Acceptance and Factors Associated With Participation in Functional Cure–Related Trials Among People Living With HIV: A Cross-sectional Study in Southern China

HIV remains a global health challenge,and research efforts directed towards a functional cure require people living with HIV(PLHIV)in-volvement in clinical trials.Our study assessed willingness to participate in HIV functional cure–related clinical trials and associated fac-tors among PLHIV in Guangzhou,China,using a questionnaire survey approach.We analyzed responses from 718 questionnaires,finding that 71.2%were willing to participate in Phase Ⅲtrials,while 51.7%were willing to participate in Phase I trials and 42.9%expressed acceptability for analytic treatment interruption.Multivariate logistic regression demonstrated that male PLHIV,those with awareness of functional cure,and PLHIV,who had been on antiretroviral therapy(ART)for less than 1 year,were more willing to partic-ipate in Phase Ⅲtrials.Those with a body mass index greater than 24,and those without resistance to ART drug were more willing to participate in Phase I trials.The major motivations for participation in Phase Ⅲtrials were access to cutting-edge treatments(62.6%)and supporting research(55.3%).Safety was the main concern contributing to hesitancy.Our study revealed a high willingness to participate in HIV functional cure–related trials among PLHIV in Guangzhou,China,and willingness varied across different trial phases and was in-fluenced by multiple factors.This study provides valuable references for future clinical trial recruitment strategies and public health policy formulation.

Safety and Immunogenicity of SARS-CoV-2 Vaccines in People Living With HIV:A Systematic Review and Meta-analysis of Real-World Studies

The safety and immunogenicity of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccines in people living with HIV(PLWH)in real-world studies remain controversial.Thus,we conducted a comprehensive systematic review and meta-analysis to address this issue.Data search were conducted from PubMed,Web of Science and EMBASE.Adverse events following vaccination,the risk ratio(RR)of SARS-CoV-2–specific IgG seroconversion and the level of anti–SARS-CoV-2 neutralizing antibodies were compared between the PLWH group and a healthy control group.A total of 10,582 PLWH from 22 studies were included.In our analysis,the incidence of local or systemic adverse events after the first SARS-CoV-2 vaccine dose was not statistically different between PLWH and healthy controls.However,there was a statistical difference after the second dose(RR,0.83;95%CI,0.71–0.98).The seroconversion rate of SARS-CoV-2 IgGantibodies in PLWH was significantly lower than that in the healthy control group(RR,0.94;95%CI,0.89–0.98;I2=80%,P<0.01).The anti–SARS-CoV-2 neutralizing antibody titers in PLWH after full immunization were also significantly lower than those in the healthy control group(RR,0.91;95%CI,0.85–0.98;I2=81%,P<0.01).The safety and tolerance of COVID-19 vaccines in PLWHare acceptable.However,their immunogenicitymay be impaired to a certain extent,characterized by a lower IgGseroconversion rate and neutralizing antibody titers compared with healthy individuals.These findings should provide guidance for optimizing future COVID-19 vaccination strategies among PLWH.

B cell engineering in vivo:Accelerating induction of broadly neutralizing antibodies against HIV-1 infection

In a recent study published in Nature Biotechnology,1 Nahmad and colleagues reported in vivo B-cell engineering to generate broadly neutralizing antibodies(bnAbs)against human immunodeficiency virus type 1(HIV-1)in mice.This proof-of-concept study suggests the possibility of in vivo B-cell engineering as a novel preventive or therapeutic approach against HIV-1 infection.

First clinical study of germline-targeting strategy: One step closer to a successful bnAb-based HIV vaccine

The epidemic of human immunodeficiency virus type 1(HIV-1)remains amajor threat to global public health,with approximately 38 million people living with HIV-1 worldwide.However,a prophylactic vaccine against HIV-1 is not available yet.In a recent study,1 Leggat and colleagues reported the first-in-human test of a germline-targeting HIV-1 vaccine candidate,eOD-GT860-mer adjuvanted with AS01B.Encouragingly,this strategy effectively activated the B cell precursors(germlines)of VRC01-class broadly neutralizing antibodies(bnAbs)in 97%(35 of 36)of vaccine recipients.

Safety of SARS-CoV-2 vaccines:a systematic review and meta-analysis of randomized controlled trials

Background Various modalities of vaccines against coronavirus disease 2019(COVID-19),based on different platforms and immunization procedures,have been successively approved for marketing worldwide.A comprehensive review for clinical trials assessing the safety of COVID-19 vaccines is urgently needed to make an accurate judgment for mass vaccination.Main text A systematic review and meta-analysis was conducted to determine the safety of COVID-19 vaccine candidates in randomized controlled trials(RCTs).Data search was performed in PubMed,Embase,Cochrane library,Scopus,Web of Science,and MedRxiv.Included articles were limited to RCTs on COVID-19 vaccines.A total of 73,633 subjects from 14 articles were included to compare the risks of adverse events following immunization(AEFI)after vaccinating different COVID-19 vaccines.Pooled risk ratios(RR)of total AEFI for inactivated vaccine,viral-vectored vaccine,and mRNA vaccine were 1.34[95%confidence interval(CI)1.11–1.61,P<0.001],1.65(95%CI 1.31–2.07,P<0.001),and 2.01(95%CI 1.78–2.26,P<0.001),respectively.No significant differences on local and systemic AEFI were found between the first dose and second dose.In addition,people aged≤55 years were at significantly higher risk of AEFI than people aged≥56 years,with a pooled RR of 1.25(95%CI 1.15–1.35,P<0.001).Conclusions The safety and tolerance of current COVID-19 vaccine candidates are acceptable for mass vaccination,with inactivated COVID-19 vaccines candidates having the lowest reported AEFI.Long-term surveillance of vaccine safety is required,especially among elderly people with underlying medical conditions.

Modulation of Antiviral Immunity and Therapeutic Efficacy by 25-Hydroxycholesterol in Chronically SIV-Infected, ART-Treated Rhesus Macaques

Cholesterol-25-hydroxylase(CH25 H)and its enzymatic product 25-hydroxy cholesterol(25 HC)exert broadly antiviral activity including inhibiting HIV-1 infection.However,their antiviral immunity and therapeutic efficacy in a nonhuman primate model are unknown.Here,we report that the regimen of 25 HC combined with antiretroviral therapy(ART),provides profound immunological modulation towards inhibiting viral replication in chronically SIVmac239-infected rhesus macaques(RMs).Compared to the ART alone,this regimen more effectively controlled SIV replication,enhanced SIVspecific cellular immune responses,restored the ratio of CD4/CD8 cells,reversed the hyperactivation state of CD4^(+)T cells,and inhibited the secretion of proinflammatory cytokines by CD4^(^(+))and CD8^(+)T lymphocytes in chronically SIVinfected RMs.Furthermore,the in vivo safety and the preliminary pharmacokinetics of the 25 HC compound were assessed in this RM model.Taken together,these assessments help explain the profound relationship between cholesterol metabolism,immune modulation,and antiviral activities by 25 HC.These results provide insight for developing novel therapeutic drug candidates against HIV-1 infection and other related diseases.

Antibody upstream sequence diversity and its biological implications revealed by repertoire sequencing

The sequence upstream of the antibody variable region(antibody upstream sequence[AUS])consists of a 5′untranslated region(5′UTR)and a preceding leader region.The sequence variations in AUS affect antibody engineering and PCR based antibody quantification and may also be implicated in mRNA transcription and translation.However,the diversity of AUSs remains elusive.Using 5′rapid amplification of cDNA ends and high-throughput antibody repertoire sequencing technique,we acquired full-length AUSs for human,rhesus macaque,cynomolgus macaque,mouse,and rat.We designed a bioinformatics pipeline and identified 3307 unique AUSs,corresponding to 3026 and 1457 unique sequences for 5′UTR and leader region,respectively.Comparative analysis indicated that 928(63.69%)leader sequences are novel relative to those recorded in the international ImMunoGeneTics information system.Evolutionarily,leader sequences are more conserved than 5′UTR and seem to coevolve with their downstream V genes.Besides,single-nucleotide polymorphisms are position dependent for leader regions and may contribute to the functional reversal of the downstream V genes.Finally,the AUGs in AUSs were found to have little impact on gene expression.Taken together,our findings can facilitate primer design for capturing antibodies efficiently and provide a valuable resource for antibody engineering and molecule-level antibody studies.