Patricia Whitley-Williams

Disclosure of illness status to children and adolescents with HIV infection

Many children with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome are surviving to middle childhood and adolescence. Studies suggest that children who know their HIV status have higher self-esteem than children who are unaware of their status. Parents who have disclosed the status to their children experience less depression than those who do not. This statement addresses our current knowledge and recommendations for disclosure of HIV infection status to children and adolescents.

Standards for adult immunization practices

Since the Standards for Adult Immunization Practices were first published in 1990, healthcare researchers and providers have learned important lessons on how to better achieve and maintain high vaccination rates in adults. The success rate of childhood immunization far exceeds the success rate of adult immunization. Thus, information and practices that will produce higher success rates for adult vaccination are crucial, resulting in overall societal cost savings and substantial reductions in hospitalizations and deaths. The Standards, which were developed to encourage the best immunization practices, represent the collective efforts of more than 100 people from more than 60 organizations. The revised Standards are more comprehensive than the 1990 Standards and focus on the accessibility and availability of vaccines, proper assessment of patient vaccination status, opportunities for patient education, correct procedures for administering vaccines, implementation of strategies to improve vaccination rates, and partnerships with the community to reach target patient populations. The revised Standards are recommended for use by all healthcare professionals and all public and private sector organizations that provide immunizations for adults. All who are involved in adult immunization should strive to follow the Standards in order to create the same level of success achieved by childhood vaccination programs and to meet the Healthy People 2010 goals.

The Data and Safety Monitoring Board and Acquired immune deficiency syndrome (AIDS) clinical trials

The urgency of the Acquired immune deficiency syndrome (AIDS) epidemic has mandated that multiple therapeutic approaches be developed and that these approaches be evaluated through clinical trials. To oversee these trials, the National Institute of Allergy and Infectious Diseases (NIAID) has created three large clinical trial programs monitored by a Data and Safety Monitoring Board (DSMB). For each clinical trial, this Board uses a standardized approach employing contemporary biostatistical, medical, and ethical principles. The DSMB is responsible for reviewing interim data on clinical trial performance, treatment safety and efficacy, and overall study progress. If interim results provide convincing evidence of either excessive adverse effects or significant treatment benefit, the DSMB may recommend early termination of the trial to the NIAID and the study investigators. The responsibility, organization, and operating procedures of this DSMB are presented and illustrated through three clinical trials sponsored by NIAID and monitored by the Board. The rationale and operational model for the DSMB may be a useful example for the development of similar review processes in other HIV clinical trial settings.

Evaluation and medical treatment of the HIV-exposed infant

As a result of the expanding human immunodeficiency virus (HIV) infection epidemic and recently published recommendations for routine HIV testing with consent for all pregnant women in the United States, pediatricians are becoming increasingly involved in providing care to infants born to HIV-infected women. This article provides guidelines about counseling the parent or care giver of the infant, use of antiretroviral therapy to reduce the risk of infection in the infant, medical treatment of the HIV-exposed infant, laboratory testing to determine the infection status of the infant, laboratory monitoring of hematologic and immunologic parameters, prophylaxis for Pneumocystis carinii pneumonia, and recommendations for immunizations and tuberculosis screening.

Emergence of Drug Resistance Mutations in a Group of HIV-Infected Children Taking Nelfinavir-Containing Regimens

HIV-1-infected children are often treated with therapy regimens including protease inhibitors (PIs). We monitored the virologic response in a small group of pediatric patients undergoing therapy with regimens including the PI nelfinavir and determined whether new drug resistance mutations were present immediately after virologic failure. Seventeen reverse transcriptase inhibitor (RTI)-experienced children starting nelfinavir-containing therapy regimens were studied. After virologic failure, HIV-1 protease (PR) and RT sequences were examined for drug resistance mutations. Viral load levels decreased to <400 HIV RNA copies/ml in six patients and remained at <400 HIV RNA copies/ml in four patients. Three patients did not respond virologically; all three had mutations specific for one or more of their regimen drugs either before or soon after nelfinavir initiation. The virologic response was transient in eight patients whose viral loads did not decrease to <400 HIV RNA copies/ml. Genotypic data from seven of the eight patients revealed mutations specific for one or more of their regimen drugs after virologic rebound. PI resistance mutations occurred in eight patients: D30N in six, and L90M in three. In three patients, the only new mutation after failure was the RT mutation M184V. Despite virologic failure, sustained increases in CD4+ lymphocyte counts were noted in eight patients. We conclude that in this small group of pediatric patients, virologic failure occurred in all patients whose viral loads did not become undetectable after the switch to a nelfinavir-containing regimen. After failure, new drug resistance mutations were found in either PR or RT. Studies of larger cohorts are warranted to determine whether HIV-1 genotypic data can help in the formulation of effective salvage therapies in children.

Clinical Immunology and Infectious Diseases

Without the application of immunology, understanding of the pathogenesis and pathophysiology of infectious diseases would be severely retarded. The development new vaccines for the prevention of infectious diseases has been based on new immunologic findings. Immunodiagnostic modalities have provided for the growth of diagnostic techniques for infectious diseases. Clinical immunology also has laid the groundwork for immunotherapies using the old intravenous immunoglobulin preparations and the new monoclonal antibodies, cytokines, and interferons.

Protease inhibitor associated mutations compromise the efficacy of therapy in human immunodeficiency virus – 1 (HIV-1) infected pediatric patients: a cross-sectional study

BackgroundAlthough the introduction of combined therapy with reverse transcriptase and protease inhibitors has resulted in considerable decrease in HIV related mortality; it has also induced the development of multiple drug-resistant HIV-1 variants.The few studies on HIV-1 mutagenesis in HIV infected children have not evaluated the impact of HIV-1 mutations on the clinical, virological and immunological presentation of HIV disease that is fundamental to optimizing the treatment regimens for these patients.ResultsA cross sectional study was conducted to evaluate the impact of treatment regimens and resistance mutation patterns on the clinical, virological, and immunological presentation of HIV disease in 41 children (25 male and 16 female) at the Robert Wood Johnson Pediatric AIDS Program in New Brunswick, New Jersey. The study participants were symptomatic and had preceding treatment history with combined ARV regimens including protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Fifteen (36.6%) children were treated with NRTI+NNRTI+ PI, 6 (14.6%) with NRTI+NNRTIs, 13 (31.7%) with NRTI+PIs, and the remaining 7 (17.1%) received NRTIs only.Combined ARV regimens did not significantly influence the incidence of NRTI and NNRTI associated mutations. The duration of ARV therapy and the childs age had no significant impact on the ARV related mutations. The clinico-immunological presentation of the HIV disease was not associated with ARV treatment regimens or number of resistance mutations. However, primary mutations in the protease (PR) gene increased the likelihood of plasma viral load (PVL) ≥ 10,000 copies/mL irrespective of the childs age, duration of ARV therapy, presence of NRTI and NNRTI mutation. Viremia ≥ 10,000 copies/mL was recorded in almost all the children with primary mutations in the PR region (n = 12/13, 92.3%) as compared with only 50.0% (n = 14/28) of HIV infected children without (PR-), P < 0.008. However, CD-4 T cells were not affected by the mutations in the PR gene of the HIV-1 isolates.ConclusionPrimary PR resistance mutations significantly increase the likelihood for high viral replication in pediatric patients with moderate/severe HIV-1 infection, which may affect the long-term clinical prognosis of the HIV infected children.

Treatment Response in Association with Adherence Patterns to Highly Active Antiretroviral Therapy in Pediatric Patients with Perinatally Acquired HIV Infection.

Background: Assessment of longitudinal adherence patterns on virologic and immunologic responses to HAART in perinatally acquired HIV patients has not been studied. Methods: Perinatally infected pediatric HIV patients with adherence documented at least twice and corresponding viral load and T-cell (%) data measured during 2008-2009 were studied. Multiple adherence measures were utilized to identify patients with persistent adherence, nonadherence, or alteration of adherence. Virologic and immunologic outcomes were assessed. Results: Persistent adherence, nonadherence, and alteration of adherence to HAART were recorded in 41.9%, 8.1%, and 50.0% of 62 studied patients. Persistent adherence was associated with higher likelihood for persistent virologic suppression and lower risk for persistent virologic failure. Conclusion: Alteration of adherence to HAART is a significant predictor of persistent virologic failure and high viremia in perinatally infected HIV patients. Implementation of longitudinal adherence assessments may target patients with nonsustained adherence patterns and help decrease the risk for virologic failure and disease progression.

Pediatric Hospital Medicine: A Proposed New Subspecialty

This article describes the challenges and opportunities that the American Board of Pediatrics had to consider in its recommendation to the American Board of Medical Specialties to recognize Pediatric Hospital Medicine as a new pediatric subspecialty. Over the past 20 years, hospitalists have emerged as a distinct group of pediatric practitioners. In August of 2014, the American Board of Pediatrics (ABP) received a petition to consider recommending that pediatric hospital medicine (PHM) be recognized as a distinct new subspecialty. PHM as a formal subspecialty raises important considerations related to: (1) quality, cost, and access to pediatric health care; (2) current pediatric residency training; (3) the evolving body of knowledge in pediatrics; and (4) the impact on both primary care generalists and existing subspecialists. After a comprehensive and iterative review process, the ABP recommended that the American Board of Medical Specialties approve PHM as a new subspecialty. This article describes the broad array of challenges and certain unique opportunities that were considered by the ABP in supporting PHM as a new pediatric subspecialty.

Rates of Neisseria Meningitidis: Increasing in Young Adults

The burden of meningococcal disease has remained unchanged in the United States for the past 4 decades. The currently available meningococcal vaccine is safe and effective, however, due to immunogenic limitations inherent to polysaccharide vaccines, it has been available only for high-risk populations older than 2. Incorporation of a more immunogenic and effective conjugated vaccine into the routine immunization schedule offers an opportunity to substantially affect the incidence of meningococcal disease. The routine use of a meningococcal conjugate vaccine in the United States will save lives and prevent significant morbidity in children and young adults.