PubMed Health⌕ Search

Biomedical subjects

Myron J Levin

Publications and source records attributed to Myron J Levin.

At least 19 recordsLinked to original sources

Safety and Immunogenicity of Varicella Vaccination in Children and Adolescents Living With HIV: A Systematic Review.

INTRODUCTION: Preventing varicella-zoster virus infection is important in the management of human immunodeficiency virus (HIV)-positive persons. Varicella remains endemic worldwide, and HIV-positive persons can experience greater morbidity than the general population. We summarized the global literature on the safety and immunogenicity of the varicella vaccine in HIV-positive children. METHODS: Systematic review of original reports on varicella vaccination of HIV-positive children, published through December 31, 2024, including assessment of safety, immunologic responses and effectiveness after vaccination. RESULTS: Eighteen articles were analyzed. Local reactions were the most common adverse events, albeit infrequent (<21% and <10% of vaccinees after dose 1 and 2, respectively). Systemic reactions were also infrequent, consisting mostly of low-grade fever. A vaccine-related rash, reported in <5% of vaccinees, had fewer lesions and a shorter duration than typical varicella. Serious adverse events were reported only when the vaccine was inadvertently administered to children with severe HIV immunosuppression. Varicella vaccination had no clinically significant impact on plasma HIV RNA or CD4+ T-cell count after either dose. An antibody response was reported in 60%-79% of HIV-positive vaccinees after dose 2 and often declined more rapidly than in uninfected children. Cell-mediated immunity was detected in 67%-83% after dose 2. No significant differences in adverse events or short-term immune response after vaccination correlated with past or current CD4+ T-cell status. CONCLUSIONS: The varicella vaccine had a favorable safety profile and induced specific immune responses in most nonseverely immunocompromised HIV-positive children. The vaccine remains contraindicated for persons with severe HIV infection. Robust data on the durability of immune response and long-term effectiveness are needed.

Humans↗

DNA sequence variability in isolates recovered from patients with postvaccination rash or herpes zoster caused by Oka varicella vaccine.

Little is known about the pathogenic potential of individual strains in the varicella vaccine. We analyzed genomic variation among specimens obtained from vaccine recipients with postvaccination rash or herpes zoster (HZ), focusing on polymorphisms between live attenuated varicella vaccine virus and wild-type varicella-zoster virus. Eleven of 18 postvaccination HZ specimens contained >1 strain, and 7 of 18 appeared to be clonal. All 21 postvaccination rash specimens contained mixtures of vaccine strains. Four single-nucleotide polymorphisms (SNPs) consistently occurred in every isolate; all were polymorphisms in open-reading frame (ORF) 62, and 2 confer amino acid substitutions in the immediate-early protein 62. Four wild-type SNPs occurred in every isolate: one each occurred in ORF 10, ORF 21, ORF 62, and a noncoding region upstream of ORF 64. The frequencies of the remaining wild-type SNPs were variable, with the SNPs uniformly expressed (even in mixtures) in 20.5%-97.4% of isolates (mean frequency, 67.7%). No 2 clinical isolates had identical SNP profiles; as such, vaccine latency usually involves >1 strain.

Adolescent↗

Recommendations for the management of herpes zoster.

The objective of this article is to provide evidence-based recommendations for the management of patients with herpes zoster (HZ) that take into account clinical efficacy, adverse effects, impact on quality of life, and costs of treatment. Systematic literature reviews, published randomized clinical trials, existing guidelines, and the authors' clinical and research experience relevant to the management of patients with HZ were reviewed at a consensus meeting. The results of controlled trials and the clinical experience of the authors support the use of acyclovir, brivudin (where available), famciclovir, and valacyclovir as first-line antiviral therapy for the treatment of patients with HZ. Specific recommendations for the use of these medications are provided. In addition, suggestions are made for treatments that, when used in combination with antiviral therapy, may further reduce pain and other complications of HZ.

2-Aminopurine↗

Factors that affect in vitro measurement of the susceptibility of herpes simplex virus to nucleoside analogues.

OBJECTIVES: To identify factors that contribute to variability of HSV antiviral susceptibility breakpoints. METHODS: Acyclovir and penciclovir IC(50)'s for 12 HSV clinical isolates were measured in two laboratories using plaque reduction assay (PRA), an enzyme immunoassay (EIA)-based antigen reduction, and DNA hybridization on Vero, A549, MRC-5, HEL299 and HELG monolayers. Pair-wise comparisons were performed to evaluate variables including testing laboratory, technique, monolayer, and antiviral. The proportion of false results was analyzed using a conventional susceptibility IC(50) breakpoint of 2 microg/ml. RESULTS: Acyclovir-resistant HSV isolates were correctly identified by all methods. In contrast, there were 6-67% of susceptible isolates incorrectly characterized as drug-resistant. Variables associated with these errors included testing site, assay method, cell line and antiviral. A549, DNA hybridization, and penciclovir were associated with the highest IC(50)'s, whereas the PRA, EIA, and human fibroblast-monolayers provided the best differentiation between susceptible and resistant HSV isolates. CONCLUSIONS: The current recommendations to use a single discriminating value to define HSV resistance to nucleoside analogues can be problematic. False results are influenced in various degrees by the laboratory method, tissue culture and antivirals.

Acyclovir↗

Administration of live varicella vaccine to HIV-infected children with current or past significant depression of CD4(+) T cells.

BACKGROUND: Varicella can be a severe illness in human immunodeficiency virus (HIV)-infected children. The licensed, live attenuated varicella vaccine is safe and immunogenic in HIV-infected children with minimal symptoms and good preservation of CD4(+) T cells (Centers for Disease Control and Prevention immunologic category 1). METHODS: To study the safety and immunogenicity of this vaccine in varicella-zoster virus (VZV)-naive, HIV-infected children with moderate symptoms and/or more pronounced past or current decreases in CD4(+) T cell counts, such children (age, 1-8 years) received 2 doses of vaccine 3 months apart. The children were observed in a structured fashion for adverse events. Blood was tested for VZV antibody and VZV-specific cell-mediated immunity (CMI) at baseline, 8 weeks after each dose, and annually for 3 years. Subjects who had no evidence of immunity 1 year after vaccination received a third dose and were retested. RESULTS: The vaccine was well tolerated; there were no vaccine-related, serious adverse events. Regardless of immunologic category, at least 79% of HIV-infected vaccine recipients developed VZV-specific antibody and/or CMI 2 months after 2 doses of vaccine, and 83% were responders 1 year after vaccination. CONCLUSIONS: HIV-infected children with a CD4(+) T cell percentage of > or =15% and a CD4(+) T cell count of > or =200 cells/ microL are likely to benefit from receiving varicella vaccine.

Anti-HIV Agents↗

Cytomegalovirus-specific cell-mediated immunity in HIV-infected children on HAART.

The objectives of this study were to define the magnitude, time course, and virologic and immunologic correlates of HAART-associated reconstitution of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) in pediatric HAART recipients. Thirty-five HIV-infected CMV-seropositive subjects < or = 22 years on or about to receive HAART had CMV-CMI measured by responder cell frequency (RCF) and interferon-gamma (IFN-gamma) secretion over 3 years. RCF was detected in 33, 52, 38, and 28% before HAART and at years 1, 2, and > or = 3, respectively. Corresponding percentages for IFN-gamma were 100, 85, 100, and 38%. Neither RCF nor IFN-gamma was significantly associated with CD4% before or after HAART initiation. Lower HIV replication was associated with a higher proportion of subjects with positive RCF, but not IFN-gamma. There were no clinical CMV manifestations during the study. HIV-infected children did not demonstrate a significant increase in CMV-CMI with longer HAART duration, which suggests that CMV immunereconstitution involves more complex immunologic and virologic interactions than previously anticipated.

Adolescent↗

Validation of a 3-factor scoring model for the Pittsburgh sleep quality index in older adults.

STUDY OBJECTIVES: The Pittsburgh Sleep Quality Index (PSQI) is widely used to assess subjective sleep disturbances in psychiatric, medical, and healthy adult and older adult populations. Yet, validation of the PSQI single-factor scoring has not been carried out. DESIGN: The PSQI was administered as a self-report questionnaire. Using a cross-validation approach, scores from the PSQI were analyzed with exploratory and confirmatory factor analyses. SETTING: San Diego, Denver, and Los Angeles community-based clinics. PARTICIPANTS: Community-dwelling depressed and nondepressed adults older that 60 years of age (N = 417) MEASUREMENTS AND RESULTS: Results yielded a 3-factor scoring model that obtained a measure of perfect fit and was significantly better fitted than either the original single-factor model or a 2-factor model. Components of the 3 factors were characterized by the descriptors sleep efficiency, perceived sleep quality, and daily disturbances. CONCLUSIONS: These findings validate the factor structure of the PSQI and demonstrate that a 3-factor score should be used to assess disturbances in three separate factors of subjective sleep reports.

Aged↗

Immunogenicity, safety, and predictors of response after a pneumococcal conjugate and pneumococcal polysaccharide vaccine series in human immunodeficiency virus-infected children receiving highly active antiretroviral therapy.

BACKGROUND: The immunogenicity and safety of 2 doses of pneumococcal conjugate vaccine (PCV) and 1 dose of pneumococcal polysaccharide vaccine (PPV) were evaluated in human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART). METHODS: Children 2 to <19 years, receiving stable HAART for > or =3-6 months, with HIV RNA PCR <30,000-60,000 copies/mL, received 2 doses of PCV and 1 dose of PPV at sequential 8-week intervals. Antibodies to pneumococcal serotypes (STs) 1 (PPV only) and 6B, 14, 19F, and 23F (PCV and PPV) were measured by ELISA. RESULTS: Two hundred sixty-three subjects were enrolled, of whom 225 met criteria for inclusion in the primary dataset. Antibody concentrations were low at entry, despite previous PPV in 75%. After vaccination, 76%-96% had concentrations > or =0.5 microg/mL and 62-88% > or =1.0 microg/mL to the 5 STs (geometric mean concentrations [GMCs] = 1.44-4.25 microg/mL). Incremental gains in antibody concentration occurred with each vaccine dose. Predictors of response included higher antibody concentration at entry, higher immune stratum (based on nadir CD4% before HAART and CD4% at screening), lower entry viral RNA, longer duration of the entry HAART regimen, and age <7 years. Response was more consistently related to screening CD4% than nadir CD4%. Seven percent had vaccine-related grade 3 events, most of which were local reactions. CONCLUSIONS: Two PCVs and 1 PPV were immunogenic and safe in HIV-infected children 2 to <19 years who were receiving HAART. Responses were suggestive of functional immune reconstitution. Immunologic status based on nadir and, especially, current CD4% and control of HIV viremia were independent determinants of response.

Adolescent↗

Impairments in health functioning and sleep quality in older adults with a history of depression.

OBJECTIVES: To determine whether older adults with a history of depression show impairments in health functioning and sleep quality at a gradient between older adults with no history of depression and those with current major depression and to examine whether poor sleep quality contributes to declines in health functioning in addition to the contribution of depressive symptoms. DESIGN: Cross-sectional. SETTING: Three urban communities: Denver, Colorado, and Los Angeles and San Diego, California. PARTICIPANTS: Two hundred community-dwelling adults aged 60 and older who were never mentally ill, 143 with a history of major or minor depressive disorder in remission, and 67 with a current depressive disorder. MEASUREMENTS: Diagnosis, Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; health functioning (Medical Outcomes Study 36-item Short-Form Health Survey); depressive symptom severity (Beck Depression Inventory); and sleep quality (Pittsburgh Sleep Quality Index). RESULTS: Older adults with a history of depression showed impairments in sleep quality and had lower levels of health functioning than controls; these impairments were at a gradient with declines in those with current depression. Poor sleep quality was independently associated with declines in health perception in older adults with and without depression. CONCLUSION: These findings have important health implications for older people who have a lifetime history of depression, given evidence that poor health functioning is a risk factor for depression recurrence as well as mortality. Moreover, in view of the association between sleep quality and health status, testing of interventions that target sleep quality might identify strategies to improve health functioning in older adults.

Aged↗

Postentry events are responsible for restriction of productive varicella-zoster virus infection in Chinese hamster ovary cells.

Productive infection of varicella-zoster virus (VZV) in vitro is restricted almost exclusively to cells derived from humans and other primates. We demonstrate that the restriction of productive VZV infection in CHO-K1 cells occurs downstream of virus entry. Entry of VZV into CHO-K1 cells was characterized by utilizing an ICP4/beta-galactosidase reporter gene that has been used previously to study herpes simplex virus type 1 entry. Entry of VZV into CHO-K1 cells involved cell surface interactions with heparan sulfate glycosaminoglycans and a cation-independent mannose-6-phosphate receptor. Lysosomotropic agents inhibited the entry of VZV into CHO-K1 cells, consistent with a low-pH-dependent endocytic mechanism of entry. Infection of CHO-K1 cells by VZV resulted in the production of both immediate early and late gene products, indicating that a block to progeny virus production occurs after the initiation of virus gene expression.

Animals↗

Clinical and in vitro evaluation of cidofovir for treatment of adenovirus infection in pediatric hematopoietic stem cell transplant recipients.

Post-hematopoietic stem cell transplantation (HSCT) adenovirus infections were identified in 31 of 204 consecutive pediatric HSCT patients, 18 of whom had severe manifestations of infection. Cidofovir treatment led to clinical improvement in 8 of 10 patients with severe infection and to virologic clearance in 9 patients. In vitro susceptibility to cidofovir was demonstrated in 12 clinical adenovirus isolates. Cidofovir is a promising treatment option for this population.

Adenoviridae↗

Nectin-1/HveC Mediates herpes simplex virus type 1 entry into primary human sensory neurons and fibroblasts.

Immunocytochemistry detects nectin-1/HveC, nectin-2/HveB, and HVEM/HveA on the surface of sensory neurons and fibroblasts grown as primary cultures from human dorsal root ganglia. Viral entry into these cultured cells was assayed by infection with a recombinant herpes simplex virus type 1 (HSV-1) expressing green fluorescent protein. Soluble, truncated nectin-1 polypeptide, as well as polyclonal and monoclonal antibodies against nectin-1, inhibited infection of neurons, whereas polypeptides and antibodies capable of inhibiting HSV-1 interaction with nectin-2 and herpesvirs entry mediator (HVEM) failed to prevent infection of neuronal cells. These results demonstrate that nectin-1 is the primary receptor for HSV-1 entry into human fetal neurons. Viral entry into fibroblasts was also reduced by soluble nectin-1 but not by soluble HVEM. However, in contrast to the results obtained with neurons, antibodies against receptors failed to inhibit entry into fibroblasts, indicating that unlike neurons, fibroblasts have multiple receptors or mechanisms for HSV-1 entry.

Cell Adhesion Molecules↗

Responder cell frequency estimation and binomial three-level nonlinear mixed effects model in limiting dilution assays.

Responder cell frequencies (RCF), which describe vaccine-boosted immune responses in herpes zoster (HZ) prevention studies, have been estimated by using limiting dilution assays (LDA). The theoretical linearity assumption between the logarithm of the proportion of nonresponding wells (s) and the cell concentration (N) (or dilution level) in LDA, based on the single-hit Poisson model, is often violated with observed data resulting in biased estimates of RCF. In this article, the Poisson assumption is modified by applying a mixture of Poisson and gamma distributions, resulting in a negative binomial assumption, which presents a better fit between s and N. In LDA for HZ prevention studies, binary responses (responder or non-responder wells) are measured repeatedly at different cell concentrations and over time. To account for the correlation between responses to varying dilution levels from individuals, and the correlation between repeated assays of individuals over time simultaneously, a binomial three-level nonlinear mixed-effects model is proposed. For parameter estimation, a maximum likelihood method is applied via adaptive Gaussian quadrature. There is a lack of non-Gaussian multilevel nonlinear mixed-effects software, which can execute such a complicated fit. In this article, an algorithm for the three-level nonlinear mixed-effects model, which can be inserted into the code in the SAS procedure NLMIXED, is suggested.

Cell Count↗

GB virus C infection in children with perinatal human immunodeficiency virus infection.

BACKGROUND: GB virus C (GBV-C) infection occurs in 20-40% of human immunodeficiency virus (HIV)-infected adults, and coinfection is associated with improved HIV disease outcome. METHODS: To determine the prevalence of GBV-C infection in children who were perinatally infected with HIV, we conducted a cross-sectional prevalence survey in a cohort of perinatally infected HIV-positive children selected from a large, multicenter observational protocol. A blood specimen was obtained and tested for GBV-C viremia with the use of a qualitative GBV-C RNA assay and screened for past GBV-C infection with enzyme-linked immunosorbent assay to detect antibodies to the GBV-C envelope protein E2 (E2 Ab). RESULTS: The 354 children who participated in the substudy were relatively healthy, with a median CD4 of 784 cells/mm and median HIV-1 viral load of 1055 copies/mL. The prevalence of GBV-C viremia was 20 of 353 or 5.7% (95% confidence interval, 3.5-8.6%), and the prevalence of E2 Ab was 12 of 354 or 3.4% (95% confidence interval, 1.8-5.8%). GBV-C viremic patients were older than patients without past GBV-C infection (median age, 12.8 years versus 10.7 years). Median CD4 lymphocyte counts were highest in subjects without GBV-C infection and lowest in those with E2 Ab. CONCLUSIONS: GBV-C prevalence rates are lower in children with perinatal HIV infection than those reported for HIV-infected adults. With the exception of evidence that GBV-C viremic children had lower rates of Centers for Disease Control and Prevention HIV disease category C disease before GBV-C testing, we did not find evidence of improved HIV disease outcome in coinfected patients, but the number of HIV/GBV-C-coinfected children was small.

AIDS-Related Opportunistic Infections↗

Varicella-zoster virus activates inflammatory cytokines in human monocytes and macrophages via Toll-like receptor 2.

The pattern recognition receptor Toll-like receptor 2 (TLR2) has been implicated in the response to several human viruses, including herpes simplex viruses (types 1 and 2) and cytomegalovirus. We demonstrated that varicella-zoster virus (VZV) activates inflammatory cytokine responses via TLR2. VZV specifically induced interleukin-6 (IL-6) in human monocytes via TLR2-dependent activation of NF-kappaB, and small interfering RNA designed to suppress TLR2 mRNA reduced the IL-6 response to VZV in human monocyte-derived macrophages. Unlike other herpesviruses, the cytokine response to VZV was species specific. VZV did not induce cytokines in murine embryonic fibroblasts or in a mouse cell line, although VZV did activate NF-kappaB in a human cell line expressing a murine TLR2 construct. Together, these results suggest that TLR2 may play a role in the inflammatory response to VZV infection.

Animals↗

Resistance of herpes simplex virus infections to nucleoside analogues in HIV-infected patients.

Antiviral treatment of herpes simplex virus (HSV) infections with nucleoside analogues has been well established for >2 decades, but isolation of drug-resistant HSV from immunocompetent patients has remained infrequent (0.1%-0.7% of isolates) during this period. Even when drug-resistant HSV is isolated from an immunocompetent patient, this virus, with rare exceptions, is cleared normally without adverse clinical outcome. Although drug-resistant HSV is more commonly isolated from immunocompromised patients (4%-7% of isolates) and is more likely to be clinically significant, the prevalence of drug-resistant HSV even among these patients, has been stable over the past 2 decades. Despite this stable prevalence, disease due to drug-resistant HSV remains an important problem for many immunocompromised patients, including those with HIV infection. This article reviews the prevalence, pathogenesis, and implications of drug-resistant HSV infections in HIV-infected patients.

Acyclovir↗

Varicella-Zoster virus-specific cell-mediated immunity in HIV-infected children receiving highly active antiretroviral therapy.

Herpes zoster (HZ) is a frequent complication of advanced human immunodeficiency virus (HIV) infection. We determined the effect of highly active antiretroviral therapy (HAART) on reconstitution of varicella-zoster virus (VZV)-specific cell-mediated immunity (VZV-CMI) in 56 VZV- and HIV-infected children. VZV-CMI did not change over the course of >/=3 years of observation, despite a reduction in HIV load. VZV-CMI correlated with lower HIV load but not with CD4 cell percentage. The incidence of HZ was unaffected by HAART. None of 5 patients who developed HZ during the study had VZV-CMI before developing HZ. After developing HZ, only the 2 HAART-compliant patients developed VZV-CMI. Thus, VZV-specific immune reconstitution in HIV infection may require antigenic reexposure, in addition to control of HIV replication.

Adolescent↗

Hepatitis C prevalence in children with perinatal human immunodeficiency virus infection enrolled in a long-term follow-up protocol.

OBJECTIVE: To evaluate the prevalence of hepatitis C virus (HCV) infection in children with perinatal human immunodeficiency virus (HIV) infection. DESIGN: Cross-sectional substudy. SETTING: Multicenter study from 41 sites in the United States. PATIENTS: Children with perinatal HIV infection were randomly selected from a large, long-term, follow-up protocol. MAIN OUTCOME MEASURE: Hepatitis C infection was defined as having positive test results on both HCV antibody and HCV RNA assays. RESULTS: Five hundred thirty children enrolled in the substudy; definitive HCV test results were available for 525 children. Eighty-three percent were of a minority race or ethnicity. They were equally distributed by sex, had a median age of 10.7 years, and were relatively healthy, with 75% having CD4+ lymphocyte counts greater than 500 cells/mm3. Eight of 525 children (1.5%; 95% confidence interval [CI], 0.7%-3.0%) infected with HIV were coinfected with HCV. In contrast, the rate of HCV infection in a serosurvey of more than 2700 children aged 6 to 11 years from the National Health and Nutrition Examination Survey was 0.2% (95% CI, 0.04%-0.6%). In our study, there were no differences between children coinfected with HIV and HCV and those without HCV infection in terms of demographic characteristics, CD4+ or CD8+ T-lymphocyte counts, HIV 1 RNA levels, preterm or mode of delivery, or liver disease; however, the number of children coinfected with HIV and HCV was small. CONCLUSION: While HCV prevalence infection rates are low in children with perinatal HIV infection, they are 8 to 10 times higher than reported in HCV serosurveys of children in the United States.

Adolescent↗