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BACKGROUND: Antiretroviral therapy (ART)-related weight gain is of particular concern in people with HIV (PWH). Although weight gain was observed among PWH receiving tenofovir alafenamide (TAF), little is known about the potential reversibility after TAF discontinuation. We evaluated weight and metabolic changes 12 months after TAF discontinuation in the Swiss HIV Cohort Study. METHODS: We included participants who received at least 6 months of TAF-containing ART between January 2016 and March 2023. Using multivariable mixed-effect models, changes in weight and lipid levels were compared between individuals who continued TAF and those who switched to one of the following TAF-free regimens: (1) tenofovir disoproxil fumarate (TDF)-based ART, (2) dolutegravir/lamivudine (DTG/3TC), or (3) long-acting cabotegravir/rilpivirine (CAB/RPV). RESULTS: Of 6555 participants (median age 54 years, 24.3% female, 13% Black), 5485 (83.7%) continued, and 1070 (16.3%) stopped TAF. Overall, discontinuing TAF was associated with an adjusted mean weight change of -0.54â kg (95% confidence interval [CI] -.98 to -.11) after 12 months. In stratified analyses, switching from TAF to TDF led to an adjusted mean weight decrease of -1.84â kg (95% CI -2.72 to -.97), and to a decrease in mean total cholesterol (-0.44â mmol/L) and triglycerides (-0.38â mmol/L) after 12 months. Switching from TAF-based ART to DTG/3TC (-0.17â kg, 95% CI -.82 to .48) or long-acting CAB/RPV (-0.64â kg, 95% CI -2.16 to .89) did not lead to reductions in weight. CONCLUSIONS: Replacing TAF with TDF in PWH led to a decrease in body weight and an improved lipid profile within 1 year. Weight changes were not observed among individuals who switched to DTG/3TC or long-acting CAB/RPV.
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Alanina , Fármacos Anti-HIV , Infecções por HIV , Tenofovir , Humanos , Feminino , Masculino , Infecções por HIV/tratamento farmacológico , Tenofovir/uso terapêutico , Tenofovir/administração & dosagem , Tenofovir/análogos & derivados , Pessoa de Meia-Idade , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Adulto , Aumento de Peso/efeitos dos fármacos , Adenina/análogos & derivados , Adenina/uso terapêutico , Adenina/administração & dosagem , Antropometria , Peso Corporal/efeitos dos fármacos , Estudos de Coortes , SuíçaRESUMO
BACKGROUND: The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so new vaccination strategies are needed in this population. METHODS: Adult SOT recipients from 9 transplant clinics in Switzerland and Spain were enrolled if they were >3 months after transplantation. Patients were randomized (1:1:1) to a MF59-adjuvanted or a high-dose vaccine (intervention), or a standard vaccine (control), with stratification by organ and time from transplant. The primary outcome was vaccine response rate, defined as a ≥4-fold increase of hemagglutination-inhibition titers to at least 1 vaccine strain at 28 days postvaccination. Secondary outcomes included polymerase chain reaction-confirmed influenza and vaccine reactogenicity. RESULTS: A total of 619 patients were randomized, 616 received the assigned vaccines, and 598 had serum available for analysis of the primary endpoint (standard, n = 198; MF59-adjuvanted, n = 205; high-dose, n = 195 patients). Vaccine response rates were 42% (84/198) in the standard vaccine group, 60% (122/205) in the MF59-adjuvanted vaccine group, and 66% (129/195) in the high-dose vaccine group (difference in intervention vaccines vs standard vaccine, 0.20; 97.5% confidence interval [CI], .12-1); P < .001; difference in high-dose vs standard vaccine, 0.24 [95% CI, .16-1]; P < .001; difference in MF59-adjuvanted vs standard vaccine, 0.17 [97.5% CI, .08-1]; P < .001). Influenza occurred in 6% of the standard, 5% in the MF59-adjuvanted, and 7% in the high-dose vaccine groups. Vaccine-related adverse events occurred more frequently in the intervention vaccine groups, but most of the events were mild. CONCLUSIONS: In SOT recipients, use of an MF59-adjuvanted or a high-dose influenza vaccine was safe and resulted in a higher vaccine response rate. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov NCT03699839.
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Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Transplante de Órgãos , Adulto , Humanos , Influenza Humana/prevenção & controle , Suíça , Anticorpos Antivirais , Polissorbatos/efeitos adversos , Esqualeno/efeitos adversos , Adjuvantes Imunológicos , Testes de Inibição da Hemaglutinação , Transplante de Órgãos/efeitos adversosRESUMO
BACKGROUND: The burden of herpes zoster (shingles) virus and associated complications, such as post-herpetic neuralgia, is higher in older adults and has a significant impact on quality of life. The incidence of herpes zoster and post-herpetic neuralgia is increased in people living with HIV (PLWH) compared to an age-matched general population, including PLWH on long-term antiretroviral therapy (ART) with no detectable viremia and normal CD4 counts. PLWH - even on effective ART may- exhibit sustained immune dysfunction, as well as defects in cells involved in the response to vaccines. In the context of herpes zoster, it is therefore important to assess the immune response to varicella zoster virus vaccination in older PLWH and to determine whether it significantly differs to that of HIV-uninfected healthy adults or younger PLWH. We aim at bridging these knowledge gaps by conducting a multicentric, international, non-randomised clinical study (SHINGR'HIV) with prospective data collection after vaccination with an adjuvant recombinant zoster vaccine (RZV) in two distinct populations: in PLWH on long-term ART (> 10 years) over 50 years of and age/gender matched controls. METHODS: We will recruit participants from two large established HIV cohorts in Switzerland and in France in addition to age-/gender-matched HIV-uninfected controls. Participants will receive two doses of RZV two months apart. In depth-evaluation of the humoral, cellular, and innate immune responses and safety profile of the RZV will be performed to address the combined effect of aging and potential immune deficiencies due to chronic HIV infection. The primary study outcome will compare the geometric mean titer (GMT) of gE-specific total IgG measured 1 month after the second dose of RZV between different age groups of PLWH and between PLWH and age-/gender-matched HIV-uninfected controls. DISCUSSION: The SHINGR'HIV trial will provide robust data on the immunogenicity and safety profile of RZV in older PLWH to support vaccination guidelines in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05575830. Registered on 12 October 2022. Eu Clinical Trial Register (EUCT number 2023-504482-23-00).
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Infecções por HIV , Vacina contra Herpes Zoster , Herpes Zoster , Neuralgia Pós-Herpética , Humanos , Pessoa de Meia-Idade , Idoso , Neuralgia Pós-Herpética/prevenção & controle , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Qualidade de Vida , Herpes Zoster/epidemiologia , Herpesvirus Humano 3 , Vacinas Sintéticas , Imunidade , Estudos Multicêntricos como AssuntoRESUMO
HIV pre-exposure prophylaxis (PrEP) is an effective tool in HIV prevention but is rarely prescribed by primary care physicians. A survey conducted among 147 physicians to assess their knowledge and interest in prescribing PrEP shows that 97% stated they have already heard of PrEP, but their knowledge of its indications, dosage, price, and side-effects is often incomplete or incorrect. For 69% of them, the main obstacle to prescribing PrEP is the lack of training on the subject. However, 70% of physicians express interest in receiving training to confidently prescribe PrEP to their patients. To address this demand, the clinical recommendations of the SwissPrEPared program are summarized.
La prophylaxie pré-exposition au VIH (PrEP) est un outil efficace dans la prévention du VIH mais rarement prescrite par les médecins de premier recours. Un sondage mené auprès de 147 médecins pour évaluer leurs connaissances et intérêt à prescrire la PrEP indique que 97 % déclarent avoir déjà entendu parler de la PrEP, mais aussi que leurs connaissances quant aux indications, posologie, prix et effets secondaires restent souvent lacunaires ou erronées. Pour 69 % des sondés, le principal obstacle à la prescription de la PrEP est le manque de formation sur le sujet. Cependant, 70 % des médecins se disent intéressés à être formés afin de prescrire la PrEP en toute confiance à leurs patients. Pour répondre à cette demande, les recommandations cliniques du programme SwissPrEPared sont résumées.
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Infecções por HIV , Médicos , Profilaxia Pré-Exposição , Humanos , Conhecimento , Infecções por HIV/prevenção & controleRESUMO
Alveolar echinococcosis is a rare but severe parasitic disease and is now in Europe the parasitic infection associated with the most morbidity and mortality. Its prevalence is increasing in Switzerland in both urban and rural areas. Echinococcosis is a differential diagnosis that should be considered when facing a cystic hepatic lesion. Moreover, this parasitic infection is increasing amongst immunocompromised patients, making the diagnosis more complex, because of atypic lesions and a more rapid evolution. At the current time, several treatment options, both surgical and medical, can offer patients a good prognosis and maintain a good quality of life.
L'échinococcose alvéolaire est une parasitose rare mais sévère. En Europe, il s'agit de l'infection parasitaire causant le plus de morbimortalité. Son incidence est en augmentation en Suisse dans les zones urbaines et rurales. L'échinococcose est donc un diagnostic différentiel à évoquer face à une lésion kystique hépatique. En outre, cette infection parasitaire est en augmentation chez les patients immunosupprimés, chez qui le diagnostic est plus complexe en raison de lésions atypiques et d'une évolution plus rapide. À l'heure actuelle, plusieurs modalités de traitements chirurgicaux et médicamenteux permettent d'offrir un bon pronostic aux patients tout en maintenant une bonne qualité de vie.
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Equinococose Hepática , Equinococose , Humanos , Equinococose Hepática/diagnóstico , Equinococose Hepática/epidemiologia , Equinococose Hepática/terapia , Qualidade de Vida , Equinococose/diagnóstico , Equinococose/epidemiologia , Equinococose/terapiaRESUMO
BACKGROUND: After mild COVID-19, some outpatients experience persistent symptoms. However, data are scarce and prospective studies are urgently needed. OBJECTIVES: To characterize the post-COVID-19 syndrome after mild COVID-19 and identify predictors. PARTICIPANTS: Outpatients with symptoms suggestive of COVID-19 with (1) PCR-confirmed COVID-19 (COVID-positive) or (2) SARS-CoV-2 negative PCR (COVID-negative). DESIGN: Monocentric cohort study with prospective phone interview between more than 3 months to 10 months after initial visit to the emergency department and outpatient clinics. MAIN MEASURES: Data of the initial visits were extracted from the electronic medical file. Predefined persistent symptoms were assessed through a structured phone interview. Associations between long-term symptoms and PCR results, as well as predictors of persistent symptoms among COVID-positive, were evaluated by multivariate logistic regression adjusted for age, gender, smoking, comorbidities, and timing of the survey. KEY RESULTS: The study population consisted of 418 COVID-positive and 89 COVID-negative patients, mostly young adults (median age of 41 versus 36 years in COVID-positive and COVID-negative, respectively; p = 0.020) and healthcare workers (67% versus 82%; p = 0.006). Median time between the initial visit and the phone survey was 150 days in COVID-positive and 242 days in COVID-negative patients. Persistent symptoms were reported by 223 (53%) COVID-positive and 33 (37%) COVID-negative patients (p = 0.006) and proportions were stable among the periods of the phone interviews. Overall, 21% COVID-positive and 15% COVID-negative patients (p = 0.182) attended care for this purpose. Four surveyed symptoms were independently associated with COVID-19: fatigue (adjusted odds ratio 2.14, 95% CI 1.04-4.41), smell/taste disorder (26.5, 3.46-202), dyspnea (2.81, 1.10-7.16), and memory impairment (5.71, 1.53-21.3). Among COVID-positive, female gender (1.67, 1.09-2.56) and overweight/obesity (1.67, 1.10-2.56) were predictors of persistent symptoms. CONCLUSIONS: More than half of COVID-positive outpatients report persistent symptoms up to 10 months after a mild disease. Only 4 of 14 symptoms were associated with COVID-19 status. The symptoms and predictors of the post-COVID-19 syndrome need further characterization as this condition places a significant burden on society.
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COVID-19 , Adulto , COVID-19/complicações , COVID-19/epidemiologia , Estudos de Coortes , Feminino , Humanos , Pacientes Ambulatoriais , Estudos Prospectivos , SARS-CoV-2 , Adulto Jovem , Síndrome de COVID-19 Pós-AgudaRESUMO
Shingles vaccination and pneumococcal vaccination of patients with celiac disease are among the most recent updates for the vaccination of vulnerable adults, in Switzerland. Shingles and especially post-herpes zoster pain remain an unresolved public health issue. The only vaccine available in Switzerland is very little administered because it is not reimbursed by health insurance companies. A second shingles vaccine is announced for 2022 and should help to reduce the burden of this disease. It has been known for many years that celiac disease is accompanied by hyposplenism in adults. The resulting increased risk of invasive pneumococcal infections justifies, since 2020, a recommendation for vaccination against these encapsulated bacteria.
La vaccination contre le zona et la vaccination contre les pneumocoques des patients souffrant de maladie cÅliaque font partie des mises à jour les plus récentes pour la vaccination de l'adulte vulnérable, en Suisse. Le zona et surtout les douleurs postzostériennes restent un problème de santé publique non résolu. Le seul vaccin disponible en Suisse est très peu administré en raison de son non-remboursement par les caisses-maladie. Un deuxième vaccin contre le zona est annoncé pour 2022 et devrait contribuer à alléger le fardeau de cette maladie. On sait depuis de nombreuses années que la maladie cÅliaque s'accompagne d'un hyposplénisme chez l'adulte. Le risque accru d'infections invasives à pneumocoques qui en découle justifie, depuis 2020, une recommandation de vaccination contre ces bactéries encapsulées.
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Vacina contra Herpes Zoster , Herpes Zoster , Vacinas , Adulto , Herpes Zoster/epidemiologia , Herpes Zoster/prevenção & controle , Humanos , Suíça/epidemiologia , VacinaçãoRESUMO
Long-acting cabotegravir has been studied mainly in the stringent framework of clinical trials, which does not necessarily reflect the situation of people with HIV (PWH) in routine clinical settings. The present population pharmacokinetic analysis aims to build real-world reference percentile curves of cabotegravir concentrations, accounting for patient-related factors that may affect cabotegravir exposure. The second objective is to simulate whether dosing interval adjustments of cabotegravir could be considered in specific subpopulations. Overall, 238 PWH contributed to 1,038 cabotegravir levels (186 during the initial oral administration phase and 852 after intramuscular injection). Cabotegravir pharmacokinetics was best described using a one-compartment model with distinct first order-absorption for oral and intramuscular administrations, and identical volume and clearance. Our model showed almost 40% faster absorption and 30% higher clearance than previously reported, resulting in a time to steady-state of 8 months and an elimination half-life of 4.6 weeks for long-acting cabotegravir. Sex and body mass index significantly influenced absorption, and bodyweight affected clearance. Model-based simulations showed that cabotegravir trough concentrations in females were 25% lower 4 weeks after the intramuscular loading dose, but 42% higher during the late maintenance phase. Finally, simulations indicated that in females, despite significantly higher cabotegravir concentrations, longer intervals between injections may not consistently ensure levels above the 4-fold protein-adjusted 90% inhibitory target concentration.
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Infecções por HIV , Modelos Biológicos , Piridonas , Humanos , Injeções Intramusculares , Feminino , Masculino , Infecções por HIV/tratamento farmacológico , Piridonas/farmacocinética , Piridonas/administração & dosagem , Adulto , Administração Oral , Pessoa de Meia-Idade , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/administração & dosagem , Meia-Vida , Preparações de Ação Retardada/farmacocinética , Adulto Jovem , Idoso , DicetopiperazinasRESUMO
Background: The efficacy and tolerability of long-acting cabotegravir and rilpivirine were demonstrated in Phase III trials. However, low concentrations combined with other risk factors have been associated with an increased risk of virologic failure. This study aims to verify whether drug concentrations measured in a real-world setting are consistent with those previously reported. Methods: SHCS-879 is a nationwide observational study within the Swiss HIV Cohort Study for the monitoring of people with HIV (PWH) on long-acting cabotegravir plus rilpivirine. Samples were collected from March 2022 to March 2023. Findings: Overall, 725 samples were obtained from 186 PWH. Our data show a large inter-individual variability in cabotegravir and rilpivirine concentrations, with some individuals exhibiting repeatedly low concentrations. Rilpivirine trough concentrations were consistent with those from Phase III trials, while cabotegravir concentrations were lower. The first concentrations quartile was only slightly above the target of 664 ng/mL. Exploratory statistical analyses found 35% (p < 0·01) lower cabotegravir trough in males compared to females. Overall, 172 PWH (92%) remained suppressed and three experienced virologic failures (1·6%), of those, two had sub-optimal drug exposure. No association was found between low trough levels and detectable viral load. Interpretation: Real-world cabotegravir concentrations are substantially lower than previously reported. However, these concentrations appear sufficient to ensure sustained virological suppression in almost every PWH. These reassuring data challenge the rather conservative thresholds adopted to date, which may raise unnecessary concerns. Yet, our study reveals that some PWH have repeatedly very low drug levels, for reasons that remain to be elucidated. Funding: This work was funded by the Swiss National Science Foundation, grant number N⦠324730_192449. This study received no support from pharmaceutical industries. This study was performed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project #879, and by the SHCS research foundation. The SHCS data were gathered by the Five Swiss University Hospitals, two Cantonal Hospitals, 15 affiliated hospitals and 36 private physicians (listed in http://www.shcs.ch/180-health-care-providers).
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BACKGROUND: We previously reported an increase in meropenem prescriptions for Pseudomonas aeruginosa infections in our hospital after the implementation of the 10th version of the EUCAST breakpoints table for P. aeruginosa in January 2020. As a consequence, antibiotic susceptibility testing results were adapted by masking meropenem for P. aeruginosa isolates susceptible to either ceftazidime, cefepime or piperacillin-tazobactam. We aimed to assess the changes in meropenem prescriptions after the implementation of the selective reporting. METHODS: In this retrospective single-centre observational study, we analysed antimicrobial therapies prescribed for P. aeruginosa infections after the susceptibility testing results have been made available over three periods: "before EUCAST update", "after EUCAST update without selective reporting" and "after EUCAST update with selective reporting", at Lausanne University Hospital, Switzerland. We collected epidemiological, microbiological and clinical data. The primary outcome was the prescription of meropenem to treat P. aeruginosa infections after the release of susceptibility testing results. Secondary outcomes were the use of increased dosage of non-meropenem anti-pseudomonal drugs, and IDs' consultations rates after the release of susceptibility testing results. RESULTS: Among the 457 patients included, 65 (14.2%) received meropenem: 5/148 (3.4%) before EUCAST update, 51/202 (25.3%) after EUCAST update without selective reporting, and 9/107 (8.4%) after EUCAST update with selective reporting. Supervision and counselling from IDs as well as the use of increased dosages of non-carbapenem antibiotics increased in both periods after EUCAST update, compared to the first period, respectively: 40.5% (60/148) versus 61.4% (124/202) versus 51.4% (55/107) (P < 0.001), and 57.9% (84/148) versus 91.1% (183/202) versus 90.7% (97/107) (P < 0.001). CONCLUSIONS: Selective reporting of antibiotic susceptibility testing results might decrease unnecessary meropenem prescriptions for the treatment of P. aeruginosa infections and could be part of multimodal antibiotic stewardship interventions.
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Antibacterianos , Infecções por Pseudomonas , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Meropeném/farmacologia , Meropeném/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Estudos Retrospectivos , Pseudomonas aeruginosa , HospitaisRESUMO
OBJECTIVES: We aimed to evaluate the impact of the 10th version of European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints table, where most antipseudomonal drugs but meropenem are now categorised as "Susceptible, increased exposure" and labelled I, on meropenem prescription for Pseudomonas aeruginosa infections. METHODS: In this retrospective single-centre observational study, we analysed antimicrobial therapies prescribed after susceptibility testing in all consecutive adult patients treated for P. aeruginosa infections between 01.08.2019 and 30.07.2020 in Lausanne University Hospital, Switzerland. We collected epidemiological, microbiological, clinical data, antimicrobial therapy, and infectious diseases specialists (IDs) consultations' data. The primary outcome was the prescription of meropenem to treat P. aeruginosa infections after release of susceptibility testing results. Secondary outcomes were: the use of increased dosage for non-meropenem anti-pseudomonal drugs, and IDs' consultations rates after susceptibility testing was made available. RESULTS: Among the 264 patients included, 40 (15.2%) received meropenem, 3.4% (5/148) before EUCAST update versus 30.2% (35/116) after (p < 0.001). Supervision and counselling from IDs and the use of increased dosages of non-carbapenem antibiotics also increased respectively (40.5% (60/148) vs 62.9% (73/116), P < 0.001); (55.5% (76/148) vs 88.9% (72/116), P < 0.001). Factors associated with these increments could not be adequately modelled. CONCLUSIONS: The change to 2020 EUCAST criteria might be associated with increased odds of meropenem prescription for the treatment of P. aeruginosa infections stressing the need of prescribers' education and the importance of antibiotic stewardship interventions.
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Infecções por Pseudomonas , Antibacterianos/uso terapêutico , Hospitais , Humanos , Meropeném/uso terapêutico , Testes de Sensibilidade Microbiana , Prescrições , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa , Estudos RetrospectivosRESUMO
BACKGROUND: The characteristics and outcomes of adult patients with respiratory syncytial virus (RSV) infection who require ICU admission are poorly defined. Although several studies in adults with RSV infection have been published in recent years, they did not focus specifically on patients with critical illness. RESEARCH QUESTION: What are the characteristics and outcomes of adult patients in the ICU with RSV infection and how do they compare with those of patients in the ICU with influenza infection? STUDY DESIGN AND METHODS: This retrospective, multicenter study in France and Belgium (17 sites) compared the characteristics and outcomes of adult patients in the ICU with RSV infection vs those with influenza infection between November 2011 and April 2018. Each patient with RSV infection was matched by institution and date of diagnosis with a patient with influenza infection. In-hospital mortality was compared between the two groups, with adjustment for prognostic factors in a multivariate model (sex, age, main underlying conditions, and concurrent bloodstream infection). RESULTS: Data from 618 patients (309 with RSV infection and 309 with influenza infection) were analyzed. Patients with RSV infection were significantly more likely to have an underlying chronic respiratory condition (60.2% vs 40.1%; P < .001) and to be immunocompromised (35% vs 26.2%; P = .02) than patients with influenza infection. Several differences in clinical signs and biological data at diagnosis were found between the groups. In-hospital mortality was not significantly different between the two groups (23.9% in the RSV group vs 25.6% in the influenza group; P = .63), even after adjustment for prognostic factors in a multivariate model. INTERPRETATION: Adult patients in the ICU with RSV infection differ from adult patients in the ICU with influenza in terms of comorbidities and characteristics at diagnosis. RSV infection was associated with high in-hospital mortality, approaching 25%. In multivariate analysis, RSV infection was associated with a similar odds of in-hospital death compared with influenza infection.
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Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Adulto , Estudos de Coortes , Mortalidade Hospitalar , Hospitalização , Humanos , Influenza Humana/complicações , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Unidades de Terapia Intensiva , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/epidemiologia , Estudos RetrospectivosRESUMO
SHCS#879 is an ongoing Switzerland-wide multicenter observational study conducted within the Swiss HIV Cohort Study (SHCS) for the prospective follow-up of people living with HIV (PLWH) receiving long-acting injectable cabotegravir-rilpivirine (LAI-CAB/RPV). All adults under LAI-CAB/RPV and part of SHCS are enrolled in the project. The study addresses an integrated strategy of treatment monitoring outside the stringent frame of controlled clinical trials, based on relevant patient characteristics, clinical factors, potential drug-drug interactions, and measurement of circulating blood concentrations. So far, 91 blood samples from 46 PLWH have been collected. Most individuals are less than 50 years old, with relatively few comorbidities and comedications. The observed concentrations are globally in accordance with the available values reported in the randomized clinical trials. Yet, low RPV concentrations not exceeding twice the reported protein-adjusted 90% inhibitory concentration have been observed. Data available at present confirm a considerable between-patient variability overall. Based on the growing amount of PK data accumulated during this ongoing study, population pharmacokinetic analysis will characterize individual concentration-time profiles of LAI-CAB/RPV along with their variability in a real-life setting and their association with treatment response and tolerability, thus bringing key data for therapeutic monitoring and precision dosage adjustment of this novel long-acting therapy.
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Viral infections account for up to 30% of all infectious complications in lung transplant recipients, remaining a significant cause of morbidity and even mortality. Impact of viral infections is not only due to the direct effects of viral replication, but also to immunologically-mediated lung injury that may lead to acute rejection and chronic lung allograft dysfunction. This has particularly been seen in infections caused by herpesviruses and respiratory viruses. The implementation of universal preventive measures against cytomegalovirus (CMV) and influenza (by means of antiviral prophylaxis and vaccination, respectively) and administration of early antiviral treatment have reduced the burden of these diseases and potentially their role in affecting allograft outcomes. New antivirals against CMV for prophylaxis and for treatment of antiviral-resistant CMV infection are currently being evaluated in transplant recipients, and may continue to improve the management of CMV in lung transplant recipients. However, new therapeutic and preventive strategies are highly needed for other viruses such as respiratory syncytial virus (RSV) or parainfluenza virus (PIV), including new antivirals and vaccines. This is particularly important in the advent of the COVID-19 pandemic, for which several unanswered questions remain, in particular on the best antiviral and immunomodulatory regimen for decreasing mortality specifically in lung transplant recipients. In conclusion, the appropriate management of viral complications after transplantation remain an essential step to continue improving survival and quality of life of lung transplant recipients.
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A 67-year-old man known with systemic sarcoidosis was admitted to the department of internal medicine because of cough and chest pain for several weeks. Thoracic tomodensitometry demonstrated multiple pulmonary nodules. Biopsies revealed features compatible with abscesses. Cultures and serologic tests were negative and the patient was successfully treated with prednisone. Three years later, a thoraco-abdominal tomodensitometry showed a relapse in the lung and also the apparition of similar lesions in the liver. Blood test revealed elevated CRP level at 40 mg/L and mild cholestasis. Biopsies of the liver excluded neoplastic or infectious diseases and showed inflammatory granulation tissue with abscess formation. A diagnosis of sarcoidosis-associated aseptic abscesses syndrome was then made, which was successfully treated with corticosteroids.