Papers by Leslie Serchuck
The Journal of Allergy and Clinical Immunology, Apr 1, 2005
Early markers that predict immunologic long-term nonprogression in infants with perinatally acqui... more Early markers that predict immunologic long-term nonprogression in infants with perinatally acquired HIV infection might assist in subsequent antiretroviral treatment decisions. We sought to identify early markers of immunologic long-term HIV disease nonprogression. We analyzed immunologic and virologic characteristics at 1 and 2 months of age in HIV-infected children who were enrolled in the Women and Infants Transmission Study and born before 1995, comparing immunologic long-term nonprogressors (ILTNPs; n = 10) with non-ILTNPs (n = 127). ILTNPs were children who survived to 8 years or older with CD4 percentages of 25% or greater and counts of 500 cells/mm 3 or more without receiving highly active antiretroviral therapy. Non-ILTNPs were defined as all other HIV-infected children. Receiver operating characteristic curve analysis was used to assess combined sensitivity and specificity for each of these characteristics and to determine potential threshold values to discriminate between ILTNPs and non-ILTNPs. Characteristics in the first 2 months of life associated with ILTNP status in univariate analysis included higher CD4 percentages, lower CD8 + percentages, lower CD8 + HLA-DR + percentages, and lower HIV-1 RNA PCR values. In receiver operating characteristic analysis CD8 + HLA-DR + percentage had the best combined sensitivity and specificity for discriminating between ILTNPs and non-ILTNPs. CD8 + HLA-DR + percentages of 5% or less predicted ILTNP status with 80% sensitivity and 80% specificity. In multivariate analysis CD8 + HLA-DR+ percentage of 5% or less remained a significant predictor of ILTNP status after adjusting for CD3 + CD4 + percentage and HIV-1 RNA PCR value (odds ratio, 15.4; 95% CI, 1.9-124.7). CD8 + HLA-DR + T-lymphocyte percentage of less than 5% at 1 to 2 months of age might be predictive for ILTNP status but should not be used at this time to make treatment-deferral decisions. Immune activation in HIV-infected infants might herald more disease progression. Further study of the use of this subpopulation in early infancy to predict ILTNP status is warranted.
Clinical Infectious Diseases, Mar 15, 2005
Background. Despite previous study, it remains unclear whether hepatitis C virus (HCV) coinfectio... more Background. Despite previous study, it remains unclear whether hepatitis C virus (HCV) coinfection affects the progression of human immunodeficiency virus (HIV) type 1 infection. The Women and Infants Transmission Study provided an opportunity to assess this issue. Methods. Longitudinal data on 652 HIV-1-infected women enrolled in the study before the availability of highly active antiretroviral therapy (HAART; 1989-1995) were analyzed. Random effects models were used to determine whether HCV coinfection was associated with different CD4 + cell percentages and HIV-1 RNA levels over time, and Cox proportional hazards models were used to compare the rates of clinical progression to acquired immunodeficiency syndrome (AIDS) or death. Results. Of 652 women, 190 (29%) were HCV infected. During follow-up, 19% of women were exposed to HAART. After controlling for indicators of disease progression (CD4 + cell percentages and HIV-1 RNA levels determined closest to the time of delivery in pregnant women), ongoing drug use, receipt of antiretroviral therapy, and other important covariates, no differences were detected in the HIV-1 RNA levels, but the CD4 + cell percentages were slightly higher in HCV-infected women than in HCV-uninfected women. During follow-up, 48 women had progression to a first clinical AIDS-defining illness (ADI), and 26 died with no documented antecedent ADI. In multivariable analyses, HCV-infected participants did not have faster progression to a first class C AIDS-defining event or death (relative hazard, 0.75; 95% confidence interval, 0.37-1.53). Conclusions. In this cohort, the rate of clinical progression of HIV-1 infection was not greater for HCVinfected women. Hepatitis C virus (HCV) coinfection is common among HIV-infected persons, particularly among persons who acquired HIV parenterally through injection drug use
Cambridge University Press eBooks, May 4, 2006
Clinical Infectious Diseases, Feb 1, 2005
In 2001, CDC, the National Institutes of Health, and the Infectious Diseases Society of America c... more In 2001, CDC, the National Institutes of Health, and the Infectious Diseases Society of America convened a working group to develop guidelines for therapy of human immunodeficiency virus (HIV)-associated opportunistic infections to serve as a companion to the Guidelines for Prevention of Opportunistic Infections Among HIV-Infected Persons. In recognition of unique considerations related to HIV infection among infants, children, and adolescents, a separate pediatric working group was established. Because HIV-infected women coinfected with opportunistic pathogens might be more likely to transmit these infections to their infants than women without HIV infection, guidelines for treating opportunistic pathogens among children should consider treatment of congenitally acquired infections among both HIVexposed but uninfected children and those with HIV infection. In addition, the natural history of opportunistic infections among HIV-infected children might differ from that among adults. Compared with opportunistic infections among HIV-infected adults, which are often caused by reactivation of pathogens acquired before HIV infection when host immunity was intact, opportunistic infections among children often reflect primary acquisition of the pathogen and, among children with perinatal HIV infection, infection acquired after HIV infection has been established and begun to compromise an already immature immune system. Laboratory diagnosis of opportunistic infections can be more difficult with children. Finally, treatment recommendations should consider differences between adults and children in terms of drug pharmacokinetics, dosing, formulations, administration, and toxicities. This report focuses on treatment of opportunistic infections that are common in HIV-exposed and infected infants, children, and adolescents in the United States.
It is recognized that guidelines for antiretroviral use in pediatric patients are rapidly evolvin... more It is recognized that guidelines for antiretroviral use in pediatric patients are rapidly evolving. The Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children will review new data on an ongoing basis and provide regular updates to the guidelines, and the most recent information is available on the AIDSinfo Web site (http://AIDSinfo.nih.gov).
Human immunodeficiency virus (HIV)-infected children and adolescents who are failing antiretrovir... more Human immunodeficiency virus (HIV)-infected children and adolescents who are failing antiretrovirals may have a better virologic response when drug exposures are increased, using higher protease inhibitor doses or ritonavir boosting. We studied the pharmacokinetics and safety of high-dose lopinavir-ritonavir (LPV/r) in treatment-experienced patients, using an LPV/r dose of 400/100 mg/m 2 orally every 12 h (p.o. q12h) (without nonnucleoside reverse transcriptase inhibitor [NNRTI]), or 480/120 mg/m 2 p.o. q12h (with NNRTI). We calculated the LPV inhibitory quotient (IQ), and when the IQ was <15, saquinavir (SQV) 750 mg/m 2 p.o. q12h was added to the regimen. We studied 26 HIV-infected patients. The median age was 15 years (range, 7 to 17), with 11.5 prior antiretroviral medications, 197 CD4 cells/ml, viral load of 75,577 copies/ml, and a 133-fold change in LPV resistance. By treatment week 2, 14 patients had a viral-load decrease of >0.75 log 10 , with a median maximal decrease in viral load of ؊1.57 log 10 copies/ml at week 8. At week 2, 19 subjects showed a median LPV area under the concentration-time curve (AUC) of 157.2 (range, 62.8 to 305.5) g ⅐ h/ml and median LPV trough concentration (C trough) of 10.8 (range, 4.1 to 25.3) g/ml. In 16 subjects with SQV added, the SQV median AUC was 33.7 (range, 4.4 to 76.5) g ⅐ h/ml and the median SQV C trough was 2.1 (range, 0.2 to 4.1) g/ml. At week 24, 18 of 26 (69%) subjects remained in the study. Between weeks 24 and 48, one subject withdrew for nonadherence and nine withdrew for persistently high virus load. In antiretroviral-experienced children and adolescents with HIV, high doses of LPV/r with or without SQV offer safe options for salvage therapy, but the modest virologic response and the challenge of adherence to a regimen with a high pill burden may limit the usefulness of this approach.
MMWR Recommendations and Reports, Dec 3, 2004
In 2001, CDC, the National Institutes of Health, and the Infectious Diseases Society of America c... more In 2001, CDC, the National Institutes of Health, and the Infectious Diseases Society of America convened a working group to develop guidelines for therapy of human immunodeficiency virus (HIV)-associated opportunistic infections to serve as a companion to the Guidelines for Prevention of Opportunistic Infections Among HIV-Infected Persons. In recognition of unique considerations related to HIV infection among infants, children, and adolescents, a separate pediatric working group was established. Because HIV-infected women coinfected with opportunistic pathogens might be more likely to transmit these infections to their infants than women without HIV infection, guidelines for treating opportunistic pathogens among children should consider treatment of congentially acquired infections among both HIV-exposed but uninfected children and those with HIV infection. In addition, the natural history of opportunistic infections among HIV-infected children might differ from that among adults. ...
This article cites 27 articles, 9 of which can be accessed free at:
MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports, 2009
This report updates and combines into one document earlier versions of guidelines for preventing ... more This report updates and combines into one document earlier versions of guidelines for preventing and treating opportunistic infections (OIs) among HIV-exposed and HIV-infected children, last published in 2002 and 2004, respectively. These guidelines are intended for use by clinicians and other health-care workers providing medical care for HIV-exposed and HIV-infected children in the United States. The guidelines discuss opportunistic pathogens that occur in the United States and one that might be acquired during international travel (i.e., malaria). Topic areas covered for each OI include a brief description of the epidemiology, clinical presentation, and diagnosis of the OI in children; prevention of exposure; prevention of disease by chemoprophylaxis and/or vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; and dis...
ERJ Open Research
Little is known about the prevalence, clinical characteristics and impact of hypothyroidism in pa... more Little is known about the prevalence, clinical characteristics and impact of hypothyroidism in patients with sarcoidosis. We aimed to determine the prevalence and clinical features of hypothyroidism and its relation to organ involvement and other clinical manifestations in patients with sarcoidosis.We conducted a national registry-based study investigating 3835 respondents to the Sarcoidosis Advanced Registry for Cures Questionnaire between June 2014 and August 2019. This registry is based on a self-reported, web-based questionnaire that provides data related to demographics, diagnostics, sarcoidosis manifestations and treatment. We compared sarcoidosis patients with and without self-reported hypothyroidism. We used multivariable logistic regression and adjusted for potential confounders to determine the association of hypothyroidism with nonorgan-specific manifestations.14% of the sarcoidosis patients self-reported hypothyroidism and were generally middle-aged white women. Hypothyr...
Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine, Jan 10, 2006
MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control, Jan 4, 2009
This report updates and combines into one document earlier versions of guidelines for preventing ... more This report updates and combines into one document earlier versions of guidelines for preventing and treating opportunistic infections (OIs) among HIV-exposed and HIV-infected children, last published in 2002 and 2004, respectively. These guidelines are intended for use by clinicians and other health-care workers providing medical care for HIV-exposed and HIV-infected children in the United States. The guidelines discuss opportunistic pathogens that occur in the United States and one that might be acquired during international travel (i.e., malaria). Topic areas covered for each OI include a brief description of the epidemiology, clinical presentation, and diagnosis of the OI in children; prevention of exposure; prevention of disease by chemoprophylaxis and/or vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; and dis...
AIDS Research and Human Retroviruses, 2009
This was a proof-of-principle study to evaluate the impact of short cycle therapy (SCT; 4 days on... more This was a proof-of-principle study to evaluate the impact of short cycle therapy (SCT; 4 days on/3 days off) in adolescents and young adults with good viral suppression on a protease inhibitor-based antiretroviral regimen. Subjects were recruited by the Adolescent Trials Network for HIV/AIDS Interventions and the Pediatric AIDS Clinical Trials Group. Subjects were infected either through perinatal/early childhood transmission or later via risk behaviors. All subjects were required to have at least 6 months of documented viral suppression below 400 copies/ml plus a preentry value below 200 copies/ml and an entry CD4+ T cell count above 350 cells/mm3. Of the 32 subjects enrolled, 12 (37.5%) had confirmed viral load rebound >400 copies, with 18 subjects (56%) coming off for any reason. The majority of subjects resuppressed when placed back onto continuous therapy using the same agents. Although no difference was found in virologic rebound rates between the early and later transmission groups, those infected early in life had higher rates of coming off SCT for any reason. There was no impact of SCT on the CD4+ T cell counts in those who remained on study or those who came off SCT for any reason. Subjects demonstrated good adherence to the SCT regimen. This study suggests that further evaluation of SCT may be warranted in some groups of adolescents and young adults infected with HIV.
American Journal of Respiratory and Critical Care Medicine
RATIONALE Socioeconomic factors are associated with worse disease severity at presentation in sar... more RATIONALE Socioeconomic factors are associated with worse disease severity at presentation in sarcoidosis, but the relative importance of socioeconomic variables on morbidity and disease burden has not been fully elucidated. OBJECTIVES To determine the association between income and sarcoidosis outcomes after controlling for socioeconomic and disease-related factors. METHODS Using the Sarcoidosis Advanced Registry for Cures (SARC) database, we analyzed data from 2318 United States sarcoidosis patients to determine the effect of income and other variables on outcomes. We divided comorbidities arising after diagnosis into those likely related to steroid use and those likely related to sarcoidosis. We assessed the development of health-related, functional and socioeconomic outcomes following the diagnosis of sarcoidosis. MEASUREMENTS AND MAIN RESULTS In multivariate analysis, low income patients had significantly higher rates of new sarcoidosis related comorbidities [<$35,000 OR 2.4 (1.7-3.3), $35,000-$85,000 OR 1.4 (1.1-1.9), >$85,000 (REF)], new steroid related comorbidities [<$35,000 OR 1.3 (0.9-2.0), $35,000-$85,000 OR 1.5 (1.1-2.1), >$85,000 (REF)], had lower health-related quality of life as assessed by the Sarcoidosis Health Questionnaire (p<0.001) and experienced more impact on family finances [<$35,000 OR 7.9 (4.9-12.7), $35,000-$85,000 OR 2.7 (1.9-3.9), >$85,000 (REF)]. The use of supplemental oxygen, need for assistive devices, and job loss were more common in lower income patients. Development of comorbidities after diagnosis of sarcoidosis occurred in 63% of patients and were strong independent predictors of poor outcomes. In random forest modeling, income was consistently a leading predictor of outcome. CONCLUSIONS These results suggest the burden from sarcoidosis preferentially impacts the economically disadvantaged.
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Papers by Leslie Serchuck