RESUMEN
BACKGROUND: There is an international epidemic of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men. Sustained virologic response (SVR) rates with pegylated interferon and ribavirin treatment are higher in these men during acute HCV than during chronic HCV, but treatment is still lengthy and SVR rates are suboptimal. METHODS: We performed a pilot study of combination therapy with telaprevir, pegylated interferon, and ribavirin in acute genotype 1 HCV infection in HIV-infected men. Men who were treated prior to the availability of, or ineligible for, telaprevir were the comparator group. The primary endpoint was SVR12, defined as an HCV viral load <5 IU/mL at least 12 weeks after completing treatment. RESULTS: In the telaprevir group, 84% (16/19) of men achieved SVR12 vs 63% (30/48) in the comparator group. Among men with SVR, median time to undetectable viral load was week 2 in the telaprevir group vs week 4 in the comparator group, and 94% vs 53% had undetectable viral loads at week 4. Most patients (81%) who achieved SVR in the telaprevir group received ≤12 weeks of treatment and there were no relapses after treatment. The overall safety profile was similar to that known for telaprevir-based regimens. CONCLUSIONS: Incorporating telaprevir into treatment of acute genotype 1 HCV in HIV-infected men halved the treatment duration and increased the SVR rate. Larger studies should be done to confirm these findings. Clinicians should be alert to detect acute HCV infection of HIV-infected men to take advantage of this effective therapy and decrease further transmission in this epidemic.
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Antivirales/uso terapéutico , Infecciones por VIH/virología , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Oligopéptidos/uso terapéutico , Adulto , Quimioterapia Combinada , Homosexualidad Masculina , Humanos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
Disseminated herpes simplex virus (HSV) infection during pregnancy is a rare, but potentially fatal condition. We present a case where prompt treatment with intravenous acyclovir resulted in a successful outcome for both mother and baby.
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The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in variants that can escape neutralization by therapeutic antibodies. Here, we describe AZD3152, a SARS-CoV-2-neutralizing monoclonal antibody designed to provide improved potency and coverage against emerging variants. AZD3152 binds to the back left shoulder of the SARS-CoV-2 spike protein receptor binding domain and prevents interaction with the human angiotensin-converting enzyme 2 receptor. AZD3152 potently neutralized a broad panel of pseudovirus variants, including the currently dominant Omicron variant JN.1 but has reduced potency against XBB subvariants containing F456L. In vitro studies confirmed F456L resistance and additionally identified T415I and K458E as escape mutations. In a Syrian hamster challenge model, prophylactic administration of AZD3152 protected hamsters from weight loss and inflammation-related lung pathologies and reduced lung viral load. In the phase 1 sentinel safety cohort of the ongoing SUPERNOVA study (ClinicalTrials.gov: NCT05648110), a single 600-mg intramuscular injection of AZD5156 (containing 300 mg each of AZD3152 and cilgavimab) was well tolerated in adults through day 91. Observed serum concentrations of AZD3152 through day 91 were similar to those observed with cilgavimab and consistent with predictions for AZD7442, a SARS-CoV-2-neutralizing antibody combination of cilgavimab and tixagevimab, in a population pharmacokinetic model. On the basis of its pharmacokinetic characteristics, AZD3152 is predicted to provide durable protection against symptomatic coronavirus disease 2019 caused by susceptible SARS-CoV-2 variants, such as JN.1, in humans.
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Anticuerpos Neutralizantes , COVID-19 , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Animales , SARS-CoV-2/efectos de los fármacos , Humanos , COVID-19/virología , Anticuerpos Neutralizantes/inmunología , Glicoproteína de la Espiga del Coronavirus/metabolismo , Cricetinae , Tratamiento Farmacológico de COVID-19 , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/farmacocinética , Mesocricetus , Femenino , Masculino , Adulto , Anticuerpos Antivirales/inmunología , Mutación/genética , Anticuerpos Monoclonales , Enzima Convertidora de Angiotensina 2/metabolismo , Carga Viral/efectos de los fármacosRESUMEN
Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome.
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COVID-19 , Adulto , Humanos , Dimetilfumarato/uso terapéutico , SARS-CoV-2 , Hospitalización , Hospitales , Resultado del TratamientoRESUMEN
SARS-CoV-2 has resulted in high levels of morbidity and mortality world-wide, and severe complications can occur in older populations. Humoral immunity induced by authorized vaccines wanes within 6 months, and frequent boosts may only offer transient protection. GRT-R910 is an investigational self-amplifying mRNA (samRNA)-based SARS-CoV-2 vaccine delivering full-length Spike and selected conserved non-Spike T cell epitopes. This study reports interim analyses for a phase I open-label dose-escalation trial evaluating GRT-R910 in previously vaccinated healthy older adults (NCT05148962). Primary endpoints of safety and tolerability were assessed. Most solicited local and systemic adverse events (AEs) following GRT-R910 dosing were mild to moderate and transient, and no treatment-related serious AEs were observed. The secondary endpoint of immunogenicity was assessed via IgG binding assays, neutralization assays, interferon-gamma ELISpot, and intracellular cytokine staining. Neutralizing antibody titers against ancestral Spike and variants of concern were boosted or induced by GRT-R910 and, contrasting to authorized vaccines, persisted through at least 6 months after the booster dose. GRT-R910 increased and/or broadened functional Spike-specific T cell responses and primed functional T cell responses to conserved non-Spike epitopes. This study is limited due to small sample size, and additional data from ongoing studies will be required to corroborate these interim findings.
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COVID-19 , ARN Mensajero/genética , COVID-19/prevención & control , Humanos , Anciano , Masculino , Femenino , Persona de Mediana Edad , Anciano de 80 o más Años , Ensayos Clínicos como Asunto , Anticuerpos Antivirales/inmunología , Anticuerpos Neutralizantes/inmunología , Linfocitos T/inmunologíaRESUMEN
We describe 3 individuals infected with human immunodeficiency virus with unusual focal brain syndromes; magnetic resonance imaging revealed "open-ring" pattern space occupying lesions. After deterioration while the patients were receiving anti-Toxoplasma therapy, brain biopsy was performed, which revealed aggressive demyelination consistent with tumefactive demyelination. Treatment with high-dose steroids resulted in complete recovery in all cases.
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Encefalopatías/virología , Edema Encefálico/virología , Enfermedades Desmielinizantes/virología , Infecciones por VIH/complicaciones , Adulto , Antirretrovirales/uso terapéutico , Encefalopatías/tratamiento farmacológico , Edema Encefálico/tratamiento farmacológico , Enfermedades Desmielinizantes/tratamiento farmacológico , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esteroides/uso terapéuticoAsunto(s)
Anticuerpos Monoclonales de Origen Murino/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Meningitis Criptocócica/inducido químicamente , Anciano , Cryptococcus neoformans/aislamiento & purificación , Humanos , Infliximab , Masculino , Rituximab , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
BACKGROUND: In patients with chronic hepatitis B, long-term use of lamivudine is limited by resistance mutations. Adefovir dipivoxil has a very low rate of resistance, but there have been recent reports describing resistance mutations. Tenofovir disoproxil fumarate and emtricitabine show potent activity against wild-type and lamivudine-resistant hepatitis B virus. METHODS: We describe a series of seven HIV-seronegative patients who failed to achieve undetectable hepatitis B viral DNA on adefovir. No lamivudine resistance testing was performed. The antiviral regimen was changed to tenofovir (300 mg daily) and emtricitabine (200 mg daily). Variables collected included levels of hepatitis B viral DNA by polymerase chain reaction, alanine and aspartate aminotransferase, hepatitis B e antigen and hepatitis B e antibody. RESULTS: The median hepatitis B viral DNA level while on adefovir was 430,000 copies/ml with a median fall in hepatitis B viral DNA levels of 2.0 log10 copies/ml. Patients were on adefovir for a median period of 10 months before a change in regimen to tenofovir and emtricitabine. This regimen change resulted in a median fall in hepatitis B viral DNA levels of 3.0 log10 copies/ml (range, 2-4) after a median treatment duration of 23 months (range, 14-28). All patients (100%) had achieved undetectable hepatitis B viral DNA levels following combination therapy. Anti-hepatitis B e seroconversion occurred in one patient. No change in serum creatinine was observed during therapy, and no significant adverse events were reported. CONCLUSIONS: In patients failing to respond to adefovir monotherapy or an adefovir-containing regimen for chronic hepatitis B virus, a combination of tenofovir and emtricitabine resulted in undetectable hepatitis B viral DNA levels without any renal toxicity. Tenofovir, in combination with emtricitabine, may be an alternative treatment for those with detectable hepatitis B viral DNA on adefovir.
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Adenina/análogos & derivados , Antivirales/uso terapéutico , Desoxicitidina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Organofosfonatos/uso terapéutico , Adenina/uso terapéutico , Adulto , ADN Viral/sangre , Desoxicitidina/uso terapéutico , Farmacorresistencia Viral , Quimioterapia Combinada , Emtricitabina , Femenino , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tenofovir , Resultado del TratamientoRESUMEN
PURPOSE: The use of maraviroc in our unit was reviewed with regard to efficacy and safety and also reviewed with regard to how our experience reflects the data presented in clinical trials. METHODS: We utilized the pharmacy dispensary system to identify any patient dispensed maraviroc and conducted a case note review. RESULTS: We identified 27 patients who have been prescribed maraviroc as part of their antiretroviral treatment. In all, 81% were men and 81% were white British. There were 26 treatment-experienced patients and 1 treatment-naive patient. At the time of switching to maraviroc, 17 patients had detectable HIV viral loads and 10 had HIV RNA levels <40 copies/mL. At completion, 6 undetectable patients maintained undetectability and 10 viremically detectable patients achieved viral suppression. Maraviroc was discontinued in 18.5% of patients and the only adverse drug reaction reported was a rash. CONCLUSIONS: The experience of using maraviroc by our study participants shows similarity in terms of efficacy and safety to the MERIT and MOTIVATE clinical trials.
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Ciclohexanos/uso terapéutico , Inhibidores de Fusión de VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Triazoles/uso terapéutico , Adulto , Recuento de Linfocito CD4 , Hipersensibilidad a las Drogas , Quimioterapia Combinada , Exantema/inducido químicamente , Femenino , VIH-1/genética , Humanos , Masculino , Maraviroc , Persona de Mediana Edad , ARN Viral/sangre , Estudios Retrospectivos , Carga Viral , Adulto JovenRESUMEN
Hepatoportal sclerosis (HPS) is one of several entities known to cause noncirrhotic portal hypertension. To date, its etiology is unknown. There have been increasing reports of HPS occurring in patients with human immunodeficiency virus (HIV), and the US Food and Drug Administration (FDA) recently issued an advisory regarding the development of noncirrhotic portal hypertension in association with didanosine (ddI) use. We report on a patient with HIV who had taken ddI for 4 years and who developed portal hypertension. Histopathological review of paired liver biopsies showed an initial drug hepatotoxicity, microvascular liver injury, and the presence of HPS. Despite cessation of ddI, the latter biopsy showed resolution of the drug-induced injury, but it also showed progression of the HPS. The patient's portal hypertension also progressed suggestive of an unremitting vascular injury. This case demonstrates the development of HPS resulting from a drug-induced microvascular injury. The paired biopsies demonstrate that the initial vascular injury may disappear but that the portal hypertension and HPS progress.
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Fármacos Anti-VIH/efectos adversos , Didanosina/efectos adversos , Hipertensión Portal/inducido químicamente , Hígado/patología , Infecciones por VIH/tratamiento farmacológico , Humanos , Hígado/efectos de los fármacos , Masculino , Persona de Mediana Edad , Sistema Porta/patología , EsclerosisRESUMEN
Outbreaks of acute hepatitis C virus (HCV) infection are occurring in HIV-infected men who have sex with men. We evaluated risk factors and liver histopathology in 11 consecutively enrolled men with newly acquired HCV infection that was diagnosed on the basis of antibody seroconversion, new elevations in alanine aminotransferase level, and wide fluctuations in HCV RNA level. Ten patients reported unprotected anal intercourse, and 7 reported "club-drug" use, including methamphetamine. Liver biopsy showed moderately advanced fibrosis (Scheuer stage 2) in 9 patients (82%). No cause of liver damage other than acute HCV infection was identified. The specific pathways leading to periportal fibrosis in HIV-infected men with newly acquired HCV infection require investigation.