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Sante Publique (Vandoeuvre-les-Nancy,... 2024Pakistan has the second highest prevalence of hepatitis C globally. The Musafir study, set up in 2018 in a Parisian suburb to understand the representations of hepatitis...
INTRODUCTION
Pakistan has the second highest prevalence of hepatitis C globally. The Musafir study, set up in 2018 in a Parisian suburb to understand the representations of hepatitis and HIV within the Urdu-speaking, male, migrant community living there, provided an opportunity to think about culturally acceptable health promotion interventions. These included awareness campaigns on hepatitis—which did not cover the question of HIV, considered taboo—, held in a mosque.
PURPOSE OF THE RESEARCH
The aim of this article is to describe the implementation of awareness and testing campaigns within a Pakistani religious and cultural association.
METHOD
A partnership with a Pakistani association that runs a place of worship enabled awareness and testing campaigns for hepatitis and HIV to be carried out, thanks to the involvement of the association’s managers and the imam.
RESULTS
Between February and June 2023, 113 people were tested during the five campaigns that were carried out. The population screened consisted almost exclusively of Urdu-speaking men. Anti-HCV antibodies were found in six people, three of whom had already recovered, and two people tested positive for HBV. No cases of HIV were detected.
CONCLUSIONS
The prevalence of hepatitis C found was 5.3 percent, in line with the prevalence in Pakistan. This experiment highlighted the feasibility conditions of a partnership with a faith-based organization and offers ideas for developing this type of initiative in France.
Topics: Humans; Pakistan; Male; Adult; Hepatitis C; Mass Screening; Middle Aged; Young Adult; Female; Prevalence; HIV Infections; Health Promotion; Adolescent
PubMed: 38906813
DOI: No ID Found -
Current Opinion in HIV and AIDS Jul 2023Successful HIV-1 prevention and therapy will require broad and potent coverage of within-host and global viral diversity. Broadly neutralizing antibody (bNAb)... (Review)
Review
PURPOSE OF REVIEW
Successful HIV-1 prevention and therapy will require broad and potent coverage of within-host and global viral diversity. Broadly neutralizing antibody (bNAb) combination and multispecific therapeutics provide an opportunity to meet this challenge due to the complementary activity of individual antibody components. Here, we review the principles and applications of this concept.
RECENT FINDINGS
The Antibody Mediated Prevention (AMP) trials have demonstrated the high bar for neutralization potency and breadth that bNAb-mediated prevention modalities will need to achieve to have a meaningful impact on the HIV-1 epidemic. Additional clinical studies have recently shown that an even higher bar may be required for therapeutic inhibition of the diverse within-host quasispecies present in viremic and aviremic people with HIV-1 (PWH). We discuss how the complementarity of bNAbs in terms of neutralization profiles, resistance mutations and coverage of within-host quasispecies may overcome these stringent requirements and lead to effective bNAb combination or multispecific antibody based prophylactic and therapeutic strategies.
SUMMARY
The design of next-generation bNAb-based combination or multispecific therapeutics for the prevention and/or treatment of HIV-1 infection will need to leverage the complementarity of component bNAbs to maximize the potency and breadth that will be required for clinical success.
Topics: Humans; HIV Infections; Broadly Neutralizing Antibodies; HIV Antibodies; HIV-1; Antibodies, Neutralizing
PubMed: 37249911
DOI: 10.1097/COH.0000000000000800 -
Cell Host & Microbe Aug 2023HIV-1 broadly neutralizing antibodies (bNAbs) can decrease viremia but are usually unable to counteract autologous viruses escaping the antibody pressure. Nonetheless,...
HIV-1 broadly neutralizing antibodies (bNAbs) can decrease viremia but are usually unable to counteract autologous viruses escaping the antibody pressure. Nonetheless, bNAbs may contribute to natural HIV-1 control in individuals off antiretroviral therapy (ART). Here, we describe a bNAb B cell lineage elicited in a post-treatment controller (PTC) that exhibits broad seroneutralization and show that a representative antibody from this lineage, EPTC112, targets a quaternary epitope in the glycan-V3 loop supersite of the HIV-1 envelope glycoprotein. The cryo-EM structure of EPTC112 complexed with soluble BG505 SOSIP.664 envelope trimers revealed interactions with N301- and N156-branched N-glycans and the GDIR V3 loop motif. Although the sole contemporaneous virus circulating in this PTC was resistant to EPTC112, it was potently neutralized by autologous plasma IgG antibodies. Our findings illuminate how cross-neutralizing antibodies can alter the HIV-1 infection course in PTCs and may control viremia off-ART, supporting their role in functional HIV-1 cure strategies.
Topics: Humans; Broadly Neutralizing Antibodies; HIV Antibodies; HIV-1; Antibodies, Neutralizing; Viremia; HIV Infections; Antigens, Viral; Polysaccharides; env Gene Products, Human Immunodeficiency Virus
PubMed: 37433296
DOI: 10.1016/j.chom.2023.06.006 -
Cell Reports Jul 2023Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with...
Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers eliciting autologous neutralizing antibodies has been reported in multiple vaccine-test species, though not in humans. To investigate elicitation of HIV-1 neutralizing antibodies in humans, here, we analyze B cells from a phase I clinical trial of the "DS-SOSIP"-stabilized envelope trimer from strain BG505, identifying two antibodies, N751-2C06.01 and N751-2C09.01 (named for donor-lineage.clone), that neutralize the autologous tier-2 strain, BG505. Though derived from distinct lineages, these antibodies form a reproducible antibody class that targets the HIV-1 fusion peptide. Both antibodies are highly strain specific, which we attribute to their partial recognition of a BG505-specific glycan hole and to their binding requirements for a few BG505-specific residues. Prefusion-stabilized envelope trimers can thus elicit autologous tier-2 neutralizing antibodies in humans, with initially identified neutralizing antibodies recognizing the fusion-peptide site of vulnerability.
Topics: Humans; AIDS Vaccines; Antibodies, Neutralizing; env Gene Products, Human Immunodeficiency Virus; HIV Antibodies; HIV Infections; HIV Seropositivity; HIV-1; Peptides
PubMed: 37436899
DOI: 10.1016/j.celrep.2023.112755 -
Science Translational Medicine Jul 2023Broadly neutralizing antibodies (bNAbs) may provide an alternative to standard antiretroviral treatment (ART) for controlling HIV-1 replication and may have... (Clinical Trial)
Clinical Trial
Broadly neutralizing antibodies (bNAbs) may provide an alternative to standard antiretroviral treatment (ART) for controlling HIV-1 replication and may have immunotherapeutic effects against HIV-1 reservoirs. We conducted a prospective clinical trial with two HIV-1 bNAbs (VRC01LS and 10-1074) in children ( = 25) who had previously initiated small-molecule ART treatment before 7 days of age and who continued treatment for at least 96 weeks. Both bNAbs were dosed intravenously every 4 weeks, overlapping with ART for at least 8 weeks and then continued for up to 24 weeks or until detectable viremia of HIV-1 RNA rose above 400 copies per milliliter in the absence of ART. Eleven (44%) children maintained HIV-1 RNA below 400 copies per milliliter through 24 weeks of bNAb-only treatment; 14 (56%) had detectable viremia above 400 copies per milliliter at a median of 4 weeks. Archived HIV-1 provirus susceptible to 10-1074, lower birth HIV-1 DNA reservoir in peripheral blood mononuclear cells, sustained viral suppression throughout early life, and combined negative qualitative HIV-1 DNA polymerase chain reaction and negative HIV-1 serology at entry were associated with maintaining suppression on bNAbs alone. This proof-of-concept study suggests that bNAbs may represent a promising treatment modality for infants and children living with HIV-1. Future studies using newer bNAb combinations with greater breadth and potency are warranted.
Topics: Child; Humans; Anti-Retroviral Agents; Antibodies, Neutralizing; Botswana; Broadly Neutralizing Antibodies; HIV Antibodies; HIV Infections; HIV-1; Leukocytes, Mononuclear; Prospective Studies; Viremia
PubMed: 37406137
DOI: 10.1126/scitranslmed.adh0004 -
Current Opinion in HIV and AIDS Nov 2023There is growing consensus that eliciting CD8 + T cells in addition to antibodies may be required for an effective HIV vaccine for both prevention and cure. Here, we... (Review)
Review
PURPOSE OF REVIEW
There is growing consensus that eliciting CD8 + T cells in addition to antibodies may be required for an effective HIV vaccine for both prevention and cure. Here, we review key qualities of vaccine-elicited CD8 + T cells as well as major CD8 + T cell-based delivery platforms used in recent HIV vaccine clinical trials.
RECENT FINDINGS
Much progress has been made in improving HIV immunogen design and delivery platforms to optimize CD8 + T cell responses. With regards to viral vectors, recent trials have tested newer chimp and human adenovirus vectors as well as a CMV vector. DNA vaccine immunogenicity has been increased by delivering the vaccines by electroporation and together with adjuvants as well as administering them as part of a heterologous regimen. In preclinical models, self-amplifying RNA vaccines can generate durable tissue-based CD8 + T cells. While it may be beneficial for HIV vaccines to recapitulate the functional and phenotypic features of HIV-specific CD8 + T cells isolated from elite controllers, most of these features are not routinely measured in HIV vaccine clinical trials.
SUMMARY
Identifying a vaccine capable of generating durable T cell responses that target mutationally vulnerable epitopes and that can rapidly intercept infecting or rebounding virus remains a challenge for HIV. Comprehensive assessment of HIV vaccine-elicited CD8 + T cells, as well as comparisons between different vaccine platforms, will be critical to advance our understanding of how to design better CD8 + T cell-based vaccines for HIV.
Topics: Humans; AIDS Vaccines; HIV Infections; CD8-Positive T-Lymphocytes; Genetic Vectors; Epitopes
PubMed: 37751362
DOI: 10.1097/COH.0000000000000824 -
Frontiers in Pharmacology 2023The human immunodeficiency virus (HIV) persists in latently infected CD4T cells and integrates with the host genome until cell death. Acquired immunodeficiency syndrome... (Review)
Review
The human immunodeficiency virus (HIV) persists in latently infected CD4T cells and integrates with the host genome until cell death. Acquired immunodeficiency syndrome (AIDS) is associated with HIV-1. Possibly, treating HIV/AIDS is an essential but challenging clinical goal. This review provides a detailed account of the types and mechanisms of monotherapy and combination therapy against HIV-1 and describes nanoparticle and hydrogel delivery systems. In particular, the recently developed capsid inhibitor (Lenacapavir) and the Ainuovirine/tenofovir disoproxil fumarate/lamivudine combination (ACC008) are described. It is interestingly to note that the lack of the multipass transmembrane proteins serine incorporator 3 (SERINC3) and the multipass transmembrane proteins serine incorporator 5 (SERINC5) may be one of the reasons for the enhanced infectivity of HIV-1. This discovery of SERINC3 and SERINC5 provides new ideas for HIV-1 medication development. Therefore, we believe that in treating AIDS, antiviral medications should be rationally selected for pre-exposure and post-exposure prophylaxis to avoid the emergence of drug resistance. Attention should be paid to the research and development of new drugs to predict HIV mutations as accurately as possible and to develop immune antibodies to provide multiple guarantees for the cure of AIDS.
PubMed: 37954841
DOI: 10.3389/fphar.2023.1294966 -
Nature Medicine Oct 2023The main barrier to HIV cure is a persistent reservoir of latently infected CD4 T cells harboring replication-competent provirus that fuels rebound viremia upon...
The main barrier to HIV cure is a persistent reservoir of latently infected CD4 T cells harboring replication-competent provirus that fuels rebound viremia upon antiretroviral therapy (ART) interruption. A leading approach to target this reservoir involves agents that reactivate latent HIV proviruses followed by direct clearance of cells expressing induced viral antigens by immune effector cells and immunotherapeutics. We previously showed that AZD5582, an antagonist of inhibitor of apoptosis proteins and mimetic of the second mitochondrial-derived activator of caspases (IAPi/SMACm), induces systemic reversal of HIV/SIV latency but with no reduction in size of the viral reservoir. In this study, we investigated the effects of AZD5582 in combination with four SIV Env-specific Rhesus monoclonal antibodies (RhmAbs) ± N-803 (an IL-15 superagonist) in SIV-infected, ART-suppressed rhesus macaques. Here we confirm the efficacy of AZD5582 in inducing SIV reactivation, demonstrate enhancement of latency reversal when AZD5582 is used in combination with N-803 and show a reduction in total and replication-competent SIV-DNA in lymph-node-derived CD4 T cells in macaques treated with AZD5582 + RhmAbs. Further exploration of this therapeutic approach may contribute to the goal of achieving an HIV cure.
Topics: Animals; HIV Infections; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Macaca mulatta; Anti-Retroviral Agents; Virus Latency; Virus Replication; HIV-1; Antibodies; Lymph Nodes; CD4-Positive T-Lymphocytes; Viral Load
PubMed: 37783968
DOI: 10.1038/s41591-023-02570-7 -
Journal of the Peripheral Nervous... Dec 2023The frequency of nodal-paranodal antibodies in HIV-infected patients with chronic immune-mediated radiculo-neuropathies (IMRN) has not been previously described.
BACKGROUND
The frequency of nodal-paranodal antibodies in HIV-infected patients with chronic immune-mediated radiculo-neuropathies (IMRN) has not been previously described.
METHODS
HIV-infected patients who met the inclusion criteria for chronic IMRN were screened for immunoglobulin G (IgG) antibodies directed against nodal (neurofascin (NF)186) and paranodal (NF155, contactin-1 (CNTN1) and contactin-associated protein(Caspr1)) cell adhesion molecules, using a live, cell-based assay. To explore potential pathogenicity, binding of human IgG to myelinated co-cultures was assessed by incubation with patients' sera positive for nodal or paranodal antibodies. Normal human serum was added as a source of complement to assess for complement activation as a mechanism for myelin injury.
RESULTS
Twenty-four HIV-infected patients with IMRN were included in the study, 15 with chronic inflammatory demyelinating polyneuropathy (CIDP), 4 with ventral root radiculopathies (VRR), and 5 with dorsal root ganglionopathies (DRG). Five patients with CIDP had combined central and peripheral demyelination (CCPD). Three patients (12.7%) tested positive for neurofascin IgG1 antibodies in the following categories: 1 patient with VRR was NF186 positive, and 2 patients were NF155 positive with DRG and mixed sensory-motor demyelinating neuropathy with optic neuritis, respectively.
CONCLUSION
The frequency of nodal-paranodal antibodies is similar among IMRN regardless of HIV status. Interpretation of the results in the context of HIV is challenging as there is uncertainty regarding pathogenicity of the antibodies, especially at low titres. Larger prospective immune studies are required to delineate pathogenicity in the context of HIV, and to establish a panel of antibodies to predict for a particular clinical phenotype.
Topics: Humans; Autoantibodies; Nerve Growth Factors; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Prospective Studies; Immunoglobulin G; Contactin 1; HIV Infections
PubMed: 37676746
DOI: 10.1111/jns.12596 -
Nature Nov 2023Human immunodeficiency virus 1 (HIV-1) infection is initiated by binding of the viral envelope glycoprotein (Env) to the cell-surface receptor CD4. Although...
Human immunodeficiency virus 1 (HIV-1) infection is initiated by binding of the viral envelope glycoprotein (Env) to the cell-surface receptor CD4. Although high-resolution structures of Env in a complex with the soluble domains of CD4 have been determined, the binding process is less understood in native membranes. Here we used cryo-electron tomography to monitor Env-CD4 interactions at the membrane-membrane interfaces formed between HIV-1 and CD4-presenting virus-like particles. Env-CD4 complexes organized into clusters and rings, bringing the opposing membranes closer together. Env-CD4 clustering was dependent on capsid maturation. Subtomogram averaging and classification revealed that Env bound to one, two and finally three CD4 molecules, after which Env adopted an open state. Our data indicate that asymmetric HIV-1 Env trimers bound to one and two CD4 molecules are detectable intermediates during virus binding to host cell membranes, which probably has consequences for antibody-mediated immune responses and vaccine immunogen design.
Topics: Humans; AIDS Vaccines; Capsid; CD4 Antigens; Cell Membrane; Cryoelectron Microscopy; Electron Microscope Tomography; HIV Antibodies; HIV Envelope Protein gp120; HIV Infections; HIV-1; Protein Multimerization; Virion
PubMed: 37993716
DOI: 10.1038/s41586-023-06762-6