused residents, 25 (24.5%) tested HCV seropositive. Of the HCV positive 21/25 (84%) were connected to the associated clinic for follow up care and 10 (40%) obtained HCV treatment medication. Furthermore, all 3 patients who tested seropositive for HIV either started or re-initiated antiviral treatment. The greatest barrier to providing medication for the HCV seropositive patients, once care was initiated, was loss-to-follow-up. CONCLUSIONS: Targeting homeless persons living in temporary residences for HCV and HIV screening can be effective at promoting access to care for those infected due to this population's high HCV seropositivity especially significant if the patient has a history of intravenous drug use or is older than 40 years. However, continued outreach strategies are needed to assist patients in retention of care.


Subject(s)
COVID-19 , HIV Infections , Hepatitis C , Homeless Persons , Cohort Studies , HIV , HIV Infections/drug therapy , HIV Infections/epidemiology , Hepacivirus , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Humans , New Orleans , Pandemics , SARS-CoV-2
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