RESUMEN
Rebound of SARS-CoV-2 shedding or COVID-19 signs and symptoms has been described after treatment with nirmatrelvir/ritonavir (Paxlovid). The direct association of nirmatrelvir/ritonavir to COVID-19 rebound remains unclear because most reports are based on individual cases or nonrandomized studies. Viral RNA shedding data from two phase 2/3, randomized, double-blind, placebo-controlled clinical trials of nirmatrelvir/ritonavir (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients [EPIC-HR] and Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients [EPIC-SR]) were analyzed to investigate the role of nirmatrelvir/ritonavir treatment in COVID-19 rebound. Rates of rebound of SARS-CoV-2 RNA shedding, identified based on an increase in nasopharyngeal viral RNA levels from day 5 (end-of-treatment) to day 10 or day 14, were similar between nirmatrelvir/ritonavir and placebo recipients. Among subjects with a virologic response through day 5, viral RNA rebound occurred in 6.4%-8.4% of nirmatrelvir/ritonavir recipients and 5.9%-6.5% of placebo recipients across EPIC-HR and the 2021/pre-Omicron and 2022/Omicron enrollment periods of EPIC-SR. Viral RNA rebound after nirmatrelvir/ritonavir treatment was not associated with COVID-19-related hospitalization or death. Data from randomized trials demonstrated that SARS-CoV-2 rebound can occur with or without antiviral treatment, supporting the Food and Drug Administration's determination of safety and efficacy of nirmatrelvir/ritonavir in eligible patients at high risk for severe COVID-19.
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COVID-19 , ARN Viral , Humanos , Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Péptido Hidrolasas , Ritonavir/uso terapéutico , SARS-CoV-2 , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Inactivated Polio Vaccines (IPV) and live Oral Polio Vaccine (OPV) were introduced in the mid-20th century, and their coordinated worldwide use led to almost complete elimination of the disease, with only one serotype of poliovirus remaining endemic in just two countries. Polio eradication will lead to discontinuation of OPV use and its replacement with IPV or other vaccines that are currently under development that will need to be tested in clinical trials. Despite decades of research, questions remain about the serological correlates of polio vaccine efficacy, specifically whether the vaccines are equally protective against immunologically different strains of the same serotype. The absence of significant morbidity does not allow use of a protection endpoint in clinical trials, so the answer could be obtained only by using surrogate markers such as immunogenicity. In this study, a panel of wild and vaccine-derived polioviruses of serotype 1 were tested in neutralization assays with sera from vaccine-immunized individuals. The results demonstrated that there was a significant difference in titers of neutralizing antibodies in human sera when measured against different strains. When measured with a homologous strain used for vaccine manufacture all subjects had detectable levels of antibodies, while neutralization tests with some heterologous strains failed to detect neutralizing antibodies in a number of subjects. Administration of a booster dose of IPV led to a significant increase in neutralizing titers against all strains. Results of the experiments using animal sera, performed to obtain more information on protectivity of neutralizing antibodies against heterologous strains, were consistent with the results obtained in the assays using human sera. These results are discussed in the context of serological biomarkers of protection against poliomyelitis, suggesting that potency of vaccines made from serologically different strains should be determined against both homologous and heterologous challenge viruses.
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Poliomielitis , Poliovirus , Animales , Humanos , Vacuna Antipolio Oral , Vacuna Antipolio de Virus Inactivados , Anticuerpos Neutralizantes , Variación AntigénicaRESUMEN
The landscape for the development of therapeutics for prevention and treatment of human immunodeficiency virus (HIV)-1 infection has pivoted towards long-acting antiretrovirals (LA-ARVs). LA-ARVs have the potential to transform global implementation of HIV-1 prevention and treatment strategies. The ability to identify potential knowledge gaps early in development, proactively address missing information or data gaps, and strategically leverage all the available information is the key to streamline the development of safe and effective LA-ARV therapeutics. The purpose of this article is to discuss some potential considerations for development of LA-ARVs. Three possible drug development scenarios are briefly discussed and include developing (1) a novel LA-ARV, (2) a novel LA formulation of an approved oral ARV, and (3) an LA pro-drug of an approved oral ARV. For each of these scenarios, we briefly describe what type(s) of information may be helpful and discuss potential opportunities to leverage available information. Additionally, we discuss some unique LA-ARV drug development considerations, including the use of an oral lead-in, and assessing the impact of residual ARV exposures on subsequent regimens and evaluation of LA-ARVs in specific populations. We strongly believe that efficient integration of multidisciplinary knowledge can advance the development, availability, and accessibility of therapeutics not only for HIV-1 prevention and treatment but also for other chronic viral infections.
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Infecciones por VIH , VIH-1 , Humanos , Salud Pública , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Antirretrovirales/uso terapéuticoRESUMEN
PURPOSE OF REVIEW: Outline some regulatory considerations and scientific challenges related to the development of long-acting antiretrovirals (ARVs) for the treatment and prevention of HIV-1 infection. RECENT FINDINGS: Poor adherence to oral ARV regimens continues to pose challenges for effective treatment and prevention of HIV-1 infection. The development of long-acting ARV modalities for treatment and prevention of HIV-1 infection is emerging as a promising alternative to the current treatment and prevention paradigm and has gained considerable interest. SUMMARY: The development of long-acting ARVs can present some unique drug development challenges. Advance planning and prioritization of studies early in development can facilitate the development of long-acting ARVs for the prevention and treatment of HIV-1 infection for all populations, including pediatric patients and pregnant women.
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Antirretrovirales , Preparaciones de Acción Retardada/administración & dosificación , Infecciones por VIH , Adolescente , Antirretrovirales/administración & dosificación , Antirretrovirales/uso terapéutico , Niño , Vías de Administración de Medicamentos , Implantes de Medicamentos/administración & dosificación , Implantes de Medicamentos/uso terapéutico , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , VIH-1/efectos de los fármacos , Humanos , Bombas de Infusión Implantables , Inyecciones , Cumplimiento de la Medicación , EmbarazoRESUMEN
Polioviruses are members of the Enterovirus C species and asymptomatic fecal shedding allows for their transmission and persistence in a community, as well as the emergence of vaccine-derived polioviruses. Using three serotype-specific real-time RT-PCR (rRT-PCR) assays, the shedding and circulation of oral poliovirus vaccine (OPV) strains was previously investigated in a prospective cohort of Mexican children, their contacts, and nearby sewage. Subsequently, a deep sequencing approach targeting the P1 genomic region was applied to characterize OPV strains previously detected by rRT-PCR. Amplifiable RNA was obtained for sequencing from 40.3% (58/144) of stool samples and 71.4% (15/21) of sewage using nucleic acids extracted directly from primary rRT-PCR-positive specimens. Sequencing detected one or more OPV serotypes in 62.1% (36/58) of stool and 53.3% (8/15) of sewage samples. All stool and sewage samples in which poliovirus was not detected by deep sequencing contained at least one non-polio enterovirus C (NPEV-C) strain. To improve screening specificity, a modified, two-step, OPV serotype-specific multiplex rRT-PCR was evaluated. In stool specimens, the overall agreement between the original assays and the multiplex was 70.3%. By serotype, the overall agreement was 95.7% for OPV serotype-1 (S1), 65.6% for S2, and 96.1% for S3. Furthermore, most original rRT-PCR positive/multiplex rRT-PCR negative results were collected in the summer and fall months, consistent with NPEV-C circulation patterns. In conclusion, this deep sequencing approach allowed for the characterization of OPV sequences directly from clinical samples and facilitated the implementation of a more specific multiplex rRT-PCR for OPV detection and serotyping.
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Secuenciación de Nucleótidos de Alto Rendimiento , Poliovirus/aislamiento & purificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Enterovirus Humano C/genética , Enterovirus Humano C/aislamiento & purificación , Heces/virología , Humanos , Poliovirus/genética , Estudios Prospectivos , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Serogrupo , Aguas del Alcantarillado/virologíaRESUMEN
BACKGROUND: Mexico introduced inactivated polio vaccine (IPV) into its routine immunization (RI) schedule in 2007 but continued to give trivalent oral polio vaccine (tOPV) twice a year during national health weeks (NHW) through 2015. OBJECTIVES: To evaluate individual variables associated with poliovirus (PV) shedding among children with IPV-induced immunity after vaccination with tOPV and their household contacts. MATERIALS AND METHODS: We recruited 72 children (both genders, ≤30 months, vaccinated with at least two doses of IPV) and 144 household contacts (both genders, 2 per household, children and adults) between 08/2010 and 09/2010 in Orizaba, Veracruz. Three NHW took place (one before and two after enrollment). We collected fecal samples monthly for 12 months, and tested 2500 samples for polioviruses types 1, 2 and 3 with three serotype-specific singleplex real-time RT-PCR (rRT-PCR) assays. In order to increase the specificity for OPV virus, all positive and 112 negative samples were also processed with a two-step, OPV serotype-specific multiplex rRT-PCR. ANALYSIS: We estimated adjusted hazard ratios (HR) and 95% CI using Cox proportional hazards regression for recurrent events models accounting for individual clustering to assess the association of individual variables with the shedding of any poliovirus for all participants and stratifying according to whether the participant had received tOPV in the month of sample collection. RESULTS: 216 participants were included. Of the 2500 collected samples, using the singleplex rRT-PCR assay, PV was detected in 5.7% (n = 142); PV1 in 1.2% (n = 29), PV2 in 4.1% (n = 103), and PV3 in 1.9% (n = 48). Of the 256 samples processed by multiplex rRT-PCR, PV was detected in 106 (PV1 in 16.41% (n = 42), PV2 in 21.09% (n = 54), and PV3 in 23.05% (n = 59). Both using singleplex and multiplex assays, shedding of OPV among non-vaccinated children and subjects older than 5 years of age living in the same household was associated with shedding of PV2 by a household contact. All models were adjusted by sex, age, IPV vaccination and OPV shedding by the same individual during the previous month of sample collection. CONCLUSION: Our results provide important evidence regarding the circulation of poliovirus in a mixed vaccination context (IPV+OPV) which mimics the "transitional phase" that occurs when countries use both vaccines simultaneously. Shedding of OPV2 by household contacts was most likely the source of infection of non-vaccinated children and subjects older than 5 years of age living in the same household.
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Heces/virología , Modelos Biológicos , Poliomielitis , Poliovirus , Vacunación , Esparcimiento de Virus , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , México/epidemiología , Poliomielitis/epidemiología , Poliomielitis/prevención & control , Poliomielitis/transmisiónRESUMEN
Oral poliovirus vaccine can mutate to regain neurovirulence. To date, evaluation of these mutations has been performed primarily on culture-enriched isolates by using conventional Sanger sequencing. We therefore developed a culture-independent, deep-sequencing method targeting the 5' untranslated region (UTR) and P1 genomic region to characterize vaccine-related poliovirus variants. Error analysis of the deep-sequencing method demonstrated reliable detection of poliovirus mutations at levels of <1%, depending on read depth. Sequencing of viral nucleic acids from the stool of vaccinated, asymptomatic children and their close contacts collected during a prospective cohort study in Veracruz, Mexico, revealed no vaccine-derived polioviruses. This was expected given that the longest duration between sequenced sample collection and the end of the most recent national immunization week was 66 days. However, we identified many low-level variants (<5%) distributed across the 5' UTR and P1 genomic region in all three Sabin serotypes, as well as vaccine-related viruses with multiple canonical mutations associated with phenotypic reversion present at high levels (>90%). These results suggest that monitoring emerging vaccine-related poliovirus variants by deep sequencing may aid in the poliovirus endgame and efforts to ensure global polio eradication.
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Secuenciación de Nucleótidos de Alto Rendimiento , Mutación , Vacuna Antipolio Oral/administración & dosificación , Poliovirus/clasificación , Poliovirus/aislamiento & purificación , Preescolar , Heces/virología , Femenino , Variación Genética , Humanos , Lactante , Masculino , México , Poliovirus/genética , Estudios ProspectivosRESUMEN
Community circulation of oral poliovirus vaccine (OPV) likely begins with household transmission. We analyzed stool collected from Zimbabwean mothers who were infected with human immunodeficiency virus (HIV) and those who were uninfected with HIV 1 to 24 weeks after infant oral poliovirus vaccination. Overall, only 5% of the mothers had detectable OPV (16 of 304) despite high infant shedding rates. OPV shedding was similar between HIV-infected mothers and those who were uninfected (11 [6.4%] of 171 vs 5 [3.8%] of 133, respectively) and between mothers of HIV-infected infants and those of uninfected infants (2 [3.5%] of 57 vs 9 [6.3%] of 144, respectively). Mothers of vaccinated infants are unlikely to shed OPV, even when they are infected with HIV.
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Países en Desarrollo , Infecciones por VIH/transmisión , Infecciones por VIH/virología , Transmisión Vertical de Enfermedad Infecciosa , Madres , Vacuna Antipolio Oral , Esparcimiento de Virus , Adulto , Fármacos Anti-VIH/uso terapéutico , Cesárea , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Embarazo , Carga Viral , ZimbabweRESUMEN
BACKGROUND: Prognosis for patients infected with human immunodeficiency virus (HIV) correlates with levels of CD4+ T cells. Initiation of antiretroviral therapy (ART) interrupts multiple points in the virus life cycle, causing an increase in CD4 cells. The rate at which the CD4 count recovers is highly variable and subject to influence by many factors. METHODS: We performed a deidentified data review to determine factors influencing the rate of CD4 count recovery after ART initiation. The associations between the changes in CD4 count from baseline at 5 time points, and factors including age, race, weight, baseline CD4 count, baseline viral load, specific ART medications and various comorbidities, were evaluated with univariate and multivariate analyses, using t-test, analysis of variance and multiple regressions. RESULTS: CD4 count continued to rise even up to 10 years after ART initiation, with the steepest increase in the first 3 months. High baseline viral load and low baseline CD4 count had the most consistent positive influence on CD4 count recovery rate across the 5 measured time points. Other factors that were significantly positively associated with CD4 recovery rate included younger baseline age, higher baseline weight and female gender. CONCLUSIONS: CD4 counts in HIV positive patients who consistently take ART continue to increase out to at least 10 years. Patients with a more advanced HIV infection at baseline, as indicated by high viral loads or low CD4 counts, have a greater rate of CD4 count recovery after starting ART, possibly because their CD4 counts have more room for improvement.
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Antirretrovirales/uso terapéutico , Linfocitos T CD4-Positivos/citología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Adulto , Antirretrovirales/administración & dosificación , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/inmunología , Registros Electrónicos de Salud , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/virología , Humanos , Masculino , Carga ViralRESUMEN
INTRODUCTION: Human T-lymphotropic virus type 1 or 2 (HTLV-1/2) co-infection in patients infected with the human immunodeficiency virus (HIV) can lead to increased morbidity. Because HTLV-1/2 shares a similar transmission route with HIV, HTLV-1/2 infection may be more prevalent in HIV-infected individuals. However, rates of HTLV-1/2 co-infection among HIV-infected individuals have not been studied recently in the United States. MATERIALS AND METHODS: We conducted a cross-sectional study using serum from 292 HIV-infected subjects from one clinic in Virginia. Serum samples were tested for co-infection with HTLV-1/2 by commercial ELISA; positive results were then confirmed via western blot, which also differentiated between HTLV-1 and -2. RESULTS: Seven (2.4%) of the subjects were co-infected with HTLV-2. One subject (among the seven co-infected with HTLV-2) was co-infected with HTLV-1 (0.3%). The only demographic factor significantly associated with HTLV-2 infection was history of intravenous drug abuse (p=0.002). CONCLUSIONS: While our results are limited to a single city, our low rates of co-infection do not support routine screening for HTLV-1/2 co-infection among HIV-infected individuals in the United States.
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Coinfección/sangre , Infecciones por VIH/virología , Infecciones por HTLV-I/virología , Infecciones por HTLV-II/virología , Coinfección/epidemiología , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/epidemiología , Infecciones por HTLV-II/complicaciones , Infecciones por HTLV-II/epidemiología , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Virus Linfotrópico T Tipo 2 Humano/aislamiento & purificación , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: A retrospective cross-sectional study was performed to assess the prevalence of elevated alkaline phosphatase (ALP) in patients infected with human immunodeficiency virus (HIV) and to determine the relation between ALP and specific antiretroviral therapy (ART). METHODS: A total of 2990 patients were included in this study. Data were collected from a major academic institution's HIV clinic using the most recent searchable values from patients' medical records. Included patients were 18 to 89 years old, had HIV, and their ALP results were available. Elevated ALP was defined as ALP >120 IU/L. Logistic regression analyses were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for predictors of elevated ALP level. RESULTS: In our total population of 2990, 15.4% (n = 459) had elevated ALP. In the bivariate analyses, older age (≥60 years; OR 4.1, 95% CI 2.6-6.4), female sex (OR 1.6, 95% CI 1.3-1.9), Other race (not African American) vs white (OR 1.9, 95% CI 1.8-3.3), elevated creatinine (OR 2.9, 95% CI 2.1-4.1), laboratory evidence of liver disease (OR 2.1, 95% CI 1.7-2.6), CD4 count <200 cells per cubic millimeter (OR 2.5, 95% CI 2.0-3.2), hepatitis C infection (OR 1.9, 95% CI 1.4-2.5), laboratory markers of bone turnover (OR 1.9, 95% CI 1.2-3.1), and non-nucleoside reverse-transcriptase inhibitors use (OR 1.2, 95% CI 1.02-1.15) were significantly associated with elevated ALP. Only the association with laboratory markers of bone turnover remained significant in the multivariate analysis, however. CONCLUSIONS: The results suggest that comorbidities and demographic variables have stronger associations with elevated ALP than specific antiretroviral therapy. Future research should be conducted to define the clinical significance of elevated ALP among patients infected with HIV.
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Fosfatasa Alcalina/sangre , Infecciones por VIH/enzimología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Estudios Transversales , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
INTRODUCTION: Pneumococcal infection is a leading cause of illness and death in HIV-infected adults. Current United States guidelines for HIV-infected adults recommend a single dose of the 13-valent pneumococcal conjugate vaccine (PCV-13) at any CD4 count and at least 1 y after receipt of the 23-valent pneumococcal polysaccharide vaccine (PPV). PPV is known to lead to hyporesponsiveness to subsequent pneumococcal vaccines for at least 1 y Whether PCV-13 would be more immunogenic if administered later after PPV receipt or at higher CD4 counts has not been tested. METHODS: We prospectively collected serum from 96 HIV-infected adults before and after PCV-13 receipt, and measured antibody concentrations against 4 pneumococcal serotypes (3, 6A, 7F, and 19A) via indirect ELISA according to the WHO protocol. Post-booster antibody concentrations and fold-rise in antibody concentrations were compared according to time from PPV receipt and baseline CD4 count using univariate and multivariate analyses. RESULTS: PPV receipt >3 versus 1-3 y prior did not significantly change post-vaccination antibody concentrations, but was associated with slightly higher fold-rise in antibody concentration for the 3 tested serotypes included in PPV, though this only reached significance for serotype 7F. CD4 count was significantly associated with post-vaccination antibody concentrations for 3 of 4 serotypes, but not for fold-rise in antibody concentration for any serotype. CONCLUSION: Waiting longer than 1 y after PPV receipt to administer PCV-13 may slightly improve the antibody response to serotypes included in both vaccines. While higher CD4 count at PCV-13 administration results in higher post-vaccination antibody concentrations, this is likely because higher CD4 count is also associated with higher pre-vaccination antibody concentrations.
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Formación de Anticuerpos , Recuento de Linfocito CD4 , Infecciones por VIH/inmunología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/inmunología , Adulto , Anciano , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Estados Unidos , Adulto JovenRESUMEN
INTRODUCTION: Uncontrolled HIV infection is known to activate the complement system, leading to an increase in chronic inflammation. Whether or not this activation of complement persists and contributes to chronic inflammation in subjects with HIV infection that is well controlled through use of antiretroviral therapy has not been studied. METHODS: We conducted an observational, cross-sectional study using sera from 305 adults with well-controlled HIV infection and 30 healthy controls. Sera was tested for markers of complement activation (C3a and C5a levels), complement function (CH50 assay), and immunoglobulin levels (IgG1-IgG4) as IgG can activate complement. We evaluated the association of well-controlled HIV infection with C3a, C5a, CH50, IgG1-IgG4, and total IgG levels using both univariate and multivariate analyses, controlling for factors such as age, sex, race, comorbidities (including hepatitis C coinfection), smoking status, and statin use. RESULTS: Well-controlled HIV infection was associated with a 54% increase in complement activation as measured by C3a levels compared with healthy controls (P < 0.0001). Hepatitis C coinfection was associated with a further 52% increase in complement activation, as measured by C3a levels, over HIV alone (P = 0.003). CONCLUSION: These results suggest that complement activation may contribute to a proinflammatory state even in well-controlled HIV infection. Furthermore, hepatitis C virus coinfection may be even more proinflammatory, in complement activation, compared with HIV infection alone.
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Activación de Complemento , Proteínas del Sistema Complemento/fisiología , Infecciones por VIH/fisiopatología , Adulto , Estudios de Casos y Controles , Proteínas del Sistema Complemento/metabolismo , Estudios Transversales , Femenino , Infecciones por VIH/sangre , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana EdadRESUMEN
Pertussis is a resurgent infection that can cause significant morbidity among adults. CD4 T cells are necessary for its clearance, but pertussis studies in HIV-infected adults are limited to case reports. We analyzed stored serum samples from 299 HIV-infected adults to determine the seroprevalence of pertussis among this population. We found that 4.3% of subjects had serologic evidence of recent pertussis infection, and annual incidence of pertussis infection among subjects not vaccinated against pertussis in the last 5 years was 10.5%-17.5%. Prospective studies are needed to define the clinical presentation of pertussis in HIV-infected adults and to optimize vaccination strategies.
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Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Bordetella pertussis/inmunología , Infecciones por VIH/epidemiología , Tos Ferina/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Adulto , Anticuerpos Antibacterianos/análisis , Anticuerpos Antibacterianos/inmunología , Recuento de Linfocito CD4 , Estudios Transversales , Infecciones por VIH/inmunología , Infecciones por VIH/microbiología , Humanos , Prevalencia , Estudios Seroepidemiológicos , Estados Unidos/epidemiología , Tos Ferina/inmunología , Tos Ferina/microbiologíaRESUMEN
BACKGROUND: Inactivated polio vaccine (IPV) is necessary for global polio eradication because oral polio vaccine can rarely cause poliomyelitis as it mutates and may fail to provide adequate immunity in immunocompromised populations. However, IPV is unaffordable for many developing countries. Intradermal IPV shows promise as a means to decrease the effective dose and cost of IPV, but prior studies, all using 20% of the standard dose used in intramuscular IPV, resulted in inferior antibody titers. METHODS: We randomly assigned 231 adults with well-controlled human immunodeficiency virus infection at a ratio of 2:2:2:1 to receive 40% of the standard dose of IPV intradermally, 20% of the standard dose intradermally, the full standard dose intramuscularly, or 40% of the standard dose intramuscularly. Intradermal vaccination was done using the NanoPass MicronJet600 microneedle device. RESULTS: Baseline immunity was 87%, 90%, and 66% against poliovirus serotypes 1, 2, and 3, respectively. After vaccination, antibody titers increased a median of 64-fold. Vaccine response to 40% of the standard dose administered intradermally was comparable to that of the standard dose of IPV administered intramuscularly and resulted in higher (although not significantly) antibody titers. Intradermal administration had higher a incidence of local side effects (redness and itching) but a similar incidence of systemic side effects and was preferred by study participants over intramuscular administration. CONCLUSIONS: A 60% reduction in the standard IPV dose without reduction in antibody titers is possible through intradermal administration.
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Infecciones por VIH/inmunología , Inmunización Secundaria/métodos , Poliomielitis/inmunología , Poliomielitis/prevención & control , Vacuna Antipolio de Virus Inactivados/inmunología , Adulto , Anticuerpos Antivirales/sangre , Femenino , Humanos , Inyecciones Intradérmicas , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Resultado del Tratamiento , Adulto JovenRESUMEN
Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial vaccine doses induced antibodies at titers comparable to those after immunization with full human dose delivered intramuscularly. The results suggest that intradermal delivery of IPV may lead to dose-sparing effect and reduction of the vaccination cost.
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Vacuna Antipolio de Virus Inactivados/inmunología , Animales , Anticuerpos Antivirales/sangre , Relación Dosis-Respuesta Inmunológica , Femenino , Inyecciones Intradérmicas/instrumentación , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Vacuna Antipolio de Virus Inactivados/economía , Ratas , Ratas WistarAsunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Accesibilidad a los Servicios de Salud , Aceptación de la Atención de Salud , Diagnóstico Precoz , Femenino , Infecciones por VIH/diagnóstico , Conocimientos, Actitudes y Práctica en Salud , Humanos , Lactante , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Aceptación de la Atención de Salud/psicología , Estigma Social , Apoyo SocialRESUMEN
OBJECTIVES: Hypoglycorrhachia, a low glucose level in the cerebrospinal fluid (CSF), can suggest bacterial, fungal or tuberculous meningitis. When tests for these common infectious etiologies are negative, many clinicians are unsure of which diagnoses to consider, resulting in delayed treatment. The authors analyzed the diagnoses associated with hypoglycorrhachia to determine their relative frequencies at our institution and summarized all the diagnoses associated with hypoglycorrhachia in the literature. METHODS: Retrospective analysis of adults with hypoglycorrhachia at a tertiary care teaching hospital over a 5-year period. Inclusion criteria included CSF glucose <40 mg/dL and age 18 years or older. Exclusion criteria included CSF/serum glucose ≥0.6. RESULTS: Eighty-nine unique hypoglycorrhachia episodes were identified. The most common etiologies among all episodes of hypoglycorrhachia were bacterial meningitis (24%), fungal meningitis (15%), stroke/bleed (13%), malignancy (11%), viral meningitis (6%), neurosarcoidosis (4%), neurosyphilis (4%) and cerebral toxoplasmosis (3%). The most common etiology was fungal meningitis (38%) among HIV-infected patients and bacterial meningitis (62%) among neurosurgery patients. However, in patients without HIV or neurosurgical history, noninfectious etiologies (stroke/bleed, 24%; malignancy, 22%) were most common. CONCLUSIONS: Many diagnoses, both infectious and noninfectious, lead to hypoglycorrhachia and must be considered in the differential diagnosis.