RESUMO
The association between human papillomavirus (HPV) and other sexually transmitted infections (STIs) in anal lesions still remains unclear. Aim of the study was to evaluate the prevalence of simultaneous infection of HPV and Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis in individuals screened for HPV anal infection. A total of 507 anal samples were tested for both anal HPV and STIs: 16% resulted positive for one or more non-HPV STIs. Specifically, C. trachomatis, M. genitalium, and N. gonorrhoeae were detected in 8%, 5%, and 4% of cases, respectively. Two groups were considered, including a positive STI group and a negative STI group. The prevalence of HPV was similar in patients in both groups: high risk (HR)-HPV and low risk (LR)-HPV were 67% and 53% versus 62% (p = 0.361) and 54% (p = 0.864) of patients, respectively. However, HPV 16, 18, 35, 51, 59, and 69 were significantly more frequent in patients tested positive for other STIs versus HPV infection alone (p < 0.05). No significant differences between the two groups were observed in vaccination coverage, 28% versus 32% (p = 0.463), and HIV status, 86% versus 84% (p = 0.658). The study shows that the overall HPV status is not directly correlated to other STIs in the investigated population, except for certain HPV types, including HR-HPV 16, reinforcing the urge for a greater vaccination coverage.
Assuntos
Coinfecção , Infecções por Papillomavirus , Infecções Sexualmente Transmissíveis , Humanos , Feminino , Prevalência , Adulto , Masculino , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Pessoa de Meia-Idade , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/virologia , Adulto Jovem , Coinfecção/epidemiologia , Coinfecção/virologia , Adolescente , Canal Anal/virologia , Canal Anal/microbiologia , Mycoplasma genitalium/isolamento & purificação , Papillomaviridae/isolamento & purificação , Papillomaviridae/genética , Papillomaviridae/classificação , Idoso , Chlamydia trachomatis/isolamento & purificação , Gonorreia/epidemiologia , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/microbiologia , Trichomonas vaginalis/isolamento & purificação , Infecções por Mycoplasma/epidemiologia , Neisseria gonorrhoeae/isolamento & purificaçãoRESUMO
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.
RESUMO
Pre-exposure prophylaxis (PrEP) is a pivotal intervention among HIV prevention strategies. We aimed to narratively revise the topic of HIV acute infection in the setting of PrEP exposure with a focus on diagnostic options, clinical features, and future PrEP perspectives, with a particular focus on users with high adherence to PrEP. We searched the main databases (PubMed, Embase, and Scopus) with the keywords "PrEP" or "Pre-Exposure Prophylaxis" and "HIV" or "PLWH" and "breakthrough" or "acute infection" or "primary infection". We included all randomized clinical trials and non-experimental studies (both case reports and observational studies) ever published. In the present narrative review, we revise the diagnostic challenges related to HIV diagnosis in the setting of PrEP and the clinical characteristics and symptoms of breakthrough infections. We discuss the management of acute HIV infection during PrEP and the new challenges that arise from the use of long-acting drugs for PrEP. Our review underlines that although extremely rare, HIV seroconversions are still possible during PrEP, even in a context of high adherence. Efforts to promptly identify these events must be included in the PrEP follow-up in order to minimize the chance of overlooked HIV breakthrough infections and thus exposure to suboptimal concentrations of antiretrovirals.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adesão à Medicação , Profilaxia Pré-Exposição , Humanos , Infecções por HIV/prevenção & controle , Fármacos Anti-HIV/uso terapêuticoAssuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Itália , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/economia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Pacientes Ambulatoriais , Redução de Custos , Estudos de Coortes , Tenofovir/uso terapêuticoAssuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Humanos , Masculino , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/imunologia , Feminino , VacinaçãoAssuntos
Interações Medicamentosas , Infecções por HIV , Neoplasias , Organofosfatos , Humanos , Infecções por HIV/tratamento farmacológico , Neoplasias/tratamento farmacológico , Organofosfatos/uso terapêutico , Organofosfatos/farmacologia , Fármacos Anti-HIV/uso terapêutico , Masculino , Pessoa de Meia-Idade , Feminino , PiperazinasRESUMO
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.
Assuntos
Monkeypox virus , Mpox , Humanos , Monkeypox virus/genética , Mpox/diagnóstico , Reprodutibilidade dos Testes , DNA Viral/genética , África OcidentalRESUMO
OBJECTIVE: Large inter-individual variability in the pharmacokinetics of rilpivirine and cabotegravir has been reported in the first weeks after starting long-acting injectable (LAI) therapy. Here, we assessed the distribution of rilpivirine and cabotegravir trough concentrations in people with HIV (PWH) on long-term LAI treatment. METHODS: Adult PWH treated with LAI for at least 32 weeks with an assessment of drug plasma trough concentrations were considered. The proportion of rilpivirine and cabotegravir plasma trough concentrations below four-times the protein-adjusted concentrations required for 90% inhibition of viral replication (4×PA-IC90) was estimated. RESULTS: Sixty-seven PWH were identified. LAI treatment duration was 216â±â80 weeks (range 32-320 weeks). Cabotegravir concentrations were associated with lower inter-individual variability compared with rilpivirine (45% versus 84%; Pâ<â0.05). No differences were found in rilpivirine (160â±â118 versus 189â±â81 ng/mL; Pâ=â0.430) and cabotegravir (1758â±â807 versus 1969â±â802 ng/mL; Pâ=â0.416) trough concentrations in males (nâ=â55) versus females (nâ=â12). A non-significant trend for lower cabotegravir concentrations was found in PWH with a body mass index >30 kg/m2 (nâ=â9) versus non-obese participants (1916â±â905 versus 1606â±â576 ng/mL; Pâ=â0.131). Three out of the 67 PWH had at least one drug concentration <4×PA-IC90: 100% of PWH had undetectable HIV viral load. CONCLUSIONS: At steady state, optimal systemic exposure of cabotegravir and rilpivirine was found in most PWH; cabotegravir trough concentrations were associated with lower inter-individual variability compared with rilpivirine. The study was not powered to assess the contribution of sex and/or body weight on LAI exposure due to the small number of females and obese PWH included.
Assuntos
Fármacos Anti-HIV , Dicetopiperazinas , Infecções por HIV , Piridonas , Rilpivirina , Humanos , Rilpivirina/farmacocinética , Rilpivirina/administração & dosagem , Rilpivirina/uso terapêutico , Rilpivirina/sangue , Masculino , Feminino , Infecções por HIV/tratamento farmacológico , Pessoa de Meia-Idade , Adulto , Piridonas/farmacocinética , Piridonas/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/uso terapêutico , Idoso , Injeções , Carga Viral/efeitos dos fármacosRESUMO
Italian guidelines recommend HIV pre-exposure prophylaxis (PrEP) only upon satisfying strict eligibility criteria. The objective of this study is to evaluate if PrEP candidates attending a community-based service comply with these criteria and whether these prescribing conditions affect retention in care and sexually transmitted infections (STIs) acquisition. A retrospective analysis was performed on PrEP candidates evaluated from January 2019 to June 2022. Data were collected from self-administered questionnaires and clinical files. The population was divided in subjects with 0/1 (0/1 C) and ≥ 2 (≥ 2 C) criteria. Descriptive statistics and non-parametric tests were employed to describe study population. Incidence of PrEP discontinuation and of STIs was estimated per 100 persons-year of follow up (PYFU), and incidence rate ratio (IRR) was calculated. Univariate and multivariable Cox regression analyses were used to evaluate the association strength between PrEP drop out and other variables. The analyses enrolled 659 individuals: 422 individuals were included in 0/1 C, 237 in ≥ 2 C group, respectively. Inconsistent condom use was the most reported prescribing criteria (399 individuals, 60.6%), followed by a previous STI (186 individuals, 28.2%). 0/1 C exhibited lower STIs incidence. PrEP discontinuation was 29% in 0/1 C and 38% in ≥ 2 C (p = 0.031). Cox model revealed that inconsistent condom use was the only prescribing criteria associated to PrEP persistence. The majority of PrEP candidate did not comply with prescribing conditions. Eligibility criteria failed to identify individuals with better retention in care. Our results suggest that Italian guidelines should be updated removing barriers to prescription.
Assuntos
Infecções por HIV , Profilaxia Pré-Exposição , Retenção nos Cuidados , Infecções Sexualmente Transmissíveis , Humanos , Masculino , Estudos Retrospectivos , Profilaxia Pré-Exposição/estatística & dados numéricos , Adulto , Feminino , Infecções Sexualmente Transmissíveis/prevenção & controle , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/epidemiologia , Infecções por HIV/tratamento farmacológico , Itália/epidemiologia , Retenção nos Cuidados/estatística & dados numéricos , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Incidência , Pessoa de Meia-Idade , Definição da Elegibilidade , Inquéritos e QuestionáriosRESUMO
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.
Assuntos
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 , CriançaAssuntos
Fármacos Anti-HIV , Dicetopiperazinas , Infecções por HIV , Piridonas , Rilpivirina , Humanos , Rilpivirina/uso terapêutico , Rilpivirina/farmacocinética , Rilpivirina/administração & dosagem , Injeções Intramusculares , Infecções por HIV/tratamento farmacológico , Piridonas/farmacocinética , Piridonas/administração & dosagem , Piridonas/uso terapêutico , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , AdultoRESUMO
Human papillomavirus (HPV) is the most common sexually transmitted infection, linked to several types of lesions. HPV, specifically HPV 16, accounts for most of anal cancer cases. In this study, we evaluated the proportion of samples tested positive for HPV and characterized genotypes distribution in anal specimens collected from individuals at risk of anal HPV infection attending from 2018 to 2022 a large Infectious Diseases Department in Italy. The presence of HPV DNA was investigated through a commercial kit detecting 12 HR-HPV, 8 probable/possible HR-HPV, and 8 LR-HPV genotypes. Among 1514 samples, 84% (1266/1514) resulted positive for any type of HPV. The prevalence of high-risk HPV types remained high during all the years of the study period, from 2018 to 2022, ranging from 65% to 73%. Most of HR-HPV, LR-HPV and HPV 16 positive samples were collected from men >45 years. HPV 16 was also the most frequent type in men and women. We did not observe significant variations between years in detection of HR-HPV, instead of LR-HPV, that significantly decreased. In conclusion, the high prevalence of oncogenic HPV genotypes underlines the necessity of clear anal HPV screening guidelines and, along with frequent HR-HPV coinfections, reinforces the urge to intensify the anti-HPV vaccination campaign.
Assuntos
Infecções por Papillomavirus , Masculino , Humanos , Feminino , Prevalência , Infecções por Papillomavirus/epidemiologia , Papillomavirus Humano 16 , Itália/epidemiologia , GenótipoRESUMO
BACKGROUND: Oral human papillomavirus (HPV) is common among healthy individuals but causes and implications of persistent infections are under evaluation in the pathogenesis of head and neck neoplasms. METHODS: This was a retrospective study evaluating the prevalence of high-risk (HR), probable HR and low-risk (LR) HPV types in patients reporting signs/symptoms of oral and upper respiratory tract lesions. Individuals attending between 2019 and 2022 a University Hospital in Milan, Italy, with risk factors for HPV (unprotected oral sex and/or previous documentation of HPV infection in oral and upper respiratory tract and/or another anatomical site) were included. RESULTS: Fourteen out of 110 (12.7%) individuals tested positive for HPV DNA. The prevalence of HR-HPV and LR-HPV was 3.6% (4/110) and 9.1% (10/110), respectively. No probable/possible HR-HPV was detected. Specifically, 10/110 (9.1%) were diagnosed with 1 LR-HPV genotype, 3/110 (2.7%) were infected with 1 HR-HPV and 1/110 had 3 concomitant HR-HPV types. HPV 16 (2.7%, 3/110) and 6 (4.5%, 5/110) were the most common HR and LR types, respectively. One patient positive for HPV 16, 33 and 35 was diagnosed with cancer at the base of the tongue. Two individuals among those who tested positive for HPV DNA reported previous HPV vaccination. CONCLUSIONS: Our data, in line with observations from previous prevalence studies, support the potential role of HPV in head and neck neoplasms. HPV DNA testing should be performed in patients presenting lesions in oral/respiratory tracts and risk factors for HPV. Improvement in HPV vaccination coverage is warranted.
Assuntos
Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Humanos , Infecções por Papillomavirus/epidemiologia , Papillomavirus Humano , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/complicações , DNA , Genótipo , Papillomaviridae/genética , PrevalênciaRESUMO
Mpox is traditionally considered a zoonotic disease with endemic circulation in Africa, but the 2022-2023 outbreak reached an unprecedented high number of cases in non-endemic countries, so that it was declared a public health emergency of international concern. The reasons for this extensive global spread, characterized by sexual transmission amongst men who have sex with men (MSM), have not been fully clarified. The existence of asymptomatic carriers with viable viral shedding might be an explanation and is under-debated after retrospective studies suggested that infection without symptoms might have a prevalence of 6.5%. We aimed to prospectively assess the presence of mpox infection in asymptomatic high-risk MSM using HIV pre-exposure prophylaxis and living with HIV. We selected individuals with no signs of active infection nor suggestive symptoms in the previous 21 days. Eligible individuals collected oral and anal swabs to undergo point-of-care testing for mpox and completed a 21-days follow-up. Seventy-two individuals were enrolled, and none tested positive for mpox infection nor developed symptoms during follow-up. We selected a high-risk population with a significant history of sexual exposure, but we failed to detect any asymptomatic infection. This observation might have important consequences in terms of contact management and epidemic control.