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Background: Reemergence of human herpesvirus 8 (HHV-8)-induced Kaposi sarcoma (KS) in people living with HIV (PLWH) despite antiretroviral therapy (ART) poses a clinical challenge because they already have favorable CD4 T-cell numbers and undetectable viral loads. We observed that clinical presentation in PLWH on ART resembled classic KS found in older HIV-uninfected patients and hypothesized that immunosenescence may thus play a role in occurrence of KS on ART. We compared viral and immune factors implicated in the development of KS in ART-treated PLWH (HIV KS) and HIV-uninfected classic KS patients (cKS), compared to controls without KS (HIV Control, cControls respectively). Methods: Plasma, peripheral blood mononuclear cell, and skin tissues were obtained from 11 HIV KS and 11 cKS patients and 2 groups of age-matched controls. Results: HIV KS participants were younger than cKS (aged 53 vs 75 years). HHV-8 genotypes did not differ between groups. Despite the younger age and a lower CD4/CD8 ratio, activated, exhausted, and senescent T-cell frequencies were similar between HIV KS and cKS. Anti-HHV-8 immunoglobulin G levels were higher and circulating HHV-8 DNA lower in HIV KS compared with cKS. Circulating platelet-derived growth factors AA-BB and granulocyte colony-stimulating factors were higher in HIV KS We observed similar levels of HHV-8 DNA and PD-1 expression in skin lesions from HIV KS and cKS patients. Conclusions: Altogether, early immune senescence could be involved in the development of KS in ART-treated PLWH. Higher anti-HHV-8 immunoglobulin G levels could be linked with lower circulating viral load. Such insights should help developing therapeutical strategies to prevent development and treat KS in PLWH on ART.
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BACKGROUND: Doravirine is the latest NNRTI to be approved for the treatment of HIV-1 and has a different resistance profile from first-generation NNRTIs. Our aim was to investigate the virological efficacy of antiretroviral treatment including doravirine in people living with HIV-1 (PLWHIV), the factors associated with virological failure (VF) and those associated with the emergence of reverse transcriptase (RT) mutations in the case of VF. METHODS: A retrospective national survey of PLWHIV who were either naive or experienced on antiretroviral treatment including doravirine was conducted. VF was defined as two consecutive plasma viral loads (VLs) of ≥50â copies/mL or one VL of ≥200â copies/mL. Genotypic resistance tests were interpreted using the Stanford (v9.4.1) and ANRS (v33) algorithms. RESULTS: Of the 589 PLWHIV treated with a doravirine-containing regimen, 8.5% were naive and 91.5% had prior antiretroviral experience; 56.9% were infected with HIV-1 B subtype. Overall, 88.3% and 85.1% of participants were virologically controlled at Month (M)3 and M6 of doravirine treatment, respectively. In multivariable analysis, CRF02_AG subtype, higher zenith plasma HIV-1 RNA VL, doravirine initiation in the context of failure and baseline V179D mutation presence were associated with VF. Among 88 PLWHIV who experienced virological failure at M6, 15.9% had a median of 2 (IQR 1-3) HIV RT mutations. In multivariable analysis, the only factor associated with the occurrence of mutations was a genotypic sensitivity score that was not fully sensitive. CONCLUSIONS: This study is one of the largest to characterize the virological efficacy of doravirine-containing regimens in clinical practice and to identify factors associated with VF or emergence of resistance mutations that should be considered in clinical management.
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Fármacos Anti-HIV , Farmacorresistência Viral , Infecções por HIV , HIV-1 , Piridonas , Triazóis , Carga Viral , Humanos , HIV-1/genética , HIV-1/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Piridonas/uso terapêutico , Masculino , Feminino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Carga Viral/efeitos dos fármacos , França , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Triazóis/uso terapêutico , Genótipo , Mutação , Transcriptase Reversa do HIV/genética , Terapia Antirretroviral de Alta Atividade , Resultado do TratamentoRESUMO
OBJECTIVES: Resistance associated mutations (RAMs) are archived in the HIV reservoir and can re-emerge with an inappropriate ART use limiting treatment options. However, recent studies, using ultra-deep sequencing (UDS), showed a decrease of quasispecies harbouring RAMs, suggesting that recycling some antiretrovirals could be considered. The aim of this study was to characterize, in HIV treated PLWHIV, the M184V mutation decrease kinetics in proviral DNA and associated factors of M184V mutation clearance over time. METHODS: UDS was performed on HIV-DNA from blood cells at different time points to quantify the percentage of M184V positive quasispecies. The sequence reads were analysed with a minimum coverage set at 50 and an ambiguity filter at 5% or 2%. RESULTS: At 2.5â years after the first time point, the M184V lost was observed in 50% of PLWHIV. Moreover, univariate analyses highlight that a higher nadir CD4 count and a lower zenith HIV1 RNA viral load were correlated with a faster clearance of the mutation. In multivariate analysis, a higher zenith was negatively associated with the M184V clearance at the 5% threshold. Interestingly, lamivudine/emtricitabine presence in the ART therapy regiment during the 5 years was not associated with the persistence of the M184V. CONCLUSIONS: Our study provides new information concerning the clearance speed of M184V mutation over time in PLWHIV with fully suppressed viremia, opens the discussion about the duration needed to consider a lamivudine/emtricitabine recycling and reinforces the association of the nadir and zenith values with the M184V mutation clearance.
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Fármacos Anti-HIV , Farmacorresistência Viral , Infecções por HIV , HIV-1 , Mutação , Carga Viral , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Farmacorresistência Viral/genética , HIV-1/genética , HIV-1/efeitos dos fármacos , Contagem de Linfócito CD4 , Masculino , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacologia , Feminino , Adulto , Pessoa de Meia-Idade , Provírus/genética , Sequenciamento de Nucleotídeos em Larga Escala , DNA Viral/genética , DNA Viral/sangue , Transcriptase Reversa do HIV/genética , Terapia Antirretroviral de Alta AtividadeRESUMO
Introduction: XAV-19 is a glyco-humanized swine polyclonal antibody targeting SARS-CoV-2 with high neutralizing activity. The safety and clinical efficacy of XAV-19 were investigated in patients with mild to moderate COVID-19. Methods: This phase II/III, multicentric, randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety and clinical efficacy of XAV-19 in patients with a seven-point WHO score of 2 to 4 at randomization, i.e., inpatients with COVID-19 requiring or not requiring low-flow oxygen therapy, and outpatients not requiring oxygen (EUROXAV trial, NCT04928430). Adult patients presenting in specialized or emergency units with confirmed COVID-19 and giving their consent to participate in the study were randomized to receive 150 mg of XAV-19 or placebo. The primary endpoint was the proportion of patients with aggravation within 8 days after treatment, defined as a worsening of the seven-point WHO score of at least one point between day 8 and day 1 (inclusion). The neutralization activity of XAV-19 against variants circulating during the trial was tested in parallel. Results: From March 2021 to October 2022, 279 patients received either XAV-19 (N = 140) or placebo (N = 139). A slow enrollment and a low rate of events forced the termination of the premature trial. XAV-19 was well tolerated. Underpowered statistics did not allow the detection of any difference in the primary endpoint between the two groups or in stratified groups. Interestingly, analysis of the time to improvement (secondary endpoint) showed that XAV-19 significantly accelerated the recovery for patients with a WHO score of 2 or 3 (median at 7 days vs. 14 days, p = 0.0159), and even more for patients with a WHO score of 2 (4 days vs. 14 days, p = 0.0003). The neutralizing activity against Omicron and BA.2, BA.2.12.1, BA.4/5, and BQ.1.1 subvariants was shown. Discussion: In this randomized placebo- controlled trial with premature termination, reduction of aggravation by XAV-19 at day 8 in patients with COVID-19 was not detectable. However, a significant reduction of the time to improvement for patients not requiring oxygen was observed. XAV-19 maintained a neutralizing activity against SARS-CoV-2 variants. Altogether, these data support a possible therapeutic interest for patients with mild to moderate COVID-19 requiring anti-SARS-CoV-2 neutralizing antibodies. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT04928430; https://www.clinicaltrialsregister.eu/about.html (EudraCT), identifier 2020-005979-12.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , COVID-19/imunologia , COVID-19/terapia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/uso terapêutico , Método Duplo-Cego , Idoso , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Adulto , Resultado do Tratamento , Índice de Gravidade de DoençaRESUMO
Background: Surveillance of SARS-CoV-2 variants of concern (VOCs) and lineages is crucial for decision-making. Our objective was to study the SARS-CoV-2 clade dynamics across epidemiological waves and evaluate the reliability of SNPsig® SARS-CoV-2 EscapePLEX CE in detecting VOCs in Cameroon. Material and methods: A laboratory-based study was conducted on SARS-CoV-2 positive nasopharyngeal specimens cycle threshold (Ct)≤30 at the Chantal BIYA International Reference Centre in Yaoundé-Cameroon, between April-2020 to August-2022. Samples were analyzed in parallel with Sanger sequencing and (SNPsig® SARS-CoV-2 EscapePLEX CE), and performance characteristics were evaluated by Cohen's coefficient and McNemar test. Results: Of the 130 sequences generated, SARS-CoV-2 clades during wave-1 (April-November 2020) showed 97 % (30/31) wild-type lineages and 3 % (1/31) Gamma-variant; wave-2 (December-2020 to May-2021), 25 % (4/16) Alpha-variant, 25 % (4/16) Beta-variant, 44 % (7/16) wild-type and 6 % (1/16) mu; wave-3 (June-October 2021), 94 % (27/29) Delta-variant, 3 % (1/29) Alpha-variant, 3 % (1/29) wild-type; wave-4 (November-2021 to August-2022), 98 % (53/54) Omicron-variant and 2 % (1/54) Delta-variant. Omicron sub-variants were BA.1 (47 %), BA.5 (34 %), BA.2 (13 %) and BA.4 (6 %). Globally, the two genotyping methods accurately identified the SARS-CoV-2 VOCs (P = 0.17, McNemar test; Ka = 0.67). Conclusion: Genomic surveillance reveals a rapid dynamic in SARS-CoV-2 strains between epidemiological waves in Cameroon. For wide-spread variant surveillance in resource-limited settings, SNPsig® SARS-CoV-2 EscapePLEX CEkit represents a suitable tool, pending upgrading for distinguishing Omicron sub-lineages.
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Introduction: Initiation of antiretroviral treatment (ART) in patients early after HIV-infection and long-term suppression leads to low or undetectable levels of HIV RNA and cell-associated (CA) HIV DNA and RNA. Both CA-DNA and CA-RNA, overestimate the size of the HIV reservoir but CA-RNA as well as p24/cell-free viral RNA can be indicators of residual viral replication. This study describes HIV RNA amounts and levels of cytokines/soluble markers in 40 well-suppressed adolescents who initiated ART early in life and investigated which viral markers may be informative as endpoints in cure clinical trials within this population. Methods: Forty adolescents perinatally infected with HIV on suppressive ART for >5 years were enrolled in the CARMA study. HIV DNA and total or unspliced CA-RNA in PBMCs were analyzed by qPCR/RT-qPCR and dPCR/RT-dPCR. Cell-free HIV was determined using an ultrasensitive viral load (US-VL) assay. Plasma markers and p24 were analyzed by digital ELISA and correlations between total and unspliced HIV RNA and clinical markers, including age at ART, Western Blot score, levels of cytokines/inflammation markers or HIV CA-DNA, were tested. Results: CA-RNA was detected in two thirds of the participants and was comparable in RT-qPCR and RT-dPCR. Adolescents with undetectable CA-RNA showed significantly lower HIV DNA compared to individuals with detectable CA-RNA. Undetectable unspliced CA-RNA was positively associated with age at ART initiation and Western Blot score. We found that a higher concentration of TNF-α was predictive of higher CA-DNA and CA-RNA. Other clinical characteristics like US-VL, time to suppression, or percent CD4+ T-lymphocytes were not predictive of the CA-RNA in this cross-sectional study. Conclusions: Low CA-DNA after long-term suppressive ART is associated with lower CA-RNA, in concordance with other reports. Patients with low CA-RNA levels in combination with low CA-DNA and low Western Blot scores should be further investigated to characterize candidates for treatment interruption trials. Unspliced CA-RNA warrants further investigation as a marker that can be prioritized in paediatric clinical trials where the sample volume can be a significant limitation.
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Ácidos Nucleicos Livres , Infecções por HIV , Humanos , Adolescente , Criança , Estudos Transversais , RNA , Antirretrovirais/uso terapêutico , Citocinas , Infecções por HIV/tratamento farmacológico , DNARESUMO
OBJECTIVES: As many disparities in the clinical use of HIV DNA sequencing are observed, a DELPHI-type consensus was initiated in France to homogenize use, techniques and interpretation of results. METHODS: Based on a literature review and clinical experience, a steering committee (SC) of eight virologists and one infectious disease specialist formulated statements. Statements were submitted to an independent and anonymous electronic vote of virologists and HIV clinicians in France, between October 2022 and December 2022. RESULTS: The SC developed 20 statements grouped into six categories: clinical situations for the use of HIV DNA genotyping; techniques for performing HIV DNA genotyping; consideration of apolipoprotein B mRNA editing enzyme (APOBEC) mutations; genotyping results reporting; recycling of antiretrovirals; and availability of HIV DNA genotyping tests and delays. Twenty-one virologists and 47 clinicians participated in two voting rounds and 18/20 (90%) assertions reached a 'strong' consensus. For example, that prior genotyping on HIV DNA is useful for clinical decision-making when considering switching to some long-acting regimens or to reduce the number of antiretroviral agents in virologically suppressed patients for whom RNA data are unavailable/not exploitable/not sufficiently informative. Two statements achieved no consensus: reporting any detected viral minority population for discussion in multidisciplinary meetings (virologists), and possible risk of virological failure when using a second-generation InSTI plus lamivudine or emtricitabine regimen in patients with undetectable viral load within ≥1â year and in the presence of a documented M184V mutation within the last 5â years (clinicians). CONCLUSIONS: This DELPHI-type consensus will facilitate the strengthening and harmonization of good practice when performing HIV DNA sequencing.
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Fármacos Anti-HIV , Infecções por HIV , Humanos , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Consenso , DNA/uso terapêutico , Genótipo , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológicoRESUMO
BACKGROUND: Limited data are available regarding the susceptibility of the reverse transcriptase V106 polymorphism to doravirine. METHODS: Doravirine susceptibility was measured in site-directed mutants (SDMs) containing V106I, V106A, V106M, and Y188L mutations in subtype B (NL4-3, HXB2) and CRF02_AG background and in recombinant viruses with RT harboring V106I alone derived from 50 people with HIV. RESULTS: HIV-1 B subtype was detected in 1523 of 2705 cases. Prevalence of V106I was 3.2% in B and 2.5% in non-B subtypes, and was higher in subtype F (8.1%) and D (14.3%). Fold-changes (FC) in susceptibility for SDMs were below doravirine biological cutoff (3.0) for V106I, but not for V106A, V106M, and Y188L. Clinically derived viruses tested included 22 B (median FC, 1.2; interquartile range [IQR], 0.9-1.6) and 28 non-B subtypes (median FC, 1.8; IQR, 0.9-3.0). Nine (18%) viruses showed FC values equal or higher than the doravirine biological FC cutoff. CONCLUSIONS: The prevalence of the HIV-1 RT V106I polymorphism in MeditRes HIV consortium remains low, but significantly more prevalent in subtypes D and F. V106I minimally decreased the susceptibility to doravirine in SDMs and most clinical isolates. Reduced susceptibility seems to occur at increased frequency in subtype F1; however, the clinical impact remains to be investigated. CLINICAL TRIALS REGISTRATION: NCT04894357.
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Fármacos Anti-HIV , Farmacorresistência Viral , Infecções por HIV , Transcriptase Reversa do HIV , HIV-1 , Piridonas , Triazóis , Humanos , HIV-1/genética , HIV-1/efeitos dos fármacos , HIV-1/classificação , HIV-1/enzimologia , Transcriptase Reversa do HIV/genética , Infecções por HIV/virologia , Infecções por HIV/epidemiologia , Piridonas/farmacologia , Farmacorresistência Viral/genética , Fármacos Anti-HIV/farmacologia , Triazóis/farmacologia , Polimorfismo Genético , Prevalência , Masculino , Feminino , Inibidores da Transcriptase Reversa/farmacologia , Adulto , Genótipo , Fenótipo , Pessoa de Meia-IdadeAssuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Feminino , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Papillomavirus Humano , Esquemas de Imunização , Pandemias/prevenção & controle , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , VacinaçãoAssuntos
Fármacos Anti-HIV , Infecções por HIV , Inibidores de Integrase de HIV , Integrase de HIV , HIV-1 , Humanos , HIV-1/genética , Transcrição Reversa , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Inibidores de Integrase de HIV/farmacologia , Inibidores de Integrase de HIV/uso terapêutico , Compostos Heterocíclicos com 1 Anel , Mutação , Integrase de HIV/genética , Integrase de HIV/metabolismo , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológicoRESUMO
BACKGROUND: A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection lasts longer in immunocompromised hosts than in immunocompetent patients. Prolonged infection is associated with a higher probability of selection for novel SARS-CoV-2 mutations, particularly in the spike protein, a critical target for vaccines and therapeutics. METHODS: From December 2020 to September 2022, respiratory samples from 444 immunocompromised patients and 234 health care workers positive for SARS-CoV-2, diagnosed at 2 hospitals in Paris, France, were analyzed using whole-genome sequencing using Nanopore technology. Custom scripts were developed to assess the SARS-CoV-2 genetic diversity between the 2 groups and within the host. RESULTS: Most infections were SARS-CoV-2 Delta or Omicron lineages. Viral genetic diversity was significantly higher in infections of immunocompromised patients than those of controls. Minor mutations were identified in viruses sequenced from immunocompromised individuals, which became signature mutations for newer SARS-CoV-2 variants as the epidemic progressed. Two patients were coinfected with Delta and Omicron variants. The follow-up of immunocompromised patients revealed that the SARS-CoV-2 genome evolution differed in the upper and lower respiratory tracts. CONCLUSIONS: This study found that SARS-CoV-2 infection in immunocompromised patients is associated with higher genetic diversity, which could lead to the emergence of new SARS-CoV-2 variants with possible immune evasion or different virulence characteristics.
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COVID-19 , SARS-CoV-2 , Humanos , Estudos de Casos e Controles , Estudos Retrospectivos , SARS-CoV-2/genética , Hospedeiro Imunocomprometido , MutaçãoRESUMO
Crimean-Congo hemorrhagic fever virus (CCHFV) is the causative agent of Crimean-Congo hemorrhagic fever (CCHF), a highly contagious and potentially fatal emerging disease. We assessed CCHFV seroprevalence by conducting a serological survey of two cohorts from Brazzaville, Congo and Bamako, Mali. We retrospectively screened 581 sera samples, including 352 from monitoring centers for people living with HIV (PLWH) in Brazzaville and 229 provided by the Blood Transfusion Center at Gabriel Touré Hospital in Bamako. An ELISA kit (ID Screen® CCHF Double Antigen Multi-species, Innovative Diagnostics) was used to detect total anti-CCHFV antibodies in serum. CCHFV seroprevalence was 0.6% in the PLWH cohort in Brazzaville, all in a periurban area near livestock/agriculture, and 1.75% in a cohort of blood donors in Bamako, half living in a periurban area near livestock/agriculture and the others performing risk-exposure activities, such as working as a butcher or with frequent rural travels. PLWH from Brazzaville were mostly female, older, and more highly educated, with a tertiary sector activity and living in an urban biotope without livestock/agricultural activities in the surroundings, in contrast to the blood donors of Bamako, who were younger and more likely to live in periurban/rural areas with livestock/agricultural activities in the surroundings. Despite a low CCHFV seroprevalence, our study indicates human contact with CCHFV in sub-urban areas of the capital cities of Congo and Mali associated with previously described CCHFV risk factors.
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Infecções por HIV , Vírus da Febre Hemorrágica da Crimeia-Congo , Febre Hemorrágica da Crimeia , Animais , Humanos , Feminino , Masculino , Estudos Soroepidemiológicos , Mali/epidemiologia , Doadores de Sangue , Estudos Retrospectivos , Anticorpos Antivirais , Gado , Infecções por HIV/epidemiologiaRESUMO
BACKGROUND: High-risk patients, often immunocompromised and not responding to vaccine, continue to experience severe COVID-19 and death. Monoclonal antibodies (mAbs) were shown effective to prevent severe COVID-19 for these patients. Nevertheless, concerns about the emergence of resistance mutations were raised. METHODS: We conducted a multicentric prospective cohort study, including 264 patients with mild-to moderate COVID-19 at high risk for progression to severe COVID-19 and treated early with Casirivimab/Imdevimab, Sotrovimab or Tixagevimab/Cilgavimab. We sequenced the SARS-CoV-2 genome during follow-up and searched for emerging Spike mutations. RESULTS: Immunocompromised patients have a 6-fold increased risk of developing mutations, which are associated with a prolonged duration of viral clearance but no clinical worsening. Emerging P337S/R/L/H, E340D/K/A/Q/V/G and K356T/R substitutions in patients treated with Sotrovimab are associated with higher viral RNA loads for up to 14 days post-treatment initiation. Tixagevimab/Cilgavimab is associated with a 5-fold increased risk of developing mutations. R346K/I/T/S and K444R/N/M substitutions associated with Tixagevimab/Cilgavimab have been identified in multiple SARS-CoV-2 lineages, including BQ.1 and XBB. CONCLUSIONS: In conclusion, the probability of emerging mutations arising in response to mAbs is significant, emphasizing the crucial need to investigate these mutations thoroughly and assess their impact on patients and the evolutionary trajectory of the SARS-CoV-2.
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Background: To investigate the impact of the M184V/I mutation on virologic response to dolutegravir plus lamivudine (DTG + 3TC) in suppressed-switch populations, a meta-analysis was performed using virologic outcomes from people with human immunodeficiency virus type 1 (PWH) with and without M184V/I before DTG + 3TC switch in real-world studies identified via systematic literature review. Sensitivity analyses were performed using data from PWH with M184V/I in interventional studies identified via targeted literature review. Methods: Single-arm meta-analyses using common- and random-effects models were used to estimate proportions of PWH with virologic failure (VF) among real-world populations with and without M184V/I and interventional study participants with M184V/I at 24, 48, and 96 weeks. Results: Literature reviews identified 5 real-world studies from 3907 publications and 51 abstracts meeting inclusion criteria and 5 interventional studies from 1789 publications and 3 abstracts. All time points had low VF incidence in PWH with M184V/I (real-world: 1.43%-3.81%; interventional: 0.00%) and without (real-world: 0.73%-2.37%). Meta-analysis-estimated proportions (95% confidence interval) with VF were low at weeks 24, 48, and 96, respectively, for PWH with M184V/I (real-world: 0.01 [.00-.04], 0.03 [.01-.06], and 0.04 [.01-.07]; interventional: 0.00 [.00-.02], 0.00 [.00-.01], and 0.00 [.00-.03]) and without (real-world: 0.00 [.00-.02], 0.02 [.01-.04], and 0.02 [.00-.05]). One real-world study (n = 712) reported treatment-emergent M184V at VF in 1 of 652 (0.15%) PWH without prior M184V/I. Conclusions: Results suggest that prior M184V/I has minimal impact on virologic suppression after switching to DTG + 3TC and provide reassurance when considering switching regimens in virologically suppressed PWH with incomplete treatment history or limited treatment options.
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We compared 2 human papillomavirus (HPV) assays to detect the 14 high-risk HPV (hrHPV) genotypes in self-collected anal samples. We found a good agreement and similar performance to detect HPV-16, HPV-18, and the 12 other hrHPV genotypes. The global performance to detect the 14 hrHPV genotypes was not significantly different between the 2 assays.
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Antibodies effective against the recent Omicron sublineages are missing. By taking advantage of a multi-centric prospective cohort of immunocompromised individuals treated for mild-to-moderate COVID-19, Bruel et al. show that administration of 500 mg of sotrovimab induces serum neutralization and antibody-dependent cellular cytotoxicity of BQ.1.1 and XBB.1.5. Therefore, sotrovimab may remain a therapeutic option against these variants.
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Anticorpos Monoclonais Humanizados , Hospedeiro Imunocomprometido , Humanos , Estudos Prospectivos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêuticoRESUMO
BACKGROUND: Mortality is high in older patients hospitalized with COVID-19. Previous studies observed lower mortality during the Omicron wave, yet no data is available on older patients. The objective was to compare in-hospital mortality between the Omicron and previous waves in older patients hospitalized with COVID-19. METHODS: This retrospective observational multicenter cohort study used the Greater Paris University Hospitals Group's data warehouse (38 hospitals). Patients aged ≥ 75 years with a confirmed COVID-19 diagnosis and hospitalized from March 2020 to January 2022 were included. The study period was divided into five waves. The fifth wave (January 1st to 31st 2022) was considered as the Omicron wave as it was the predominant variant (≥ 50%), and was compared with waves 1 (March-July 2020), 2 (August-December 2020), 3 (January-June 2021) and 4 (July-December 2021). Primary outcome was in-hospital mortality. Secondary outcome was occurrence of ICU admission or in-hospital death. Multivariate logistic regression was performed, with a sensitivity analysis according to variant type. RESULTS: Of the 195,084 patients hospitalized with COVID-19, 19,909 patients aged ≥ 75 years were included (median age 85 [IQR 79-90] years, 53% women). Overall in-hospital mortality was 4,337 (22%), reaching 345 (17%) during wave 5. Waves 1 and 3 were significantly associated with increased in-hospital mortality in comparison with wave 5 (adjusted Odds Ratios aOR 1.42 [95%CI 1.21-1.66] and 1.56 [95%CI 1.33-1.83] respectively). Waves 1 to 3 were associated with an increased risk of occurrence of ICU admission or in-hospital death in comparison with wave 5: aOR 1.29 [95% CI 1.12 to 1.49] for wave 1, aOR 1.25 [95% CI 1.08 to 1.45] for wave 2 and aOR 1.56 [95% CI 1.36 to 1.79] for wave 3. Sensitivity analysis found that Omicron variant was associated with decreased mortality, in comparison with previous variants. CONCLUSIONS: Mortality was lower during the 5th Omicron wave in the older population, but remained high, implying that this variant could be considered as "milder" but not "mild". This persistently high mortality during the 5th Omicron wave highlights the importance of including older patients in clinical trials to confirm the benefit/risk balance of COVID-19 treatments in this fragile population.
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Teste para COVID-19 , COVID-19 , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Mortalidade Hospitalar , Estudos de Coortes , Paris/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Hospitais UniversitáriosRESUMO
⢠Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. ⢠HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. ⢠Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. ⢠Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. ⢠In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. ⢠Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Filogenia , HIV-1/genética , Farmacorresistência Viral/genética , Antirretrovirais/uso terapêutico , Mutação , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêuticoRESUMO
Background: Monoclonal antibodies (mAbs) targeting the spike of SARS-CoV-2 prevent severe COVID-19. Omicron subvariants BQ.1.1 and XBB.1.5 evade neutralization of therapeutic mAbs, leading to recommendations against their use. Yet, the antiviral activities of mAbs in treated patients remain ill-defined. Methods: We investigated neutralization and antibody-dependent cellular cytotoxicity (ADCC) of D614G, BQ.1.1 and XBB.1.5 in 320 sera from 80 immunocompromised patients with mild-to-moderate COVID-19 prospectively treated with mAbs (sotrovimab, n=29; imdevimab/casirivimab, n=34; cilgavimab/tixagevimab, n=4) or anti-protease (nirmatrelvir/ritonavir, n=13). We measured live-virus neutralization titers and quantified ADCC with a reporter assay. Findings: Only Sotrovimab elicits serum neutralization and ADCC against BQ.1.1 and XBB.1.5. As compared to D614G, sotrovimab neutralization titers of BQ.1.1 and XBB.1.5 are reduced (71- and 58-fold, respectively), but ADCC levels are only slightly decreased (1.4- and 1-fold, for BQ.1.1 and XBB.1.5, respectively). Interpretation: Our results show that sotrovimab is active against BQ.1.1 and XBB.1.5 in treated individuals, suggesting that it may be a valuable therapeutic option.