Brief Report: Markers of Spontaneous Preterm Delivery in Women Living With HIV: Relationship With Protease Inhibitors and Vitamin D.

Background: Women living with HIV (WLHIV) have increased risk of spontaneous preterm delivery (SPTD). We sought to identify plasma predictors of SPTD and their correlations with factors that increase the risk of SPTD, such as vitamin D deficiency and use of protease inhibitors.

Design: Plasma was obtained from 103 WLHIV with SPTD (≤35 weeks gestation) and 205 controls with term deliveries (TDs; ≥37 weeds) matched to cases 2:1 by race and gestational age at blood draw.

Ophthalmic manifestations of perinatally acquired HIV in a US cohort of long-term survivors.

Background/aims: To determine the ophthalmic manifestations of HIV in a cohort of long-term survivors of perinatally acquired HIV.

Methods: Twenty-two patients with perinatally acquired HIV who were aged ≥12 years were prospectively studied at a university clinic. They underwent complete ophthalmic examinations and fundus photography.

Family adversity and autonomic reactivity association with immune changes in HIV-affected school children.

Objective: To explore whether primary school entry is associated with changes in immune system parameters in HIV-affected children. HIV-affected children are vulnerable to psychosocial stressors, regardless of their own HIV serological status.

Methods: Data from 38 HIV-positive and 29 HIV-negative children born to seropositive women were obtained.

The effect of prophylaxis on pediatric HIV costs.

The objective of this study was to determine and compare the cost to treat HIV(+) and HIV(-) pediatric patients both before and after HIV prophylaxis became the standard of care. Retrospective chart review of a pediatric HIV/AIDS specialty clinic's medical charts was conducted for clinical and healthcare utilization data on 125 children diagnosed from 1986 to 2007. Mean HIV-related costs were compared using bootstrapped t-tests for children born in the pre-prophylaxis (1979-1993) and prophylaxis eras (1994-2007).

Dendritic cells from humans with hypomorphic mutations in IKBKG/NEMO have impaired mitogen-activated protein kinase activity.

The covalent attachment of lysine 63-linked polyubiquitin to the zinc-finger domain of IKBKG/NEMO (also known as IKKγ) is necessary for full activation of NF-κB. Impairments of this biochemical mechanism explain the deleterious effects of hypomorphic NEMO mutations on NF-κB signaling function in humans suffering from X-linked ectodermal dysplasia and immunodeficiency. Nevertheless, the biological function of the NEMO zinc-finger domain in the regulation of mitogen-activated protein kinase (MAPK) activity is poorly understood.

Pediatric HIV costs across three treatment eras from 1986 to 2007.

Objective: Life has changed dramatically for infants exposed perinatally to HIV to HIV primarily because of a successful translational research program that has also affected treatment costs. We compared treatment costs among HIV+ patients in an HIV/AIDS specialty clinic across 3 treatment eras: monotherapy (pre-1990), combination therapy (1990-1996), and highly active antiretroviral therapy (HAART) (1997-2007). We also estimated cumulative health care costs among pediatric HIV/AIDS patients born in each era.

Anti-influenza serum and mucosal antibody responses after administration of live attenuated or inactivated influenza vaccines to HIV-infected children.

Background: Live-attenuated influenza vaccine (LAIV) prevents more cases of influenza in immune-competent children than the trivalent inactivated vaccine (TIV). We compared the antibody responses to LAIV or TIV in HIV-infected children.

Methods: Blood and saliva obtained at enrollment, 4 and 24 weeks postimmunization from 243 HIV-infected children randomly assigned to TIV or LAIV were analyzed.

Persistent systemic inflammation and atypical enterocolitis in patients with NEMO syndrome.

The NEMO syndrome is a primary immunodeficiency with immune and non-immune manifestations. The immune deficiency is heterogeneous showing defects in humoral, innate, and cell-mediated immunity. While the clinical aspects of the immunodeficiency are increasingly well understood, little is known about autoimmune manifestations in NEMO patients.

Altered iron metabolism in children with human immunodeficiency virus disease.

Background: Despite the high prevalence of altered iron metabolism in children with human immunodeficiency virus (HIV) disease, these alterations have not been well studied.

Procedures: Twenty-six children with HIV disease underwent laboratory evaluation to determine the presence of anemia, and to classify the anemia as iron-deficiency anemia or anemia of chronic disease.

Results: Half of the children had an alteration in iron metabolism: 6 were iron deficient, 4 had hyperferritinemia, and 3 demonstrated hyperferritinemia with iron deficiency.

Regulatory T cells and their role in rheumatic diseases: a potential target for novel therapeutic development.

Regulatory T cells have an important role in limiting immune reactions and are essential regulators of self-tolerance. Among them, CD4+CD25high regulatory T cells are the best-described subset. In this article, we summarize current knowledge on the phenotype, function, and development of CD4+CD25high regulatory T cells.

Population pharmacokinetics of lamivudine in human immunodeficiency virus-exposed and -infected infants.

This study aimed to determine lamivudine disposition in infants and to construct an appropriate dose adjustment for age, given the widespread use of lamivudine for both the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) and the treatment of HIV-infected infants. Using a pooled-population approach, the pharmacokinetics of lamivudine in HIV-exposed or -infected infants from four Pediatric AIDS Clinical Trials Group studies were assessed. Ninety-nine infants provided 559 plasma samples for measurement of lamivudine concentrations.

JC virus granule cell neuronopathy in a child with CD40 ligand deficiency.

JC virus infection of the brain typically causes progressive multifocal leukoencephalopathy, a demyelinating disease that rarely involves gray matter. This report presents a case of cerebellar degeneration associated with JC virus infection in a male with CD40 ligand deficiency resulting in hyperimmunoglobulin M type 1. This patient exhibited a progressive cerebellar ataxia with progressive atrophy of the cerebellar cortex in association with the presence of JC virus in the spinal fluid.

Pharmacokinetics and safety of indinavir in human immunodeficiency virus-infected pregnant women.

Human immunodeficiency virus-infected women (n=16) received indinavir (800 mg three times a day) plus zidovudine plus lamivudine from 14 to 28 weeks of gestation to 12 weeks postpartum. Two women and eight infants experienced grade 3 or 4 toxicities that were possibly treatment related. Indinavir area under the plasma concentration-time curve was 68% lower antepartum versus postpartum, suggesting increased intestinal and/or hepatic CYP3A activity during pregnancy.

Impaired integrin-dependent function in Wiskott-Aldrich syndrome protein-deficient murine and human neutrophils.

Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency that manifests as increased susceptibility to many pathogens. Although the spectrum of infections suffered by WAS patients is consistent with defects in neutrophil (PMN) function, the consequences of WAS protein (WASp) deficiency on this innate immune cell have been unclear. We report that deficiency of WASp in both human and murine PMNs resulted in profound defects in clustering of beta2 integrins, leading to defective adhesion and transendothelial migration under conditions of physiologic shear flow.

Antibody responses to hepatitis A virus vaccine in HIV-infected children with evidence of immunologic reconstitution while receiving highly active antiretroviral therapy.

Background: Human immunodeficiency virus (HIV)-infected patients have weak responses to vaccines and may require revised immunization regimens. We investigated the safety and immunogenicity of 2 doses of hepatitis A virus (HAV) vaccine followed by a booster dose in HIV-infected children receiving stable highly active antiretroviral therapy.

Methods: A total of 235 children with CD4+ T cell percentages > or = 20% received 2 vaccine doses 24 weeks apart, and 117 received a third vaccine dose after 104 weeks.

Long-term efficacy of enzyme replacement therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID).

Adenosine deaminase (ADA)-deficient Severe Combined Immunodeficiency (ADA-deficient SCID) is characterized by impaired lymphocyte development and function resulting from the adenosine metabolism defect. Enzyme replacement therapy with polyethylene glycol-conjugated adenosine deaminase (PEG-ADA) minimizes infectious complications of ADA-deficient patients who have not received bone marrow transplantation. In PEG-ADA therapy, enzymatically active ADA continuously circulates to act as a metabolic sink, detoxifying the adenosine and deoxyadenosine metabolites that accumulate to high levels in the absence of ADA.

Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study.

Background: Peripheral blood lymphocyte subsets need to be determined in a large, urban, minority-predominant cohort of healthy children to serve as suitable control subjects for the interpretation of the appearance of these cells in several disease conditions, notably pediatric HIV-1 infection.

Objective: We sought to determine the distribution of lymphocyte subsets in healthy urban-dwelling infants, children, and adolescents in the United States.

Methods: Lymphocyte subsets were determined by means of 3-color flow cytometry in a cross-sectional study of 807 HIV-unexposed children from birth through 18 years of age.

When the time comes to talk about HIV: factors associated with diagnostic disclosure and emotional distress in HIV-infected children.

Objective: To determine factors related to the timing and probability of nondisclosure of HIV status to perinatally HIV-infected children, and to explore factors associated with emotional distress in HIV-infected children.

Methods: This is a cross-sectional study of 51 HIV-infected children based on medical records, parent interviews, and child assessments.

Results: 1) Probability of earlier age of disclosure is associated with higher child IQ (p =.

Increasing women's leadership in academic medicine: report of the AAMC Project Implementation Committee.

The AAMC's Increasing Women's Leadership Project Implementation Committee examined four years of data on the advancement of women in academic medicine. With women comprising only 14% of tenured faculty and 12% of full professors, the committee concludes that the progress achieved is inadequate. Because academic medicine needs all the leaders it can develop to address accelerating institutional and societal needs, the waste of most women's potential is of growing importance.

Antiretroviral therapy during pregnancy and the risk of an adverse outcome.

Background: Some studies suggest that combination antiretroviral therapy in pregnant women with human immunodeficiency virus type 1 (HIV-1) infection increases the risk of premature birth and other adverse outcomes of pregnancy.

Methods: We studied pregnant women with HIV-1 infection who were enrolled in seven clinical studies and delivered their infants from 1990 through 1998. The cohort comprised 2123 women who received antiretroviral therapy during pregnancy (monotherapy in 1590, combination therapy without protease inhibitors in 396, and combination therapy with protease inhibitors in 137) and 1143 women who did not receive antiretroviral therapy.

Human immunodeficiency virus type 1 (HIV-1) gp120-specific antibodies in neonates receiving an HIV-1 recombinant gp120 vaccine.

Infants born to human immunodeficiency virus type 1 (HIV-1)-infected mothers were immunized at birth and at ages 4, 12, and 20 weeks with low-, medium-, or high-dose recombinant gp120 vaccine with MF59 adjuvant (HIV-1(SF-2); n=52) or with MF59 alone as a placebo (n=9). An accelerated schedule (birth and ages 2, 8, and 20 weeks) was used for an additional 10 infants receiving the defined optimal dose and for 3 infants receiving placebo. At 24 weeks, anti-gp120 ELISA titers were greater for vaccine-immunized than for placebo-immunized infants on both schedules, and 87% of vaccinees had a vaccine-induced antibody response.