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1.
PLoS One ; 16(12): e0260820, 2021.
Article in English | MEDLINE | ID: covidwho-1581771

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has caused widespread disruptions including to health services. In the early response to the pandemic many countries restricted population movements and some health services were suspended or limited. In late 2020 and early 2021 some countries re-imposed restrictions. Health authorities need to balance the potential harms of additional SARS-CoV-2 transmission due to contacts associated with health services against the benefits of those services, including fewer new HIV infections and deaths. This paper examines these trade-offs for select HIV services. METHODS: We used four HIV simulation models (Goals, HIV Synthesis, Optima HIV and EMOD) to estimate the benefits of continuing HIV services in terms of fewer new HIV infections and deaths. We used three COVID-19 transmission models (Covasim, Cooper/Smith and a simple contact model) to estimate the additional deaths due to SARS-CoV-2 transmission among health workers and clients. We examined four HIV services: voluntary medical male circumcision, HIV diagnostic testing, viral load testing and programs to prevent mother-to-child transmission. We compared COVID-19 deaths in 2020 and 2021 with HIV deaths occurring now and over the next 50 years discounted to present value. The models were applied to countries with a range of HIV and COVID-19 epidemics. RESULTS: Maintaining these HIV services could lead to additional COVID-19 deaths of 0.002 to 0.15 per 10,000 clients. HIV-related deaths averted are estimated to be much larger, 19-146 discounted deaths per 10,000 clients. DISCUSSION: While there is some additional short-term risk of SARS-CoV-2 transmission associated with providing HIV services, the risk of additional COVID-19 deaths is at least 100 times less than the HIV deaths averted by those services. Ministries of Health need to take into account many factors in deciding when and how to offer essential health services during the COVID-19 pandemic. This work shows that the benefits of continuing key HIV services are far larger than the risks of additional SARS-CoV-2 transmission.


Subject(s)
COVID-19/transmission , Health Services Accessibility/trends , Health Services/trends , COVID-19/complications , COVID-19/epidemiology , HIV Infections/complications , HIV Infections/epidemiology , HIV Infections/therapy , HIV-1/pathogenicity , Health Services Administration , Humans , Models, Theoretical , Pandemics/prevention & control , Risk Assessment/methods , SARS-CoV-2/pathogenicity
2.
Int J Mol Sci ; 22(21)2021 Oct 27.
Article in English | MEDLINE | ID: covidwho-1487420

ABSTRACT

Tetraspanins are transmembrane glycoproteins that have been shown increasing interest as host factors in infectious diseases. In particular, they were implicated in the pathogenesis of both non-enveloped (human papillomavirus (HPV)) and enveloped (human immunodeficiency virus (HIV), Zika, influenza A virus, (IAV), and coronavirus) viruses through multiple stages of infection, from the initial cell membrane attachment to the syncytium formation and viral particle release. However, the mechanisms by which different tetraspanins mediate their effects vary. This review aimed to compare and contrast the role of tetraspanins in the life cycles of HPV, HIV, Zika, IAV, and coronavirus viruses, which cause the most significant health and economic burdens to society. In doing so, a better understanding of the relative contribution of tetraspanins in virus infection will allow for a more targeted approach in the treatment of these diseases.


Subject(s)
Host-Pathogen Interactions/physiology , Tetraspanins/physiology , Virus Diseases/metabolism , Gene Expression Regulation, Viral , HIV-1/pathogenicity , Humans , Influenza A virus/pathogenicity , Papillomaviridae/pathogenicity , SARS-CoV-2/pathogenicity , Virus Diseases/genetics , Virus Diseases/virology , Virus Internalization , Zika Virus/pathogenicity
3.
Viruses ; 13(10)2021 09 26.
Article in English | MEDLINE | ID: covidwho-1485180

ABSTRACT

Nascent HIV-1 particles incorporate the viral envelope glycoprotein and multiple host transmembrane proteins during assembly at the plasma membrane. At least some of these host transmembrane proteins on the surface of virions are reported as pro-viral factors that enhance virus attachment to target cells or facilitate trans-infection of CD4+ T cells via interactions with non-T cells. In addition to the pro-viral factors, anti-viral transmembrane proteins are incorporated into progeny virions. These virion-incorporated transmembrane proteins inhibit HIV-1 entry at the point of attachment and fusion. In infected polarized CD4+ T cells, HIV-1 Gag localizes to a rear-end protrusion known as the uropod. Regardless of cell polarization, Gag colocalizes with and promotes the virion incorporation of a subset of uropod-directed host transmembrane proteins, including CD162, CD43, and CD44. Until recently, the functions of these virion-incorporated proteins had not been clear. Here, we review the recent findings about the roles played by virion-incorporated CD162, CD43, and CD44 in HIV-1 spread to CD4+ T cells.


Subject(s)
HIV Infections/metabolism , Hyaluronan Receptors/metabolism , Leukosialin/metabolism , Membrane Glycoproteins/metabolism , Cell Membrane/metabolism , HIV Infections/genetics , HIV-1/genetics , HIV-1/metabolism , HIV-1/pathogenicity , Host-Pathogen Interactions , Humans , Hyaluronan Receptors/genetics , Leukosialin/genetics , Membrane Glycoproteins/genetics , Membrane Proteins/metabolism , T-Lymphocytes/metabolism , T-Lymphocytes/virology , Virion/metabolism , Virus Assembly , Virus Attachment , gag Gene Products, Human Immunodeficiency Virus/metabolism
4.
Int J Med Sci ; 18(3): 846-851, 2021.
Article in English | MEDLINE | ID: covidwho-1389719

ABSTRACT

In the last 50 years we have experienced two big pandemics, the HIV pandemic and the pandemic caused by SARS-CoV-2. Both pandemics are caused by RNA viruses and have reached us from animals. These two viruses are different in the transmission mode and in the symptoms they generate. However, they have important similarities: the fear in the population, increase in proinflammatory cytokines that generate intestinal microbiota modifications or NETosis production by polymorphonuclear neutrophils, among others. They have been implicated in the clinical, prognostic and therapeutic attitudes.


Subject(s)
COVID-19/epidemiology , HIV Infections/epidemiology , HIV-1/pathogenicity , Pandemics/history , SARS-CoV-2/pathogenicity , COVID-19/immunology , COVID-19/psychology , COVID-19/transmission , Cytokines/blood , Cytokines/immunology , Extracellular Traps/immunology , Extracellular Traps/metabolism , Fear , Global Burden of Disease/statistics & numerical data , HIV Infections/immunology , HIV Infections/psychology , HIV Infections/transmission , HIV-1/immunology , HIV-1/isolation & purification , History, 20th Century , History, 21st Century , Host-Pathogen Interactions/immunology , Humans , Inflammation Mediators/blood , Inflammation Mediators/immunology , Mortality , Neutrophils/immunology , Neutrophils/metabolism , Pandemics/statistics & numerical data , Prognosis , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
5.
Molecules ; 25(12)2020 Jun 26.
Article in English | MEDLINE | ID: covidwho-1389454

ABSTRACT

Viruses can be spread from one person to another; therefore, they may cause disorders in many people, sometimes leading to epidemics and even pandemics. New, previously unstudied viruses and some specific mutant or recombinant variants of known viruses constantly appear. An example is a variant of coronaviruses (CoV) causing severe acute respiratory syndrome (SARS), named SARS-CoV-2. Some antiviral drugs, such as remdesivir as well as antiretroviral drugs including darunavir, lopinavir, and ritonavir are suggested to be effective in treating disorders caused by SARS-CoV-2. There are data on the utilization of antiretroviral drugs against SARS-CoV-2. Since there are many studies aimed at the identification of the molecular mechanisms of human immunodeficiency virus type 1 (HIV-1) infection and the development of novel therapeutic approaches against HIV-1, we used HIV-1 for our case study to identify possible molecular pathways shared by SARS-CoV-2 and HIV-1. We applied a text and data mining workflow and identified a list of 46 targets, which can be essential for the development of infections caused by SARS-CoV-2 and HIV-1. We show that SARS-CoV-2 and HIV-1 share some molecular pathways involved in inflammation, immune response, cell cycle regulation.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/metabolism , Data Mining/methods , HIV Infections/epidemiology , HIV Infections/metabolism , Host-Pathogen Interactions/immunology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/metabolism , Anti-Inflammatory Agents/therapeutic use , Antigens, Differentiation/genetics , Antigens, Differentiation/immunology , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Complement System Proteins/genetics , Complement System Proteins/immunology , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Databases, Genetic , Gene Expression Regulation , HIV Infections/drug therapy , HIV Infections/immunology , HIV-1/drug effects , HIV-1/immunology , HIV-1/pathogenicity , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/genetics , Humans , Immunity, Innate/drug effects , Immunologic Factors/therapeutic use , Inflammation , Interferons/genetics , Interferons/immunology , Interleukins/genetics , Interleukins/immunology , Metabolic Networks and Pathways/drug effects , Metabolic Networks and Pathways/genetics , Metabolic Networks and Pathways/immunology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Repressor Proteins/genetics , Repressor Proteins/immunology , SARS-CoV-2 , Signal Transduction , Toll-Like Receptors/genetics , Toll-Like Receptors/immunology , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/immunology
6.
Retrovirology ; 18(1): 21, 2021 08 03.
Article in English | MEDLINE | ID: covidwho-1365362

ABSTRACT

HIV-1 persists in infected individuals despite years of antiretroviral therapy (ART), due to the formation of a stable and long-lived latent viral reservoir. Early ART can reduce the latent reservoir and is associated with post-treatment control in people living with HIV (PLWH). However, even in post-treatment controllers, ART cessation after a period of time inevitably results in rebound of plasma viraemia, thus lifelong treatment for viral suppression is indicated. Due to the difficulties of sustained life-long treatment in the millions of PLWH worldwide, a cure is undeniably necessary. This requires an in-depth understanding of reservoir formation and dynamics. Differences exist in treatment guidelines and accessibility to treatment as well as social stigma between low- and-middle income countries (LMICs) and high-income countries. In addition, demographic differences exist in PLWH from different geographical regions such as infecting viral subtype and host genetics, which can contribute to differences in the viral reservoir between different populations. Here, we review topics relevant to HIV-1 cure research in LMICs, with a focus on sub-Saharan Africa, the region of the world bearing the greatest burden of HIV-1. We present a summary of ART in LMICs, highlighting challenges that may be experienced in implementing a HIV-1 cure therapeutic. Furthermore, we discuss current research on the HIV-1 latent reservoir in different populations, highlighting research in LMIC and gaps in the research that may facilitate a global cure. Finally, we discuss current experimental cure strategies in the context of their potential application in LMICs.


Subject(s)
Antiretroviral Therapy, Highly Active/standards , Developing Countries/statistics & numerical data , Disease Reservoirs/virology , HIV Infections/drug therapy , Virus Latency/drug effects , Africa South of the Sahara/epidemiology , Antiretroviral Therapy, Highly Active/methods , Antiretroviral Therapy, Highly Active/statistics & numerical data , Cost of Illness , HIV Infections/epidemiology , HIV Infections/prevention & control , HIV-1/genetics , HIV-1/pathogenicity , Humans
7.
Biochim Biophys Acta Mol Basis Dis ; 1867(12): 166244, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1356140

ABSTRACT

The placenta provides a significant physical and physiological barrier to prevent fetal infection during pregnancy. Nevertheless, it is at times breached by pathogens and leads to vertical transmission of infection from mother to fetus. This review will focus specifically on the Zika flavivirus, the HIV retrovirus and the emerging SARS-CoV2 coronavirus, which have affected pregnant women and their offspring in recent epidemics. In particular, we will address how viral infections affect the immune response at the maternal-fetal interface and how the placental barrier is physically breached and discuss the consequences of infection on various aspects of placental function to support fetal growth and development. Improved understanding of how the placenta responds to viral infections will lay the foundation for developing therapeutics to these and emergent viruses, to minimise the harms of infection to the offspring.


Subject(s)
Placenta/virology , Pregnancy Complications, Infectious/virology , Virus Diseases/physiopathology , COVID-19/metabolism , Female , Fetus/virology , HIV Infections/metabolism , HIV-1/pathogenicity , Humans , Infectious Disease Transmission, Vertical/statistics & numerical data , Placenta/metabolism , Pregnancy , Pregnancy Complications, Infectious/epidemiology , SARS-CoV-2/pathogenicity , Zika Virus/pathogenicity , Zika Virus Infection/metabolism
8.
Viruses ; 13(6)2021 06 18.
Article in English | MEDLINE | ID: covidwho-1282641

ABSTRACT

This article reviews the current knowledge on how viruses may utilize Extracellular Vesicle Assisted Inflammatory Load (EVAIL) to exert pathologic activities. Viruses are classically considered to exert their pathologic actions through acute or chronic infection followed by the host response. This host response causes the release of cytokines leading to vascular endothelial cell dysfunction and cardiovascular complications. However, viruses may employ an alternative pathway to soluble cytokine-induced pathologies-by initiating the release of extracellular vesicles (EVs), including exosomes. The best-understood example of this alternative pathway is human immunodeficiency virus (HIV)-elicited EVs and their propensity to harm vascular endothelial cells. Specifically, an HIV-encoded accessory protein called the "negative factor" (Nef) was demonstrated in EVs from the body fluids of HIV patients on successful combined antiretroviral therapy (ART); it was also demonstrated to be sufficient in inducing endothelial and cardiovascular dysfunction. This review will highlight HIV-Nef as an example of how HIV can produce EVs loaded with proinflammatory cargo to disseminate cardiovascular pathologies. It will further discuss whether EV production can explain SARS-CoV-2-mediated pulmonary and cardiovascular pathologies.


Subject(s)
Extracellular Vesicles/immunology , Extracellular Vesicles/virology , Inflammation/virology , COVID-19/complications , COVID-19/immunology , COVID-19/physiopathology , Cardiovascular Diseases/virology , Endothelial Cells/pathology , Endothelial Cells/virology , Exosomes/metabolism , HIV Infections/complications , HIV Infections/immunology , HIV Infections/physiopathology , HIV-1/pathogenicity , Humans , SARS-CoV-2/pathogenicity
9.
Viruses ; 13(6)2021 06 12.
Article in English | MEDLINE | ID: covidwho-1282640

ABSTRACT

There is a growing number of perinatally HIV-1-infected children worldwide who must maintain life-long ART. In early life, HIV-1 infection is established in an immunologically inexperienced environment in which maternal ART and immune dynamics during pregnancy play a role in reservoir establishment. Children that initiated early antiretroviral therapy (ART) and maintained long-term suppression of viremia have smaller and less diverse HIV reservoirs than adults, although their proviral landscape during ART is reported to be similar to that of adults. The ability of these early infected cells to persist long-term through clonal expansion poses a major barrier to finding a cure. Furthermore, the effects of life-long HIV persistence and ART are yet to be understood, but growing evidence suggests that these individuals are at an increased risk for developing non-AIDS-related comorbidities, which underscores the need for an HIV cure.


Subject(s)
Anti-Retroviral Agents/therapeutic use , Antiretroviral Therapy, Highly Active , Disease Reservoirs/virology , HIV Infections/virology , HIV-1/pathogenicity , Child , DNA, Viral/genetics , Female , HIV-1/genetics , Humans , Infectious Disease Transmission, Vertical , Pregnancy , Proviruses/genetics , Viral Load , Viremia/drug therapy
10.
11.
Int J Mol Sci ; 22(11)2021 May 26.
Article in English | MEDLINE | ID: covidwho-1256559

ABSTRACT

Ceramide is a lipid messenger at the heart of sphingolipid metabolism. In concert with its metabolizing enzymes, particularly sphingomyelinases, it has key roles in regulating the physical properties of biological membranes, including the formation of membrane microdomains. Thus, ceramide and its related molecules have been attributed significant roles in nearly all steps of the viral life cycle: they may serve directly as receptors or co-receptors for viral entry, form microdomains that cluster entry receptors and/or enable them to adopt the required conformation or regulate their cell surface expression. Sphingolipids can regulate all forms of viral uptake, often through sphingomyelinase activation, and mediate endosomal escape and intracellular trafficking. Ceramide can be key for the formation of viral replication sites. Sphingomyelinases often mediate the release of new virions from infected cells. Moreover, sphingolipids can contribute to viral-induced apoptosis and morbidity in viral diseases, as well as virus immune evasion. Alpha-galactosylceramide, in particular, also plays a significant role in immune modulation in response to viral infections. This review will discuss the roles of ceramide and its related molecules in the different steps of the viral life cycle. We will also discuss how novel strategies could exploit these for therapeutic benefit.


Subject(s)
Ceramides/metabolism , HIV-1/metabolism , Influenza A virus/metabolism , SARS-CoV-2/metabolism , Virus Diseases/metabolism , Virus Diseases/virology , Apoptosis/drug effects , Apoptosis/immunology , Ceramides/chemistry , Gene Expression Regulation, Viral , HIV-1/pathogenicity , Humans , Immunomodulation , Influenza A virus/pathogenicity , SARS-CoV-2/pathogenicity , Virion/growth & development , Virus Diseases/immunology , Virus Internalization , Virus Replication/drug effects , Virus Replication/immunology
12.
Lancet HIV ; 8(6): e334-e341, 2021 06.
Article in English | MEDLINE | ID: covidwho-1210023

ABSTRACT

BACKGROUND: Most cohorts show similar or lower COVID-19 incidence among people living with HIV compared with the general population. However, incidence might be affected by lower testing rates among vulnerable populations. We aimed to compare SARS-CoV-2 IgG seroprevalence, disease severity, and neutralising antibody activity after infection among people with and without HIV receiving care in a county hospital system over a 3-month period. METHODS: In this matched case-control observational study, remnant serum samples were collected between Aug 1 and Oct 31, 2020, from all people living with HIV who underwent routine outpatient laboratory testing in a municipal health-care system (San Francisco General Hospital, CA, USA). Samples from people living with HIV were date of collection-matched (same day) and age-matched (±5 years) to samples from randomly selected adults (aged 18 years or older) without HIV receiving care for chronic conditions at the same hospital. We compared seroprevalence by HIV status via mixed-effects logistic regression models, accounting for the matched structure of the data (random effects for the matched group), adjusting for age, sex, race or ethnicity, and clinical factors (ie, history of cardiovascular or pulmonary disease, and type 2 diabetes). Severe COVID-19 was assessed in participants with past SARS-CoV-2 (IgG or PCR) infection by chart review and compared with multivariable mixed-effects logistic regression, adjusting for age and sex. SARS-CoV-2 IgG, neutralising antibody titres, and antibody avidity were measured in serum of participants with previous positive PCR tests and compared with multivariable mixed-effects models, adjusting for age, sex, and time since PCR-confirmed SARS-CoV-2 infection. FINDINGS: 1138 samples from 955 people living with HIV and 1118 samples from 1062 people without HIV were tested. SARS-CoV-2 IgG seroprevalence was 3·7% (95% CI 2·4 to 5·0) among people with HIV compared with 7·4% (5·7 to 9·2) among people without HIV (adjusted odds ratio 0·50, 95% CI 0·30 to 0·83). Among 31 people with HIV and 70 people without HIV who had evidence of past infection, the odds of severe COVID-19 were 5·52 (95% CI 1·01 to 64·48) times higher among people living with HIV. Adjusting for time since PCR-confirmed infection, SARS-CoV-2 IgG concentrations were lower (percentage change -53%, 95% CI -4 to -76), pseudovirus neutralising antibody titres were lower (-67%, -25 to -86), and avidity was similar (7%, -73 to 87) among people living with HIV compared with those without HIV. INTERPRETATION: Although fewer infections were detected by SARS-CoV-2 IgG testing among people living with HIV than among those without HIV, people with HIV had more cases of severe COVID-19. Among people living with HIV with past SARS-CoV-2 infection, lower IgG concentrations and pseudovirus neutralising antibody titres might reflect a diminished serological response to infection, and the similar avidity could be driven by similar time since infection. FUNDING: US National Institute of Allergy and Infectious Diseases, US National Institutes of Health.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , HIV Infections/immunology , Immunoglobulin G/blood , SARS-CoV-2/immunology , Aged , COVID-19/blood , COVID-19/epidemiology , COVID-19/virology , Case-Control Studies , Female , HIV Infections/blood , HIV Infections/epidemiology , HIV Infections/virology , HIV-1/immunology , HIV-1/pathogenicity , Humans , Male , Middle Aged , Neutralization Tests , SARS-CoV-2/pathogenicity , San Francisco/epidemiology , Seroepidemiologic Studies , Severity of Illness Index
13.
AIDS Res Hum Retroviruses ; 37(4): 255-265, 2021 04.
Article in English | MEDLINE | ID: covidwho-1207216

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of COVID-19, a disease that as of July 10, 2020, has infected >12 million people and killed >500,000. COVID-19 infection leads to acute respiratory distress syndrome in a subset of patients and is a primary driver of acute morbidity in infected persons. However, it is becoming increasingly clear that SARS-CoV-2 infection drives dysfunction and pathology outside the lungs, including reports of renal, cardiac, and neurological complications. In this study, we summarize the known incidence and evidence of neurological complications associated with SARS-CoV-2 infection and other pathogenic coronaviruses. These studies describe a poorly understood spectrum of COVID-19 central nervous system symptoms, ranging from common and subclinical issues such as anosmia and headache to more concerning reports of stroke and encephalopathy. We discuss potential mechanisms of pathogenesis, including a discussion of how the understanding of neurological complications known to occur in HIV-1 patients may provide insight into SARS-CoV-2-associated neurological manifestations. Specifically, three hypotheses are discussed that are informed by decades of knowledge about HIV pathogenesis in the brain, which include a potential direct viral effect, an indirect viral effect, and/or a neuroimmune axis effect. Individually or in combination these potential effects may contribute to COVID-19 neurological complications.


Subject(s)
Brain/virology , COVID-19/virology , HIV Infections/virology , SARS-CoV-2/pathogenicity , HIV-1/pathogenicity , Humans
14.
Lancet HIV ; 8(1): e24-e32, 2021 01.
Article in English | MEDLINE | ID: covidwho-1059582

ABSTRACT

BACKGROUND: Whether HIV infection is associated with risk of death due to COVID-19 is unclear. We aimed to investigate this association in a large-scale population-based study in England. METHODS: We did a retrospective cohort study. Working on behalf of NHS England, we used the OpenSAFELY platform to analyse routinely collected electronic primary care data linked to national death registrations. We included all adults (aged ≥18 years) alive and in follow-up on Feb 1, 2020, and with at least 1 year of continuous registration with a general practitioner before this date. People with a primary care record for HIV infection were compared with people without HIV. The outcome was COVID-19 death, defined as the presence of International Classification of Diseases 10 codes U07.1 or U07.2 anywhere on the death certificate. Cox regression models were used to estimate the association between HIV infection and COVID-19 death; they were initially adjusted for age and sex, then we added adjustment for index of multiple deprivation and ethnicity, and then for a broad range of comorbidities. Interaction terms were added to assess effect modification by age, sex, ethnicity, comorbidities, and calendar time. RESULTS: 17 282 905 adults were included, of whom 27 480 (0·16%) had HIV recorded. People living with HIV were more likely to be male, of Black ethnicity, and from a more deprived geographical area than the general population. 14 882 COVID-19 deaths occurred during the study period, with 25 among people with HIV. People living with HIV had higher risk of COVID-19 death than those without HIV after adjusting for age and sex: hazard ratio (HR) 2·90 (95% CI 1·96-4·30; p<0·0001). The association was attenuated, but risk remained high, after adjustment for deprivation, ethnicity, smoking and obesity: adjusted HR 2·59 (95% CI 1·74-3·84; p<0·0001). There was some evidence that the association was larger among people of Black ethnicity: HR 4·31 (95% CI 2·42-7·65) versus 1·84 (1·03-3·26) in non-Black individuals (p-interaction=0·044). INTERPRETATION: People with HIV in the UK seem to be at increased risk of COVID-19 mortality. Targeted policies should be considered to address this raised risk as the pandemic response evolves. FUNDING: Wellcome, Royal Society, National Institute for Health Research, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, Health Data Research UK.


Subject(s)
COVID-19/epidemiology , COVID-19/mortality , HIV Infections/epidemiology , HIV Infections/mortality , Pandemics , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/ethnology , COVID-19/virology , Coinfection , Female , HIV Infections/ethnology , HIV Infections/virology , HIV-1/pathogenicity , Humans , Male , Middle Aged , Obesity/physiopathology , Proportional Hazards Models , Retrospective Studies , Risk Factors , SARS-CoV-2/pathogenicity , Sex Factors , Smoking/physiopathology , Social Class , United Kingdom/epidemiology
15.
PLoS Biol ; 18(12): e3000963, 2020 12.
Article in English | MEDLINE | ID: covidwho-1040033

ABSTRACT

Approximately 28% of the human population have been exposed to Mycobacterium tuberculosis (MTB), with the overwhelming majority of infected individuals not developing disease (latent TB infection (LTBI)). While it is known that uncontrolled HIV infection is a major risk factor for the development of TB, the effect of underlying LTBI on HIV disease progression is less well characterized, in part because longitudinal data are lacking. We sorted all participants of the Swiss HIV Cohort Study (SHCS) with at least 1 documented MTB test into one of the 3 groups: MTB uninfected, LTBI, or active TB. To detect differences in the HIV set point viral load (SPVL), linear regression was used; the frequency of the most common opportunistic infections (OIs) in the SHCS between MTB uninfected patients, patients with LTBI, and patients with active TB were compared using logistic regression and time-to-event analyses. In adjusted models, we corrected for baseline demographic characteristics, i.e., HIV transmission risk group and gender, geographic region, year of HIV diagnosis, and CD4 nadir. A total of 13,943 SHCS patients had at least 1 MTB test documented, of whom 840 (6.0%) had LTBI and 770 (5.5%) developed active TB. Compared to MTB uninfected patients, LTBI was associated with a 0.24 decreased log HIV SPVL in the adjusted model (p < 0.0001). Patients with LTBI had lower odds of having candida stomatitis (adjusted odds ratio (OR) = 0.68, p = 0.0035) and oral hairy leukoplakia (adjusted OR = 0.67, p = 0.033) when compared to MTB uninfected patients. The association of LTBI with a reduced HIV set point virus load and fewer unrelated infections in HIV/TB coinfected patients suggests a more complex interaction between LTBI and HIV than previously assumed.


Subject(s)
HIV Infections/complications , Latent Tuberculosis/complications , Latent Tuberculosis/diagnosis , AIDS-Related Opportunistic Infections/complications , AIDS-Related Opportunistic Infections/etiology , AIDS-Related Opportunistic Infections/microbiology , Adult , CD4-Positive T-Lymphocytes , Cohort Studies , Disease Progression , Female , HIV Infections/metabolism , HIV-1/pathogenicity , Humans , Interferon-gamma , Latent Tuberculosis/metabolism , Male , Middle Aged , Mycobacterium tuberculosis/pathogenicity , Opportunistic Infections/complications , Risk , Tuberculosis/complications , Tuberculosis/diagnosis , Viral Load/immunology
16.
J Neurovirol ; 27(1): 168-170, 2021 02.
Article in English | MEDLINE | ID: covidwho-1009224

ABSTRACT

People living with HIV (PLWH) may be at higher risk for adverse outcomes indirectly associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2). When comparing responses to questionnaires administered when social distancing and quarantine guidelines were first implemented, we found that PLWH were more likely to have restricted access to medical care, increased financial stress, increased symptoms of anxiety and depression, and increased substance use compared to demographically-similar people without HIV.


Subject(s)
Anxiety/epidemiology , COVID-19/epidemiology , Depression/epidemiology , HIV Infections/epidemiology , Pandemics , Stress, Psychological/epidemiology , Substance-Related Disorders/epidemiology , Adult , Aged , Anxiety/economics , Anxiety/psychology , Anxiety/virology , COVID-19/economics , COVID-19/psychology , COVID-19/virology , Comorbidity , Depression/economics , Depression/psychology , Depression/virology , Female , HIV Infections/economics , HIV Infections/psychology , HIV Infections/virology , HIV-1/pathogenicity , Health Services Accessibility/economics , Health Services Accessibility/ethics , Humans , Male , Middle Aged , Missouri/epidemiology , Physical Distancing , Quarantine/economics , Quarantine/psychology , SARS-CoV-2/pathogenicity , Stress, Psychological/economics , Stress, Psychological/virology , Substance-Related Disorders/economics , Substance-Related Disorders/psychology , Substance-Related Disorders/virology , Surveys and Questionnaires
17.
Stem Cell Rev Rep ; 17(1): 296-299, 2021 02.
Article in English | MEDLINE | ID: covidwho-1009200

ABSTRACT

We report the case of an HIV-1-infected patient, treated with anti-CD20 monoclonal antibody for a B-cell lymphoma previously treated by autologous stem cell transplant. He suffered from chronic COVID19 and we monitored by plasma SARS-CoV-2 RNA by highly sensitive droplet-based digital PCR technology (ddPCR). Under tocilizumab therapy and despite a first clinical improvement biologically associated with decreasing inflammatory markers, a slight increase of SARS-CoV-2 RNAaemia quantified by ddPCR was highlighted, confirming the absence of viral efficacy of this treatment and predicting the subsequent observed deterioration. As expected, his complete recovery, finally achieved after COVID-19 convalescent plasmatherapy, strictly paralleled plasma SARS-CoV-2 RNA clearance. With these results, we confirmed the interest of SARS-CoV-2 RNAaemia monitoring by ddPCR in COVID-19 patients, particularly during treatment, and firstly showed that this new and specific biomarker could be helpful to select eligible patient for anti-IL6 receptors therapy considering the variable levels of efficacy recently observed with such therapy.


Subject(s)
COVID-19/blood , HIV Infections/blood , Lymphoma, B-Cell/drug therapy , RNA, Viral/blood , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/complications , COVID-19/genetics , COVID-19/virology , HIV Infections/genetics , HIV Infections/therapy , HIV Infections/virology , HIV-1/pathogenicity , Humans , Lymphocytes/virology , Lymphoma, B-Cell/complications , Lymphoma, B-Cell/genetics , Lymphoma, B-Cell/virology , RNA, Viral/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Viral Load/drug effects
18.
AIDS Rev ; 22(4): 227-228, 2020 12 23.
Article in English | MEDLINE | ID: covidwho-1006729

ABSTRACT

The clinical spectrum of "Severe Acute Respiratory Syndrome Coronavirus type 2" (SARS-CoV-2) infection is wider than initially thought. The coronavirus does not establish a chronic cellular infection, in contrast with HIV or the hepatitis B virus, that keeps their genomes, respectively, as proviruses integrated within the chromosomes or as episomes (Soriano et al. J Antimicrob Chemother 2014).


Subject(s)
COVID-19/virology , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , HIV-1/genetics , HIV-1/pathogenicity , Hepatitis B virus/genetics , Hepatitis B virus/pathogenicity , Humans
19.
Biochim Biophys Acta Biomembr ; 1862(7): 183274, 2020 07 01.
Article in English | MEDLINE | ID: covidwho-820155

ABSTRACT

The gp41 type I membrane protein is part of the trimeric Env complex forming the spikes at the HIV surface. By interacting with cellular receptors, the Env protein complex initiates the infectious cycle of HIV. After the first contact has been established Env disassembles by shedding gp120 while the remaining gp41 undergoes a number of conformational changes which drive fusion of the cellular and the viral membranes. Here we investigated the membrane interactions and oligomerization of the two gp41 heptad repeat domains NHR and CHR. While these are thought to form a six-helix bundle in the post-fusion state little is known about their structure and role during prior fusion events. When investigated in aqueous buffer by CD and fluorescence quenching techniques the formation of NHR/CHR hetero-oligomers is detected. An equilibrium of monomers and hetero-oligomers is also observed in membrane environments. Furthermore, the partitioning to POPC or POPC/POPG 3/1 vesicles of the two domains alone or in combination has been studied. The membrane interactions were further characterized by 15N solid-state NMR spectroscopy of uniaxially oriented samples which shows that the polypeptide helices are oriented parallel to the bilayer surface. The 31P solid-state NMR spectra of the same samples are indicative of considerable disordering of the membrane packing. The data support models where NHR and CHR insert in the viral and cellular membranes, respectively, where they exhibit an active role in the membrane fusion events.


Subject(s)
HIV Envelope Protein gp41/ultrastructure , HIV Infections/genetics , HIV-1/genetics , Membrane Fusion/genetics , Cell Membrane/genetics , Cell Membrane/virology , HIV Envelope Protein gp41/chemistry , HIV Envelope Protein gp41/genetics , HIV Infections/virology , HIV-1/pathogenicity , Humans , Magnetic Resonance Spectroscopy , Peptide Fragments/chemistry , Peptide Fragments/genetics , Protein Conformation
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