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BACKGROUND: Immune checkpoint inhibitors (ICIs) have been a major advance in cancer management. However, we still lack prospective real-world data regarding their usage in people with HIV infection (PWH). METHODS: The ANRS CO24 OncoVIHAC study (NCT03354936) is an ongoing prospective observational cohort study in France of PWH with cancer treated with ICI. We assessed the incidence of grade ≥3 immune-related adverse events (irAEs). All grade ≥3 irAEs were reviewed by an event review. RESULTS: Between January 17, 2018, and December 05, 2023, 150 participants were recruited from 33 sites and 140 were included in this analysis. At the data cut-off date of December 05, 2023, the median follow-up was 9.2 months (IQR: 3.9-18.3), with a total of 126.2 person-years.Median age was 59 years (IQR: 54-64) and 111 (79.3%) were men. Median time since HIV diagnosis was 25 years (12-31), the median duration on antiretroviral (ARV) was 19.5 years (7.7-25.4), and the CD4 nadir was 117/µL (51-240). ICI regimens comprised anti-programmed cell death protein-1 (PD-1) for 111 (79.3%) participants, anti-programmed death-ligand 1 for 25 (17.9%), a combination of anti-PD-1 and anti-cytotoxic T-lymphocyte associated protein 4 for 3 (2.1%), and anti-PD-1 along with anti-vascular endothelial growth factor receptor for 1 (0.7%). The most frequent cancers were lung (n=65), head/neck (n=15), melanoma (n=12), liver (n=11) and Hodgkin's lymphoma (n=9).During follow-up, a total of 34 grade ≥3 irAEs occurred in 20 participants, leading to an incidence rate of 26.9 per 100 person-years. The Kaplan-Meier estimates of the proportion of participants with at least one episode of grade ≥3 irAEs were 13.8% at 6 months, 15.0% at 12 months and 18.7% at 18 months. One treatment-related death due to myocarditis was reported (0.7%). Multivariable analysis of cumulative incidence showed that participants with time since HIV diagnosis >17 years (incidence rate ratio (IRR)=4.66, p=0.002), with CD4<200 cells/µL (IRR=4.39, p<0.0001), with positive cytomegalovirus (CMV) serology (IRR=2.76, p=0.034), with history of cancer surgery (IRR=3.44, p=0.001) had a higher risk of incidence of grade ≥3 irAEs. CONCLUSION: This study showed that the incidence of a first episode of grade ≥3 irAE was 15.0% (95% CI: 9.6% to 22.9%) at 1 year and the cumulative incidence of all severe irAE episodes was 26.9 per 100 person-years. Low CD4 count, positive CMV serology, history of cancer surgery and a longer time since HIV diagnosis were associated with the occurrence of severe irAEs.
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Infecções por HIV , Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/imunologia , Masculino , Feminino , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Estudos Prospectivos , Pessoa de Meia-Idade , França/epidemiologiaRESUMO
Background: People with HIV (PWH) are aging. Frailty is an age-related condition predictive of hospitalization and mortality. Here, we assessed the frequency and factors associated with frailty transitions at 1-year follow-up in elderly PWH. Methods: Five hundred eight PWH aged 70 years or older who were on antiretroviral treatment were included in the French multicenter SEPTAVIH study in 2019-2020. Participants were classified as robust, prefrail, or frail according to Fried frailty phenotype at baseline and at 1 year. Logistic regression models were used to evaluate socioeconomic and medical factors associated with transition between frailty states. Models were adjusted for gender, age at baseline, education, and period of HIV diagnosis (before vs after 1996). Results: Seventeen PWH died during the 1-year follow-up. Of the remaining 491 PWH (median age, 73 years), frailty status worsened for 18% of participants and improved for 14% at 1 year. Advanced age, baseline CD4+ T-cell count <350 cells/mm3, and type 2 diabetes were associated with transition from prefrailty to frailty (adjusted odds ratio [aOR], 1.10 per 1-year positive difference; 95% CI, 1.01-1.20; aOR, 3.05; 95% CI, 1.14-8.18; and aOR, 2.63; 95% CI, 1.05-6.57; respectively). Being female was associated with more frequent improvement from prefrailty to robustness (aOR, 2.50; 95% CI, 1.09-5.55). Conclusions: Preventing frailty in elderly PWH is a long-term problem, beginning with the early diagnosis of HIV infection and the management of comorbidities.
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BACKGROUND: This study aimed to compare the humoral responses to mRNA COVID-19 vaccination in people living with HIV (PWH) and HIV-negative individuals. METHODS: We included PWH with an undetectable viral load under ART and HIV-negative participants from the French nationwide ANRS COV-POPART cohort who had received two doses of vaccine as a primary vaccination. We compared humoral response between controls and PWH, stratified by CD4 cell count (<200/mm3 and ≥200/mm3 CD4 cell counts) at 1, 6, and 12 months after primary vaccination. RESULTS: A total of 1776 participants were included in this analysis, 684 PWH (99% were on ART, median CD4 counts 673 cells/mm3) and 1092 controls. At 1 month, after adjustment on age, sex, and BMI, PWH had lower seroneutralization titers than controls, and PWH with <200 CD4 cell/mm3 had lower anti-Spike SARS-CoV-2 IgG antibodies. Same results were found at 6 months. However, in participants who received a booster dose between 6 and 12 months postprimary vaccination, we did not observe differences between PWH and controls at 12 months. CONCLUSION: PWH had high responses to primary mRNA COVID-19 vaccination. In those who received a booster dose after 6 months, the humoral response at 12 months increased to similar levels to controls, even in those with low CD4 counts at baseline.
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Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Infecções por HIV , Imunidade Humoral , Imunização Secundária , SARS-CoV-2 , Humanos , Masculino , Feminino , COVID-19/imunologia , COVID-19/prevenção & controle , Pessoa de Meia-Idade , Infecções por HIV/imunologia , França , Anticorpos Antivirais/sangue , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Vacinação , Carga Viral , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Imunoglobulina G/sangueRESUMO
BACKGROUND: People living with HIV (PLWH) are at risk of frailty, which is predictive for death. As an overactivity of the immune system is thought to fuel frailty, we characterized the immune activation profiles linked to frailty. METHODS: We quantified twenty-seven activation markers in forty-six virological responders (four females and forty-two males; median age, 74 years; median duration of infection, 24 years; median duration of undetectability, 13 years), whose frailty was determined according to the Fried criteria. T cell and NK cell activation was evaluated by flow cytometry, using a panel of cell surface markers. Soluble markers of inflammation, and monocyte activation and endothelial activation were measured by ELISA. The participants' immune activation was profiled by an unsupervised double hierarchical clustering analysis. We used ANOVA p-values to rank immunomarkers most related to Fried score. A Linear Discriminant Analysis (LDA) was performed to link immune activation markers to frailty. RESULTS: 41% of the participants were pre-frail, including 24% with a Fried score of 1, and 17% with a Fried score of 2. ANOVA identified the 14 markers of T cell, monocyte, NK cell, endothelial activation, and inflammation the most linked to Fried 3 classes. The LDA performed with these 14 markers was capable of discriminating volunteers according to their Fried score. Two out of the 5 immune activation profiles revealed by the hierarchical clustering were linked to and predictive of pre-frailty. These two profiles were characterized by a low percentage of CD4 T cells and a high percentage of CD8 T cells, activated CD4 T cells, CD8 T cells, and NK cells, and inflammation. CONCLUSIONS: We identified a particular immune activation profile associated with pre-frailty in PLWH. Profiling participants at risk of developing frailty might help to tailor the screening and prevention of medical complications fueled by loss of robustness. Further studies will indicate whether this frailty signature is specific or not of HIV infection, and whether it also precedes frailty in the general population.
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An estimated 38 million people live with human immunodeficiency virus (HIV) worldwide and are at excess risk for multiple cancer types. Elevated cancer risks in people living with HIV (PLWH) are driven primarily by increased exposure to carcinogens, most notably oncogenic viruses acquired through shared transmission routes, plus acceleration of viral carcinogenesis by HIV-related immunosuppression. In the era of widespread antiretroviral therapy (ART), life expectancy of PLWH has increased, with cancer now a leading cause of co-morbidity and death. Furthermore, the types of cancers occurring among PLWH are shifting over time and vary in their relative burden in different parts of the world. In this context, the International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) convened a meeting in September 2022 of multinational and multidisciplinary experts to focus on cancer in PLWH. This report summarizes the proceedings, including a review of the state of the science of cancer descriptive epidemiology, etiology, molecular tumor characterization, primary and secondary prevention, treatment disparities and survival in PLWH around the world. A consensus of key research priorities and recommendations in these domains is also presented.
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Fármacos Anti-HIV , Infecções por HIV , Neoplasias , Estados Unidos/epidemiologia , Humanos , HIV , National Cancer Institute (U.S.) , Neoplasias/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Fármacos Anti-HIV/uso terapêuticoRESUMO
Background: HIV infection induces a 75% increase in the risk of developing neurocognitive impairment (NCI), which has been linked to immune activation. We therefore looked for immune activation markers correlating with NCI. Method: Sixty-five people aged 55-70 years living with controlled HIV-1 infection were enrolled in the study and their neurocognitive ability was assessed according to the Frascati criteria. Fifty-nine markers of T4 cell, T8 cell, NK cell, and monocyte activation, inflammation and endothelial activation were measured in their peripheral blood. White matter hyperintensities (WMH) were identified by magnetic resonance imaging. Double hierarchical clustering was performed for the activation markers and 240 patients including the 65 whose neurocognitive performance had been evaluated. Results: Thirty-eight percent of volunteers presented NCI. Twenty-four percent of them were asymptomatic and fourteen percent had a mild disorder. Strikingly, activated (HLA-DR+) as well as senescent (CD57+CD28-CD27±) T4 cells and T8 cells were less prevalent in the peripheral blood of participants with NCI than in participants without the disorder. Accordingly, the percentage of HLA-DR+ T4 cells was lower in volunteers with periventricular and deep WMH. The double hierarchical clustering unveiled six different immune activation profiles. The neurocognitive performances of participants with two of these six profiles were poor. Here again, these two profiles were characterized by a low level of T4 and T8 cell activation and senescence. Conclusion: Our observation of low circulating levels of activated and senescent T cells in HIV-1 patients with NCI raises the interesting hypothesis that these lymphocytes may be recruited into the central nervous system.
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Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , Linfócitos T CD4-Positivos , Antígenos HLA-DR , Transtornos Neurocognitivos/complicações , BiomarcadoresRESUMO
OBJECTIVE: Cerebral vasculitis (CV) is a severe complication of pneumococcal meningitis (PM); whether dexamethasone use can reduce its occurrence remains to be determined. METHODS: This is a retrospective observational bicentric study analyzing all adults with proven PM hospitalized between January 2002 and December 2020 in two tertiary hospitals. Extrapolating from a standardized definition of primary angiitis of the central nervous system, we defined CV as worsened neurological symptoms associated with compatible imaging. All images were analyzed by a radiologist, and two neurologists reviewed all inconclusive cases of suspected CV for adjudication. Factors associated with CV were analyzed, including dexamethasone use. A subgroup analysis was limited to patients with a lumbar puncture at PM diagnosis. RESULTS: Among 168 patients with PM, 49 (29.2%) had CV, occurring after a median of 8 days (IQR 5-13) of PM diagnosis. In multivariate analysis (N = 151), initial CRP was associated with CV (OR 1.28 per 50-unit increase, p = 0.003), which was marginally linked with delayed hospital admission more than 48 hours after first symptoms (OR 2.39, p = 0.06) and prior NSAID intake (OR 2.94, p = 0.05). Dexamethasone administration did not impact CV occurrence. In 133 patients having undergone lumbar puncture, CSF protein level > 4.4 g/L (OR 4.50, p = 0.006) was associated with CV. CONCLUSIONS: In our cohort, CV was a frequent and severe complication of PM, often occurring in association with unduly delayed medical care, high CRP at admission, and high levels of protein in CSF.
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Meningite Pneumocócica , Vasculite do Sistema Nervoso Central , Adulto , Humanos , Estudos de Coortes , Dexametasona/uso terapêutico , Meningite Pneumocócica/complicações , Meningite Pneumocócica/tratamento farmacológico , Meningite Pneumocócica/epidemiologia , Vasculite do Sistema Nervoso Central/complicações , Vasculite do Sistema Nervoso Central/tratamento farmacológicoRESUMO
OBJECTIVE: Evaluate whether prefrail and frail people with HIV (PWH) have a higher risk of cognitive impairment on screens. METHODS: Analysis of PWH aged 70 or older included in the ANRS EP66 SEPTAVIH cohort, on antiretroviral therapy for at least 12âmonths and with a MoCA test at enrolment. Adjusted risk of a Montreal Cognitive Assessment (MoCA) less than 26 was compared in frail/prefrail versus robust PWH. RESULTS: A total of 503 PWH were enrolled with a median age of 73âyears, IQR [71-77], 81.5% were male, 73.8% were French natives, 32.9% had low socio-economic status (EPICES score >30.2), and 41.3% were college graduates; 27.3% had a history of clinical AIDS. A total of 294 (58.5%) PWH had a MoCA score less than 26; 182 (36%) a MoCA score 23 or less. Frailty, prefrailty and robustness were found in 13.1, 63.6 and 23.3% participants, respectively. PWH with a MoCA less than 26 had a significantly higher risk of being frail/prefrail, this before [odds ratio (OR)â=â2.31; 95% confidence interval (CI) 1.50-3.57], and after adjustment for confounders (ORâ=â1.80; 95% CI 1.07-3.01). The risk of being frail/prefrail in patients with a MoCA 23 or less was higher (adjusted ORâ=â2.75; 95% CI 1.46-5.16). Other factors independently associated with a MoCA less than 26 were older age, birth outside of France and a lower education level and being diabetic. CONCLUSION: Abnormal MoCA screens were frequent in our cohort of PWH aged 70 or older with controlled HIV disease. Cognitive impairment should be systematically screened in frail/prefrail PWH. Frailty/prefrailty, diabetes and social factors, but not HIV-related factors, are important determinants of cognitive function in PWH with controlled disease.
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Disfunção Cognitiva , Fragilidade , Infecções por HIV , Idoso , Humanos , Masculino , Feminino , Fragilidade/diagnóstico , Idoso Fragilizado , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Disfunção Cognitiva/diagnóstico , FenótipoRESUMO
OBJECTIVES: We aimed to examine the association of the country of birth and the other patients' characteristics with the prescription of two-drug regimens (2DRs) in virally suppressed people with HIV (PWH) in France. DESIGN: Observational study conducted from the national Dat'AIDS prospectively collected database. METHODS: We included all adults who were actively in care on 31 December 2020 in 26 French centers, with an HIV plasma viral load (pVL) <50âcopies/ml for at least 6âmonths while on antiretroviral therapy (ART). Patients with chronic hepatitis B were excluded because they are not eligible to 2DRs. Univariate and multivariate logistic regressions were built to analyze relationships between patients' characteristics and receiving a 2DR. RESULTS: We analyzed data from 28 395 PWH: 41.7% men who have sex with men, 31.7% women and 26.5% heterosexual men; 35% born abroad. Median age was 53âyears [interquartile range (IQR) 44-60]; ART duration 14âyears (8-23); duration of virological suppression 87âmonths (42-142). 2DRs (mainly dolutegravir/rilpivirine, 53.8%, or dolutegravir/lamivudine, 41.7%) were prescribed in 16.3% of the patients and were less common in the 'born abroad' group (18.9% versus 11.5%). The multivariate model showed that individuals born in France were more likely to receive a 2DR [adjusted odds ratio (aOR): 1.62 [1.50-1.74]], independently of other characteristics. Older PLWH and those with higher CD4 + T-cell counts were also more likely to receive a 2DR. CONCLUSION: Despite unrestricted access to ART in France, independently from HIV disease parameters, PWH born abroad were less likely to receive 2DRs as a maintenance regimen than those born in France. Qualitative data are needed to better understand physicians' prescribing practices.
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Fármacos Anti-HIV , Infecções por HIV , Minorias Sexuais e de Gênero , Adulto , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Homossexualidade Masculina , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Oxazinas/uso terapêutico , Piridonas/uso terapêutico , França , Prescrições , Carga ViralRESUMO
OBJECTIVES: We aimed to describe factors associated with the choice of first antiretroviral therapy (ART) in persons with HIV (PWH) in France, included the country of birth, as well as the time to undetectable viral load and treatment discontinuation. DESIGN: Observational study conducted from the national Dat'AIDS prospectively collected database. METHODS: We included all adults who started their first ART between 01 January 2014 and 31 December 2020, with a pretherapeutic plasma viral load (pVL) at least 400âcopies/ml. Univariable and multivariable logistic regressions were used to analyze PWH characteristics driving to an integrase strand transfer inhibitors (INSTI)-based first prescribed regimen. We also analyzed time to first line discontinuation, and to a first undetectable pVL, using Kaplan-Meier model. RESULTS: We analyzed data from 9094 PWH: 45% MSM, 27% women and 27% heterosexual men; 48% born abroad; 4.7 and 2.8% with concomitant hepatitis B and tuberculosis, respectively. INSTIs were prescribed as first-line therapy in 50% of PWH, which increased over time. Native French PWH were more likely to receive an INSTI-based regimen than PWH born abroad [adjusted prevalence ratio 1.47, 95% confidence interval (CI) 1.33-1.60], as were high pVL at diagnosis, hepatitis B or concomitant tuberculosis. Time before discontinuation of the first ART and reaching a first undetectable pVL was not different according to the place of birth. CONCLUSION: Despite unrestricted access to INSTIs in France, independently from HIV disease parameters, PWH born abroad received INSTIs less frequently as a first regimen than those born in France. Qualitative data are needed to better understand physicians' prescribing practices.
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Infecções por HIV , Inibidores de Integrase de HIV , Hepatite B , Minorias Sexuais e de Gênero , Adulto , Masculino , Humanos , Feminino , Infecções por HIV/complicações , Homossexualidade Masculina , Inibidores de Integrase de HIV/uso terapêutico , Antirretrovirais/uso terapêutico , França/epidemiologia , Carga Viral , Hepatite B/complicaçõesRESUMO
OBJECTIVE: To compare the estimated glomerular filtration rate (eGFR) using the creatinine equation (eGFRcreat) or the cystatin C equation (eGFRcys) in people with HIV (PWH) under antiretroviral drugs. We specifically included patients with an eGFRcreat around 60âml/min per 1.73âm2 to evaluate agreement on stage 2 and 3 chronic kidney disease (CKD) classification. DESIGN: eGFRcreat, eGFRcys and resulting CKD staging were determined in 262 consecutive patients with HIV-1 (PWH) with a suppressed viral load (<200âcopies/ml) under antiretroviral drugs and having impaired renal function (eGFRcreat between 45 and 80âml/min per 1.73âm2). Antiretroviral drugs regimens were classified into eight groups: cobicistat (COBI)+elvitegravir (EVG), ritonavir (RTV)+protease inhibitor, dolutegravir (DTG), DTG+rilpivirine (RPV), RPV, raltegravir (RAL), bictegravir (BIC), and other antiretroviral drugs. RESULTS: Mean eGFRcys was higher than mean eGFRcreat (77.7â±â0.5 vs. 67.9ââ±â7.9âml/min per 1.73âm2, Pâ<â0.0001). The differences were significant in five treatment groups with COBI/EVG; DTG; DTG+RPV; RPV; RAL. CKD classification was modified for 51% of patients when using eGFRcys instead of eGFRcreat, with reclassification to less severe stages in 37% and worse stages in 14%. CONCLUSION: This study highlighted significant differences in eGFR depending on the renal marker used in PWH, having a significant impact on CKD classification. eGFRcys should be an additive tool for patients having eGFRcreat around 60âml/min per 1.73âm2 for better identification of renal impairment.
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Infecções por HIV , Insuficiência Renal Crônica , Humanos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Creatinina , Cistatina C , Taxa de Filtração Glomerular , Antirretrovirais/uso terapêutico , Cobicistat/uso terapêutico , Rim/fisiologiaRESUMO
BACKGROUND: A previous study showed an association between CD4 T-cell count decline in people with human immunodeficiency virus infection (PWH) with viral suppression and an increased risk of severe morbid conditions. We aimed to assess the risk of CD4 T-cell count decline (hereafter, CD4 decline), determine associated factors, and evaluate the association of this decline with the risk of severe morbid conditions (cardiovascular disease and cancer) or death. METHODS: From the Agence Nationale de Recherches sur le SIDA et les hépatites virales (ANRS) CO4 French Hospital Database on HIV cohort, we selected PWH >18 years old who had been followed up for ≥2 years after viral suppression following the initiation of combination antiretroviral therapy (cART) between 2006 and 2018. CD4 decline was defined as 2 consecutive relative differences ≥15%. Among participants with such decline, we modeled CD4, CD8, and total lymphocyte counts before and after CD4 decline, using spline regression. The remaining objectives were assessed using Poisson regression, with the association between CD4 decline and the risk of severe morbid conditions or death evaluated during or after 6 months of decline. RESULTS: Among 15 714 participants (75 417 person-years), 181 presented with CD4 decline (incidence rate, 2.4/1000 person-years (95% confidence interval, 2.1-2.8). CD8 and total lymphocyte counts also showed a similar decline. Older current age and lower viral load at treatment initiation were associated with the risk of CD4 decline. The risk of severe morbid conditions or death was 11-fold higher during the first 6 months for participants who presented with CD4 decline versus those who did not (incidence rate ratio, 10.8 [95% confidence interval, 5.1-22.8]), with no significant difference after 6 months. CONCLUSIONS: In PWH with viral suppression, CD4 decline was rare and related to global lymphopenia. It was associated with a higher risk of severe morbid conditions or death during the first 6 months.
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Fármacos Anti-HIV , Infecções por HIV , Humanos , Adolescente , Terapia Antirretroviral de Alta Atividade , Linfócitos T CD4-Positivos , Carga Viral , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Contagem de Linfócito CD4 , Fármacos Anti-HIV/uso terapêuticoRESUMO
OBJECTIVES AND DESIGN: Frailty is a phenotype associated with adverse health outcomes in older persons. It has been evaluated mainly in middle-aged persons with HIV (PWH). The French multicenter prospective ANRS EP66 SEPTAVIH study aimed to assess frailty prevalence and risk factors in PWH aged 70 years or older on antiretroviral treatment (ART) for at least 12âmonths. METHODS: At baseline, Fried frailty phenotype criteria, sociodemographic data, medical/HIV history, functional status, comorbidities, including impaired cognitive function, depression, history of falls, and co-medications were collected. We measured the prevalence of frailty and compared the characteristics of frail versus prefrail and robust participants using univariate (Kruskal-Wallis tests for continuous variables and Chi 2 tests for categorical variables) and multivariate analyses. RESULTS: Five hundred and ten PWH, mostly male (81.4%), were included with a median age of 73âyears. The median HIV and ART durations were 22.7âyears and 15.7âyears, respectively. The prevalence of frailty was 13.5%, and of prefrailty 63.3%. In the multivariate analysis, increasing age [odds ratio (OR) 1.79 for each 5-year increment; 95% confidence interval (CI) 1.32-2.41], deprived socioeconomic status (OR 3.17; 95% CI 1.76-5.70), and multimorbidities (three or more) (OR 2.03; 95% CI 1.06-3.90) were associated with frailty. CONCLUSION: A low prevalence of frailty was reported (13.5%) in PWH aged 70 years or older, whereas two-thirds of them were prefrail. Age, low socioeconomic status, and multimorbidities, but no HIV-related factors, were associated with frailty, suggesting the need to target these factors to help promoting successful aging in this population.
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Infecções por HIV , Masculino , Feminino , Humanos , Estudos Prospectivos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Baixo Nível Socioeconômico , Fatores de RiscoRESUMO
The assessment of mood disorders and addiction linked to the practice of chemsex is of interest given the psychoactive substances used. The aim of this study was to assess risky sexual and addictive behavior to chemsex and related anxiety/depression symptoms in individuals receiving HIV pre-exposure prophylaxis (PrEP). In this cross-sectional study, all adults presenting for PrEP renewal at French sexual health centers were enrolled from January 2018 to March 2019. Participants completed a questionnaire on chemsex (i.e., the use of psychoactive substances before/during sex), including adapted Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) to chemsex addiction (questions of ASSIST were modified to focus on chemsex). Anxiety/depression was assessed with the Hospital Anxiety and Depression Scale. In the last 3 months before enrollment, 39.8% (94/236) of participants reported chemsex. The main psychoactive substances consumed during chemsex were cathinones (74.6%), gamma-hydroxybutyrate (66.3%), and other psychostimulants (60%). The median score of the chemsex-focused ASSIST was 8 [IQR25-75 : 3-15]; 72.2% of participants had a score justifying at least a brief intervention (>4). In multivariate analyses, anxiety and cathinones consumption were associated with an ASSIST score >4: OR 13.65 (95% CI 1.68-662.7), P = 0.0062, and OR 8.468 (95% CI 2.066-43.059), P = 0.0014, respectively. The level of addiction to the practice of chemsex can be difficult to estimate for the user, and the ASSIST makes it possible to evaluate this addiction and to direct the subjects toward specialized consultations of addictology, sexual health, or PrEP renewals. The implementation of the modified ASSIST in these consultations can allow early systematic screening and counseling.
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Comportamento Aditivo , Infecções por HIV , Profilaxia Pré-Exposição , Transtornos Relacionados ao Uso de Substâncias , Adulto , Masculino , Humanos , Homossexualidade Masculina/psicologia , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Transtornos do Humor/prevenção & controle , Estudos Transversais , Transtornos Relacionados ao Uso de Substâncias/prevenção & controleRESUMO
BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease with increased risk of infections. Here, we assessed whether pSS patients were at higher risk of hospitalization for community and opportunistic infections. METHODS: We selected newly hospitalized pSS patients between 2011 and 2018, through a nationwide population-based retrospective study using the French Health insurance database. We compared the incidence of hospitalization for several types of infections (according to International Classification for Disease codes, ICD-10) between pSS patients and an age- and sex-matched (1:10) hospitalized control group. We calculated adjusted Hazard Ratios (aHR, 95% CI) adjusted on socio-economic status, past cardiovascular or lung diseases and blood malignancies factors. RESULTS: We compared 25 661 pSS patients with 252 543 matched patients. The incidence of hospitalizations for a first community infection was increased in pSS patients [aHR of 1.29 (1.22-1.31), p < .001]. The incidence of hospitalization for bronchopulmonary infections was increased in pSS patients [aHR of 1.50 (1.34-1.69), p < .001, for pneumonia]. Hospitalizations for pyelonephritis and intestinal infections were increased [aHR of 1.55 (1.29-1.87), p < .001 and 1.18 (1.08-1.29), p < .001, respectively]. Among opportunistic infections, only zoster, and mycobacteria infections (tuberculosis and non-tuberculous) were at increased risk of hospitalization [aHR of 3.32 (1.78-6.18), p < .001; 4.35 (1.41-13.5), p = .011 and 2.54 (1.27-5.06), p = .008, respectively]. CONCLUSIONS: pSS patients are at higher risk of hospitalization for infections. The increased risk of hospitalization for mycobacterial infections illustrates the potential bilateral relationship between the two conditions. Vaccination against respiratory pathogens and herpes zoster virus may help prevent some hospitalizations in pSS patients.KEY MESSAGESPrimary Sjögren's syndrome (pSS) increases hospitalization risk for community infections: bronchopulmonary, skin, dental, ear-nose-throat, intestinal infections and pyelonephritis.Hospitalizations for zoster and mycobacterial infections are also increased in this population.Dedicated preventive measures and vaccination campaigns could decrease the burden of infections in pSS patients.
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Herpes Zoster , Infecções Oportunistas , Pielonefrite , Síndrome de Sjogren , Estudos de Coortes , Herpes Zoster/epidemiologia , Hospitalização , Humanos , Estudos Retrospectivos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/epidemiologiaRESUMO
The role of immune checkpoints (ICPs) in both anti-HIV T cell exhaustion and HIV reservoir persistence, has suggested that an HIV cure therapeutic strategy could involve ICP blockade. We studied the impact of anti-PD-1 therapy on HIV reservoirs and anti-viral immune responses in people living with HIV and treated for cancer. At several timepoints, we monitored CD4 cell counts, plasma HIV-RNA, cell associated (CA) HIV-DNA, EBV, CMV, HBV, HCV, and HHV-8 viral loads, activation markers, ICP expression and virus-specific T cells. Thirty-two patients were included, with median follow-up of 5 months. The CA HIV-DNA tended to decrease before cycle 2 (p = 0.049). Six patients exhibited a ≥0.5 log10 HIV-DNA decrease at least once. Among those, HIV-DNA became undetectable for 10 months in one patient. Overall, no significant increase in HIV-specific immunity was observed. In contrast, we detected an early increase in CTLA-4 + CD4+ T cells in all patients (p = 0.004) and a greater increase in CTLA-4+ and TIM-3 + CD8+ T cells in patients without HIV-DNA reduction compared to the others (p ≤ 0.03). Our results suggest that ICP replacement compensatory mechanisms might limit the impact of anti-PD-1 monotherapy on HIV reservoirs, and pave the way for combination ICP blockade in HIV cure strategies.
Assuntos
Infecções por HIV , Neoplasias , Antivirais/uso terapêutico , Antígeno CTLA-4 , Infecções por HIV/metabolismo , Humanos , Imunidade , Imunoterapia , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1/metabolismoRESUMO
BACKGROUND: We aimed to evaluate the incidence rates between 2010 and 2015 for invasive cervical cancer (ICC), breast cancer (BC), and colorectal cancer (CRC) in people living with HIV (PLWH) in France, and to compare them with those in the French general population. These cancers are targeted by the national cancer-screening program. SETTING: This is a retrospective study based on the longitudinal data of the French Dat'AIDS cohort. METHODS: Standardized incidence ratios (SIR) for ICC and BC, and incidence rates for all three cancers were calculated overall and for specific sub-populations according to nadir CD4 cell count, HIV transmission category, HIV diagnosis period, and HCV coinfection. RESULTS: The 2010-2015 CRC incidence rate was 25.0 [95% confidence interval (CI): 18.6-33.4] per 100,000 person-years, in 44,642 PLWH (both men and women). Compared with the general population, the ICC incidence rate was significantly higher in HIV-infected women both overall (SIR = 1.93, 95% CI: 1.18-3.14) and in the following sub-populations: nadir CD4 ≤ 200 cells/mm3 (SIR = 2.62, 95% CI: 1.45-4.74), HIV transmission through intravenous drug use (SIR = 5.14, 95% CI: 1.93-13.70), HCV coinfection (SIR = 3.52, 95% CI: 1.47-8.47) and HIV diagnosis before 2000 (SIR = 2.06, 95% CI: 1.07-3.97). Conversely, the BC incidence rate was significantly lower in the study sample than in the general population (SIR = 0.56, 95% CI: 0.42-0.73). CONCLUSION: The present study showed no significant linear trend between 2010 and 2015 in the incidence rates of the three cancers explored in the PLWH study sample. Specific recommendations for ICC screening are still required for HIV-infected women and should focus on sub-populations at greatest risk.
Assuntos
Neoplasias da Mama , Coinfecção , Neoplasias Colorretais , Infecções por HIV , Hepatite C , Neoplasias do Colo do Útero , Neoplasias da Mama/complicações , Neoplasias da Mama/epidemiologia , Coinfecção/epidemiologia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/epidemiologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hepatite C/complicações , Hepatite C/epidemiologia , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de Risco , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/epidemiologiaRESUMO
Aim: To optimize vaccination strategy, evidence on vaccine efficacy against COVID-19 is needed. Method: The present network meta-analysis uses reconstructed individual patient data from phase III trials on vaccine efficacy (VE), identified through MEDLINE, EMBASE, and Cochrane library (CENTRAL) peer-reviewed and published in English before August 31, 2021. The primary outcome was the VE against confirmed COVID-19 at any time after the first dose as defined in each study. VE was re-estimated using the two-stage approach. Poisson regression models were applied to each trial at the first stage, and the incidence risk ratio (IRR) and their 95% CI were aggregated to allow random-effects network meta-analysis (NMA) at the second stage. VE was expressed as: (1-IRR) × 100. The study protocol is registered in PROSPERO (CRD42020200012). Results: A total of eight studies, evaluating nine different vaccines were identified and analyzed. Between April 23, 2020 and January 05, 2021, 210,418 participants were recruited in 354 sites worldwide. During a median (IQR) follow-up duration of 69.8 (69.7-70.3) days, 2131 confirmed COVID-19 cases occurred (604; 26.0 per 1000 person-years in vaccine recipients and 1527; 85.9 per 1000 person-years in the control group). The mRNA-1273 vaccine was the most effective (P-score 0.99); at any time after dose 1, incidence reduction for mRNA-1273 ranged from 78% to 98% compared to the other vaccines. Conclusion: Our results provide evidence for the short-term superiority of mRNA vaccines, especially the mRNA-1273 vaccine in prevention of COVID-19 in different populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-022-01707-1.
RESUMO
OBJECTIVES: To assess the efficacy of inhaled ciclesonide in reducing the risk of adverse outcomes in COVID-19 outpatients at risk of developing severe illness. METHODS: COVERAGE is an open-label, randomized controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms for ≤7 days, and absence of criteria for hospitalization are randomly allocated to either a control arm or one of several experimental arms, including inhaled ciclesonide. The primary efficacy endpoint is COVID-19 worsening (hospitalization, oxygen therapy at home, or death) by Day 14. Other endpoints are adverse events, maximal follow-up score on the WHO Ordinal Scale for Clinical Improvement, sustained alleviation of symptoms, cure, and RT-PCR and blood parameter evolution at Day 7. The trial's Safety Monitoring Board reviewed the first interim analysis of the ciclesonide arm and recommended halting it for futility. The results of this analysis are reported here. RESULTS: The analysis involved 217 participants (control 107, ciclesonide 110), including 111 women and 106 men. Their median age was 63 years (interquartile range 59-68), and 157 of 217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days (interquartile range 3-5). During the 28-day follow-up, 2 participants died (control 2/107 [1.9%], ciclesonide 0), 4 received oxygen therapy at home and were not hospitalized (control 2/107 [1.9%], ciclesonide 2/110 [1.8%]), and 24 were hospitalized (control 10/107 [9.3%], ciclesonide 14/110 [12.7%]). In intent-to-treat analysis of observed data, 26 participants reached the composite primary endpoint by Day 14, including 12 of 106 (11.3%, 95% CI: 6.0%-18.9%) in the control arm and 14 of 106 (13.2%; 95% CI: 7.4-21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms. DISCUSSION: Our findings are consistent with the European Medicines Agency's COVID-19 task force statement that there is currently insufficient evidence that inhaled corticosteroids are beneficial for patients with COVID-19.