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BACKGROUND: Severe and prolonged mpox courses have been described during the 2022-2023 outbreak. Identifying predictors of severe evolution is crucial for improving management and therapeutic strategies. We explored the predictors of mpox severity and tested the association between mpox severity and viral load in biological fluids. We also analysed the predictors of disease duration and kinetics of inflammatory markers and described the viral presence and duration of shedding in biological fluids. METHODS: This multicentre historical cohort study included adults diagnosed with laboratory-confirmed mpox diagnosis between May 2022 and September 2023 at 15 Italian centres. Patients were followed up from the day of diagnosis until clinical recovery. Biological fluids (blood, urine, saliva, and oropharyngeal and rectal swabs) were collected from each subgroup during the course of the disease and after healing. The primary outcomes were disease severity (presence of mucosal involvement, extended rash, or need for hospitalisation) and its association with the cycle threshold value (Ct-value, surrogate of viral load) in biological fluids, using standard linear and linear mixed-effect logistic regression models. Among the secondary outcomes, predictors of disease duration were assessed using a linear regression model. FINDINGS: A total of 541 patients were enrolled, including four (0.74%) women, with a median age of 38 years (IQR 33-44). Among the 235 people living with HIV (PLWH) (43.44%), 22 (4.07%) had a CD4 count lower than 350 cells/µL. Severe mpox was reported in 215 patients (39.74%). No patient died. Multivariable analysis showed that, severe mpox was more likely among Caucasians (OR 1.82; 95% CI 1.14-2.90, p = 0.012) and patients who had an onset of fever (1.95; 1.27-2.99, p = 0.002), lymphadenopathy (2.30; 1.52-3.48, p < 0.001), sore throat (2.14; 1.27-3.59, p = 0.004), and peri-anal lesions (2.91; 1.93-4.37, p < 0.001). There was a significant difference (p = 0.003) between the median Ct-value in the upper respiratory tract for patients presenting with either mild (35.15; IQR 28.77-42.01) or severe infection (31.00; 25.00-42.01). The risk of developing severe disease decreased by approximately 5% per Ct increase (0.95; 0.91-0.98; p = 0.005). The disease lasted longer in the case of proctitis (+4.78 days; 1.95-7.61, p = 0.001), sore throat (+3.12; 0.05-6.20, p = 0.046), extended rash (+3.42; 0.55-6.28, p = 0.020), as well as in PLWH with a low CD4 count (+12.51; 6.79-18.22, p < 0.001). INTERPRETATION: The identification of predictors of severe or prolonged disease and the direct association MPXV Ct-value in the upper respiratory tract and disease severity could be useful in establishing proper management and early treatment of new mpox cases. FUNDING: ICONA Foundation; Italian Ministry of Health "Ricerca Corrente Linea 2", INMI Lazzaro Spallanzani IRCCS.
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Objectives: Ixodes ricinus is under-recognized in Europe. This study aimed to determine the seroprevalence and spatial distribution of tick-borne encephalitis (TBE) virus (TBEV) in areas close to endemic regions in Northern Italy. Methods: A multicenter study was conducted on a random sample of the general population afferent to hospitals in Veneto, Lombardy, and Piedmont with a pre-determined sample size of 1500 participants. The presence of TBEV-neutralizing antibodies was determined for sera positive to the TBE-specific immunoglobulin G test in a centralized laboratory. Results: Out of 1537 samples analyzed (790 from Lombardy, 394 from Veneto, 353 from Piedmont), 39 (2.5%) were immunoglobulin G TBEV-positive. The frequency of positive cases was similar amid the regions (24-3.0% Lombardy, 10-2.5% Veneto, and 5-1.4% Piedmont; P = 0.27). The seropositivity rates were 3.6% in subjects aged over 50 years, 2.0% in those aged 30-50 years, and 1.5% in subjects aged under 30 years (P = 0.10). Two of them (one from Veneto and one from Lombardy) were confirmed by TBEV neutralization test (prevalence 130 per 100,000). One lived close to an endemic area (Treviso); the other spent time in an endemic region (Friuli) and did not remember experiencing tick bites. Conclusions: The results from this study highlight the need for raising awareness among the population and health care workers to limit the risk of TBE infection.
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It is debated whether central nervous system involvement begins during acute HIV infection in persons without meningitis/encephalitis and if specific antiretroviral drugs or combinations would be beneficial. Neurologically asymptomatic participants enrolled in a randomized and controlled study comparing three combination antiretroviral regimens (tenofovir alafenamide/emtricitabine plus dolutegravir, darunavir or both) during primary HIV infection were enrolled. Serum and cerebrospinal fluid (CSF) were collected at baseline, 12 and 48 (serum only) weeks after treatment initiation. Single Molecule Array was used to measure neurofilament light chain (NFL), total tau protein (Tau), Brain-Derived Neurotrophic Factor (BDNF), Glial Fibrillary Acidic Protein (GFAP), Ubiquitin C-terminal Hydrolase (UCH-L1). We assessed the longitudinal change in biomarkers over time as well as the change in the prevalence of serum NFL concentrations above previously published age-adjusted cut-offs (7â pg/mL if 5-18 years, 10â pg/mL if 18-51 years, 15â pg/mL if 51-61 years, 20â pg/mL if 61-70 years and 35â pg/mL if >70 years). Serum was available from 47 participants at all time points while CSF was in 13 and 7 participants (baseline/W12). We observed a significant direct serum-to-CSF correlation for NFL (rho = 0.692, p = 0.009), GFAP (rho = 0.659, p = 0.014) and BDNF (rho = 0.587, p = 0.045). Serum (rho = 0.560, p = 0.046) and CSF NFL (rho = 0.582, p = 0.037) concentrations were directly associated with CSF HIV RNA levels. We observed a significant decrease over time in serum NFL (p = 0.006) and GFAP (p = 0.006) but not in the other biomarkers. No significant difference was observed among the treatment arms. At baseline, serum and CSF age-adjusted NFL levels were above age-adjusted cut-offs in 23 (48.9%) and 4 participants (30.8%); considering serum NFL, this proportion was lower at weeks 12 (31.9%, p = 0.057) and 48 (27.7%, p = 0.13). A relevant proportion of neurologically asymptomatic participants had abnormal CSF and serum NFL levels during primary HIV infection. NFL and GFAP decreased in serum following combination antiretroviral therapy without significant differences among the treatment arms.
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ABSTRACT: This is a retrospective study on MSM diagnosed with rectal LGV, treated with 7 or 21 days of doxycycline between 2015-2022. Overall, 143 MSM were included: 58 (41%) had LGV. 100% microbiologic cure was found among MSM with symptomatic or asymptomatic LGV treated with 7 and 21 days of doxycycline.
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Background: The aim of the study was to evaluate the 12-month cumulative probability of treatment discontinuation (TD) in people with human immunodeficiency virus (HIV; PWH) and a long exposure to antiretroviral therapy (ART) switching to long-acting cabotegravir and rilpivirine (CAB/RPV). Methods: SCohoLART is a single-center, prospective, cohort study designed to collect both samples and clinical data from PWH with virological suppression who switched to bimonthly long-acting CAB/RPV. TD occurred at switch to another regimen for any reason including virological failure (VF); VF was defined as HIV RNA levels ≥50 copies/mL at 2 consecutive measurements or a single HIV RNA level ≥1000 copies/mL. Results were reported as median (interquartile range [IQR]) or frequency (percentage). Cumulative probabilities of TD were estimated using Kaplan-Meier curves. Results: We evaluated 514 participants; 467 (90.9%) were male, and their median age (IQR) was 49 (40-56) years. At the time of switching, the median time from HIV diagnosis and the median duration of ART were 14.0 (IQR, 8.8-20.5) and 11.4 (7.9-17.4) years, respectively; before starting CAB/RPV, the median number of antiretroviral regimens was 3 (2-4). During a median study follow-up (IQR) of 13.1 (9.1-15.5) months, 52 PWH (10.1%) experienced TD, including 4 (0.8%) for VF. The 12-month cumulative probability of TD was 11% (95% confidence interval, 8%-14%). The main cause of TD was injection site reaction (15 participants [28.8%]). Conclusions: The 1-year cumulative probability of TD with long-acting CAB/RPV was quite low in this cohort of people with a median exposure to ART of 10 years, in whom injection site reaction was the leading cause of TD. VFs were rare during study follow-up.
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Despite its effectiveness, combination antiretroviral treatment (cART) has a limited effect on HIV DNA reservoir, which establishes early during primary HIV infection (PHI) and is maintained by latency, homeostatic T-cells proliferation, and residual replication. This limited effect can be associated with low drug exposure in lymphoid tissues and/or suboptimal adherence to antiretroviral drugs (ARVs). The aim of this study was to assess ARV concentrations in plasma, peripheral blood mononuclear cells (PBMCs) and lymph nodes (LNs), and their association to HIV RNA and HIV DNA decay during PHI. Participants were randomised to receive standard doses of darunavir/cobicistat (Arm I), dolutegravir (Arm II) or both (Arm III), with a backbone of tenofovir alafenamide and emtricitabine. Total HIV DNA was measured using digital-droplet PCR in PBMCs at baseline, 12 and 48 weeks. Drug concentrations in plasma and PBMCs were determined at 2, 12 and 48 weeks (LNs at 12 weeks) by UHPLC-MS/MS. Seventy-two participants were enrolled, mostly male (n=68), with a median age of 34 years and variable Fiebig stages (V-VI 57.7%, I-II 23.9%, and III-IV 18.3%). Twenty-six patients were assigned to Arm I, 27 to Arm II and 19 to Arm III. After 48 weeks, most patients had undetectable viremia, with minor differences in HIV RNA decay between arms. Patients with Fiebig I-II showed faster HIV RNA and HIV DNA decay. Intracellular tissue penetration was high for nucleoside analogues and low-moderate for darunavir and dolutegravir. Only tenofovir diphosphate concentrations in PBMCs showed correlation with HIV DNA decay. Overall, these results indicate that the timing of treatment initiation and intracellular tenofovir penetration are primary and secondary factors, respectively, affecting HIV reservoir.
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DNA Viral , Infecções por HIV , Leucócitos Mononucleares , Linfonodos , Tenofovir , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Masculino , Adulto , Feminino , DNA Viral/sangue , Leucócitos Mononucleares/virologia , Linfonodos/virologia , Tenofovir/uso terapêutico , Tenofovir/farmacocinética , Tenofovir/sangue , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/sangue , Oxazinas , Pessoa de Meia-Idade , RNA Viral/sangue , Plasma/química , Plasma/virologia , Piperazinas/sangue , Emtricitabina/uso terapêutico , Emtricitabina/farmacocinética , Emtricitabina/sangue , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/sangue , Piridonas/uso terapêutico , Darunavir/uso terapêutico , Darunavir/farmacocinética , Darunavir/sangue , HIV-1/efeitos dos fármacos , Carga Viral , Alanina/sangue , Antirretrovirais/uso terapêutico , Antirretrovirais/farmacocinética , Antirretrovirais/sangueRESUMO
A natural monkeypox virus infection may not induce sufficient neutralizing antibody responses in a subset of healthy individuals. The aim of this study was to evaluate monkeypox virus-neutralizing antibodies six months after infection and to assess the virological factors predictive of a poor immunological response. Antibodies were assessed using a plaque reduction neutralization test at six months from mpox infection; mpox cutaneous, oropharyngeal, and anal swabs, semen, and plasma samples were tested during infection. Overall, 95 people were included in the study; all developed detectable antibodies. People who were positive for the monkeypox virus for more days had higher levels of antibodies when considering all tested samples (p = 0.029) and all swabs (p = 0.005). Mpox cycle threshold values were not predictive of antibody titers. This study found that the overall days of monkeypox virus detection in the body, irrespective of the viral loads, were directly correlated with monkeypox virus neutralizing antibodies at six months after infection.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Monkeypox virus , Mpox , Testes de Neutralização , Carga Viral , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Humanos , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Monkeypox virus/imunologia , Masculino , Mpox/imunologia , Mpox/virologia , Adulto , Feminino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVES: To assess the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) among people poorly represented in clinical trials and potentially at higher risk of suboptimal response to ART. METHODS: Observational cohort study on persons with HIV (PWH) enrolled in ICONA who started BIC/FTC/TAF as initial therapy or as switching regimen while virologically suppressed. Primary endpoint was time to treatment failure (TF): new AIDS/death or virological failure (VF) or discontinuation for toxicity/failure. Secondary endpoints were time to treatment discontinuation for toxicity (TDT) and to VF. Groups of interest were those aged >50â years, female sex, and advanced HIV disease at first ART start. Probability of the events overall and according to groups and adjusted HR for every endpoint were calculated by Kaplan-Meier curves and Cox regression models. RESULTS: Nine hundred and thirty-three ART-naive and 1655 ART-experienced PWH initiated BIC/FTC/TAF. Over a median follow-up of 69.8â weeks, 89 (9.6%) PWH at their first regimen experienced TF. PWH aged >50â years had 1.83-fold (95% CI: 1.19-2.83) higher risk of TF; PWH with advanced HIV disease had 2.21-fold (95% CI: 1.53-3.82) higher risk; there were no differences in TF according to sex.Over a median follow-up of 146.3â weeks, 109 (6.6%) out of 1655 switching PWH experienced TF; no differences were found in the risk of TF, TDT and VF according to groups of interest. CONCLUSIONS: Overall, BIC/FTC/TAF is well tolerated and virologically effective in the real-world scenario for ART-naive and -experienced PWH. Older ART-naive PWH and those with advanced HIV disease may respond less well as the burden of diseases might compromise treatment efficacy.
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Fármacos Anti-HIV , Emtricitabina , Infecções por HIV , Compostos Heterocíclicos de 4 ou mais Anéis , Piridonas , Tenofovir , Humanos , Infecções por HIV/tratamento farmacológico , Feminino , Masculino , Pessoa de Meia-Idade , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Emtricitabina/uso terapêutico , Emtricitabina/administração & dosagem , Estudos de Coortes , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Adulto , Piridonas/uso terapêutico , Resultado do Tratamento , Alanina/uso terapêutico , Amidas/uso terapêutico , Piperazinas/uso terapêutico , Piperazinas/administração & dosagem , Adenina/análogos & derivados , Adenina/uso terapêutico , Adenina/administração & dosagem , Adenina/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Carga Viral/efeitos dos fármacos , Combinação de Medicamentos , Substituição de MedicamentosRESUMO
BACKGROUND: Neisseria gonorrhoeae (Ng) is a public health priority because of the rapid evolution of antimicrobial resistance, the emergence of antibiotic resistance, and the absence of a vaccine against Ng. The aim of this study was to investigate trends in the minimum inhibitory concentration and resistance (R) or reduced susceptibility (DS) of Ng cases to ceftriaxone (CRO), azithromycin (AZM), tetracycline (TET), benzylpenicillin (PenG), and ciprofloxacin (CIP) during a 10-year period. METHODS: We conducted a retrospective analysis on an open cohort of Ng cases diagnosed on rectal, urethral, and pharyngeal samples at San Raffaele Scientific Institute, between September 2012 and February 2023. Minimum inhibitory concentrations of antibiotics were determined by gradient-test strips. Bivariate linear regression models were applied on logarithmic minimum inhibitory concentrations values; Cochran-Armitage test was used to determine a linear trend in the proportions of resistant strains. RESULTS: A total of 436 Ng isolates from 352 individuals were analyzed. Minimum inhibitory concentrations of CRO and PenG reduced over time ( P < 0.001, P = 0.030), AZM increased ( P = 0.001), and CIP and TET did not change ( P = 0.473, P = 0.272). The percentages of resistant strains were as follows: PenG, 89.9%; TET, 90.8%; CIP, 48.2%; AZM, and 4.4%. CRO-DS strains were 8.7%, and only 1 case of CRO-R was identified. The proportion of resistant strains increased over time for AZM ( P = 0.007), TET ( P = 0.001), and CIP ( P < 0.001), whereas it decreased for PenG ( P < 0.001) and CRO-DS/R strains ( P < 0.001). CONCLUSIONS: Ng strains showed high susceptibility to CRO, although we identified cases of DS/R and observed high levels of susceptibility to AZM. Overall, the recommended primary regimen for Ng treatment was confirmed to be effective.
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Antibacterianos , Azitromicina , Gonorreia , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae , Tetraciclina , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/isolamento & purificação , Humanos , Gonorreia/epidemiologia , Gonorreia/microbiologia , Gonorreia/tratamento farmacológico , Estudos Retrospectivos , Antibacterianos/farmacologia , Masculino , Adulto , Feminino , Azitromicina/farmacologia , Itália/epidemiologia , Tetraciclina/farmacologia , Farmacorresistência Bacteriana , Ciprofloxacina/farmacologia , Ceftriaxona/farmacologia , Uretra/microbiologia , Pessoa de Meia-Idade , Adulto Jovem , Penicilina G/farmacologia , Faringe/microbiologia , Reto/microbiologiaRESUMO
Monkeypox virus (MPXV) infection confirmation needs reliable polymerase chain reaction (PCR) assays; in addition, viral clade attribution is a key factor in containment measures, considering a more severe syndrome in clade I and the possibility of simultaneous circulation. This study evaluates the performance of all-in-one STANDARD M10 MPX/OPX (SD BIOSENSOR, South Korea - M10). Frozen samples from 205 subjects were selected and stratified according to routine test results (RealStar® Orthopoxvirus PCR Kit 1.0, Altona DIAGNOTICS, Germany - RS; RS-1): in detail, 100 negative skin lesions (SL) and 200 positive samples at the variable stage of infection were analysed. Positive samples were retested with RS (RS-2). Positive and Negative Percent Agreements (PPA, NPA) were calculated. The median (IQR) Ct values of RS and M10 (OPXV target) assays were highly similar. The PPA of M10 compared to RS-1 was 89.5% considering system interpretation, and 96.0% when the operator classified results as positive if any target was detected; NPA was 100%. Comparing the RS-2 run and M10, an overall concordance of 95.3% between assays was found; however, considering operator interpretation, M10 returned more positive results than RS-2. The occurrence of False-Negative results was likely associated with the influence of thawing on low viral concentration; no False-Positive tests were observed. All samples collected at the time of Mpox diagnosis were positive and M10 correctly attributed the clade (West-Africa/II). The M10 MPX/OPX assay demonstrated high reliability in confirming MPXV infection and clade attribution.
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Monkeypox virus , Mpox , Humanos , Monkeypox virus/genética , Mpox/diagnóstico , Reprodutibilidade dos Testes , DNA Viral/genética , África OcidentalRESUMO
BACKGROUND: Mpox virus (MPXV) has recently spread outside of sub-Saharan Africa. This large multicentre study was conducted in Lombardy, the most densely populated Italian region accounting for more than 40% of Italian cases. The present study aims to: i) evaluate the presence and the shedding duration of MPXV DNA in different body compartments correlating the MPXV viability with the time to onset of symptoms; ii) provide evidence of MPXV persistence in different body compartment as a source of infection and iii) characterize the MPXV evolution by whole genome sequencing (WGS) during the outbreak occurred in Italy. MATERIAL AND METHODS: The study included 353 patients with a laboratory-confirmed diagnosis of MPXV infection screened in several clinical specimens in the period May 24th - September 1st, 2022. Viral isolation was attempted from different biological matrices and complete genome sequencing was performed for 61 MPXV strains. RESULTS: MPXV DNA detection was more frequent in the skin (94.4%) with the longest median time of viral clearance (16 days). The actively-replicating virus in cell culture was obtained for 123/377 (32.6%) samples with a significant higher viral quantity on isolation positive samples (20 vs 31, p < 0.001). The phylogenetic analysis highlighted the high genetic identity of the MPXV strains collected, both globally and within the Lombardy region. CONCLUSION: Skin lesion is gold standard material and the high viral load and the actively-replicating virus observed in genital sites confirms that sexual contact plays a key role in the viral transmission.
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DNA Viral , Surtos de Doenças , Eliminação de Partículas Virais , Humanos , Itália/epidemiologia , DNA Viral/genética , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Filogenia , Adulto Jovem , Infecções por Picornaviridae/epidemiologia , Infecções por Picornaviridae/virologia , Adolescente , Sequenciamento Completo do Genoma , Idoso , CriançaRESUMO
Undiagnosed HIV infection is a prominent clinical issue throughout Europe that requires the continuous attention of all healthcare professionals and policymakers to prevent missed testing opportunities and late diagnosis. This systematic review aimed to evaluate interventions to increase HIV testing rates and case detection in European hospitals. Out of 4598 articles identified, 29 studies fulfilled the selection criteria. Most of the studies were conducted in single Western European capital cities, and only one study was from Eastern Europe. The main interventions investigated were test-all and indicator-condition-based testing strategies. Overall, the prevalence of undiagnosed HIV was well above 0.1%. The studied interventions increased the HIV testing rate and the case detection rate. The highest prevalence of undiagnosed HIV was found with the indicator-condition-driven testing strategy, whereas the test-all strategy had the most profound impact on the proportion of late diagnoses. Nevertheless, the HIV testing rates and case-finding varied considerably across studies. In conclusion, effective strategies to promote HIV testing in European hospitals are available, but relevant knowledge gaps regarding generalizability and sustainability remain. These gaps require the promotion of adherence to HIV testing guidelines, as well as additional larger studies representing all European regions.
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The 2022 outbreak of the human mpox virus, formerly known as monkeypox, raised global health concerns with widespread transmission across multiple countries. Sexual transmission emerged as a significant mode of spread, particularly among high-risk groups like MSM and PLWH. This manuscript focuses on the implications of seminal fluids in the transmission of mpox. The virus has been detected in various bodily fluids, including semen, indicating the potential for sexual transmission. Studies have reported high positivity rates of mpox DNA in seminal fluids. Despite some concern about possible contamination due to genital lesions, the presence of replication-competent virus in seminal fluids has been confirmed and mpox virus was also detected in this specimen among people who engaged only in receptive sexual intercourse. Antiviral treatment with tecovirimat showed efficacy in reducing viral presence in semen with detection of the antiviral in this specimen. Virus clearance from semen is relatively rapid and parallels healing from infection, with no reported cases of seminal fluid relapses. The WHO recommendation to avoid condomless intercourse for 12 weeks after clinical healing still appears prudent. Continued research and surveillance are essential to understand viral dynamics and develop effective prevention measures to combat the spread of mpox through sexual transmission and protect key-populations.
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Monkeypox virus , Mpox , Humanos , Sêmen , Fezes , AntiviraisRESUMO
BACKGROUND: Since May, 2022, a large global outbreak of human mpox (formerly known as monkeypox) has predominantly affected men who have sex with men. The strain responsible, Clade IIb, has mutated substantially from precursors originating from the 2017-18 outbreak in Nigeria. Immunity to smallpox, another orthopoxvirus, via previous infection or vaccination provides lifelong immunity. However, since the 2022 mpox outbreak, recent clusters were described in individuals with presumed immunity through recent infection or vaccination. We aim to describe the epidemiological and clinical characteristics of mpox in individuals with past infection or vaccination to improve the understanding of this disease in the setting of previous immunity. METHODS: In this global case series, international collaborators from nine countries provided data on individuals with PCR-confirmed mpox after documented previous infection or vaccination between May 11, 2022, and June 30, 2023. We excluded cases that could not confirm vaccination status or cases with partial immunisation or any doses received before the current multi-national mpox outbreak (cutoff date May 1, 2022). Data were collected via a case report spreadsheet that reported on dates of infection and vaccination, route of immunisation, demographic characteristics, clinical findings, HIV status, concomitant sexually transmitted infections, and markers of disease severity (mpox severity score system). We describe case epidemiology, clinical course, and mpox severity scores; all analyses were descriptive. FINDINGS: We report mpox infections in 37 gay and bisexual men who have sex with men: seven individuals had mpox reinfections, 29 individuals had mpox infections that occurred after two appropriately spaced Modified Vaccinia Ankara-Bavarian Nordic vaccine courses, and one individual had an infection that met the criteria for both reinfection and infection after vaccination. The median age of individuals was 36 years (IQR 30-45; range 21-58). Those with natural immunity after initial infection had a shorter disease course with less mucosal disease upon reinfection than with their initial infection. Infections post-vaccination were characterised by few lesions, little mucosal disease, and minimal analgesia requirements; two people received oral tecovirimat. Overall, there were no deaths, no bacterial superinfections, and all individuals were managed in the ambulatory clinic with one hospital admission for a necrotising neck lesion. INTERPRETATION: The epidemiology of people with mpox reinfection or infection post-vaccination was similar to other published cohorts during the 2022 outbreak-predominantly young, sexually active gay and bisexual men who have sex with men. Clinical features and outcomes of repeat infection and infection after vaccination appear to be less clinically severe than those described in 2022 case literature. Specifically, compared with the 2022 case series, these individuals in the present study had fewer confluent lesions, less mucosal involvement, reduced analgesia requirement, and fewer admissions. Natural immunity and vaccine-induced immunity are not fully protective against mpox infection. However, in this small series both disease duration and severity appear to be reduced. FUNDING: None.
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Mpox , Minorias Sexuais e de Gênero , Vacinas , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Homossexualidade Masculina , Reinfecção , VacinaçãoRESUMO
Aim was to investigate the propensity to switch to long-acting injectable HIV pre-exposure prophylaxis (PrEP) with cabotegravir among oral PrEP-experienced men who have sex with men. Out of 377 PrEP users, 325 (86.2%) were interested (would like = 210) or considering (would consider = 115) switch to long-acting PrEP. At multivariable analysis, the odds ratio of interest in long-acting PrEP in non-adherent vs. adherent individuals to oral PrEP was 5.03 (95%CI = 1.73-14.61,p = 0.003) and of consideration 1.63 (95%CI = 0.51-5.23,p = 0.410). We observed very high propensity to switch to long-acting PrEP, particularly among non-adherent users. Rapid availability of long-acting PrEP might address unmet needs of PrEP users in Italy.
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Fármacos Anti-HIV , Dicetopiperazinas , Infecções por HIV , Profilaxia Pré-Exposição , Piridonas , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Itália/epidemiologiaRESUMO
INTRODUCTION: Impairment of the gastrointestinal barrier leads to microbial translocation and peripheral immune activation, which are linked to disease progression. Data in the setting of primary HIV/SIV infection suggest that gut barrier damage is one of the first events of the pathogenic cascade, preceding mucosal immune dysfunction and microbial translocation. We assessed gut structure and immunity as well as microbial translocation in acutely and chronically-infected, combination antiretroviral therapy (cART)-naive individuals. METHODS: Fifteen people with primary HIV infection (P-HIV) and 13 with chronic HIV infection (C-HIV) c-ART-naive participants were cross-sectionally studied. Gut biopsies were analysed in terms of gut reservoirs (total, integrated and unintegrated HIV DNA); tight junction proteins (E-cadherin, Zonula Occludens-1), CD4 + expression, neutrophil myeloperoxidase (histochemical staining); collagen deposition (Masson staining). Flow cytometry was used to assess γδ T-cell frequency (CD3 + panγδ+Vδ1+/Vδ2+). In plasma, we measured microbial translocation (LPS, sCD14, EndoCAb) and gut barrier function (I-FABP) markers (ELISA). RESULTS: P-HIV displayed significantly higher tissue HIV DNA, yet neutrophil infiltration and collagen deposition in the gut were similar in the two groups. In contrast, microbial translocation markers were significantly lower in P-HIV compared with C-HIV. A trend to higher mucosal E-cadherin, and gut γδ T-cells was also observed in P-HIV. CONCLUSION: Early HIV infection features higher HIV DNA in the gut, yet comparable mucosal alterations to those observed in chronic infection. In contrast, microbial translocation is contained in primary HIV infection, likely because of a partial preservation of E-cadherin and mucosal immune subsets, namely γδ T-cells.