Faculty Bibliography

The use of antiretroviral (ARV) medications has successfully reduced maternal transmission of human immunodeficiency virus (HIV)-1 to newborns, but metabolic and mitochondrial toxicities in newborns continue to be a concern. We report the case of a 10-day-old full-term female infant born to an HIV-positive mother presenting with lethargy and respiratory distress. Maternal ARV medications included nucleoside reverse transcriptase inhibitors (NRTIs) and an integrase strand transcriptase inhibitors (INSTIs). Infant ARV prophylaxis included two NRTIs and a nonnucleoside reverse transcriptase inhibitor. At presentation, laboratory tests were significant for hyponatremia, hyperkalemia, severe metabolic acidosis, and acute kidney injury. She was resuscitated with fluids and a stress dose of hydrocortisone (HC), which resulted in improvement of her condition within 48 h. Adrenal profile on the day of admission revealed elevated levels of 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, androstenedione, aldosterone, and elevated plasma renin activity. HC was tapered and the patient was discharged on the day of life (DOL) 26. Adrenocorticotropic hormone (ACTH) stimulation test off HC for one night that was performed on DOL31 showed a normal cortisol response of 35.8 mcg/dL at 60 min. HC was later discontinued. A repeat ACTH stimulation test off HC for 7 days that was performed on DOL59 yielded a normal cortisol response of 27.6 mcg/dL at 60 min. This report reveals severe metabolic disturbances suggestive of adrenal insufficiency (AI) in a neonate exposed to a combination of ARV medications in utero and postnatally with improvement of symptoms after glucocorticoid treatment. The AI was transient in nature, which resolved after cessation of ARV therapy.

BACKGROUND: Pediatric HIV has evolved from a pre-antiretroviral era (pre-1989 or Pre-ART) to an antiretroviral (ART) era (1989-1996) & to a highly active antiretroviral therapy (HAART) era (post-1996). As we have passed the 3rd decade following these individuals, we thought it useful to review clinical, laboratory, & social outcomes. METHODS: A retrospective, cross-sectional study of 399 children infected perinatally. They were divided into Pre-ART, ART & HAART groups. A Kaplan-Meier plot was constructed. 179 have been lost to follow-up at an average of 7.6 (0.3-27.6) years. RESULTS: Approximately 40, 80 and 90% of individuals in the Pre-ART, ART and HAART groups have long-term survival. 121 died at an average of 5.1 (0-26.1) years. Pre-ART, ART, & HAART groups had mean most recent CD4% values (+/-SEM) of 16.74(1.09), 22.97(0.96) & 33.07 (2.09), respectively (p<0.001). Pre-ART RNA is limited in that era and present if they survived to another era. In this group the median RNA values in those who died (311,300, n=16) was greater than in survivors (19,402, n=45). 43 % of the individuals in the ART group 77% of individuals in the HAART group had most recent HIV RNA<400 copies/ml.18 individuals >18 years of age have only a grade school or no education. 55 have graduated high school or received an equivalency diploma. 23 more have completed college. Nadir & recent CD4% of those who did & did not complete high school was equivalent to college graduates. 16 survivors (1/2 male) have had 18 uninfected children. CONCLUSIONS: This first long term follow-up study demonstrates remarkable survival and social skills of our patients.

Chronic granulomatous disease (CGD) is a rare, inherited immunodeficiency disorder that reduces the superoxide generation ability of phagocytes, leading to recurrent infections and granulomatous inflammation. We report the case of a previously healthy 3-year-old boy who presented with classic features of Crohn's disease. Suspicion from histopathological assessment allowed early diagnosis and treatment for CGD before the onset of infections.

Abstract Objective: This study aims to describe the final adult height (FAH) and pubertal growth patterns in human immunodeficiency virus (HIV)-infected adolescents and to compare these to an age-matched population of seroreverting HIV-exposed, uninfected (HEU) adolescents. It further aims to evaluate the interplay of proinflammatory cytokines with insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), and IGFBP-1 during the pubertal growth spurt. Methods: HIV-infected (n=34) and HEU (n=12) adolescents who had achieved FAH were evaluated. Auxologic data, viral load, CD4+ T-lymphocyte (CD4) count, and the use of highly active antiretroviral therapy were obtained via a retrospective chart review. Serum interleukin (IL)-1alpha, IL-6, tumor necrosis factor (TNF)-alpha, IGFBP-1, IGFBP-3, and IGF-1 were assessed. Results: The mean FAH standard deviation score for the HIV-infected group was -0.78 (+/-1.1) compared to 0.05 (+/-0.78) for the HEU (p=0.034). There was a positive correlation between CD4 count and FAH (p=0.019). The mean age and magnitude of peak growth velocity (GV) was within normal limits. IL-1alpha, IL-6, TNF-alpha, IGFBP-3, and IGF-1 were not significantly correlated with HIV RNA or height. IGFBP-1 was detectable in 100% of poorly controlled HIV-infected patients and 25% of the HEU cohort (p=0.0003). Conclusions: The FAH of HIV-infected patients was significantly shorter than that of HEU patients, and it positively correlated with CD4 count. Our cohort demonstrated normal timing and magnitude of peak GV during puberty.

Immune reconstitution inflammatory syndrome (IRIS) is a well-described complication of initiation of highly active antiretroviral therapy in HIV-infected patients. As the immune system recovers, an inappropriate inflammatory response often occurs that causes significant disease. It is most commonly seen in patients naive to therapy with CD4+ T-lymphocyte counts <100 cells/cmm and usually presents as a flare of mycobacterial, cytomegalovirus, or herpes zoster infections. Less commonly, this syndrome occurs in response to noninfectious triggers and results in autoimmune or malignant disease. Here we present the first case of acute poststreptococcal glomerulonephritis associated with varicella zoster virus and IRIS in an adolescent with perinatally acquired HIV and hepatitis C virus infections. Our patient was not naive to therapy but was starting a new regimen of therapy because of virologic failure and had a relatively high CD4+ T-lymphocyte count. This case report indicates that IRIS remains a concern after initiation of a new highly active antiretroviral therapy regimen in HIV-infected patients with high viral loads, even in the presence of CD4+ T-lymphocyte counts >100 cells/cmm. It may present as infectious, malignant, or autoimmune conditions including poststreptococcal glomerulonephritis.

We describe a case in which a human immunodeficiency virus (HIV)-positive child presented in severe metabolic acidosis secondary to his candidal sepsis and T-cell lymphoma, a rare finding in pediatric AIDS. Significantly elevated levels of Interleukin-10 (IL-10) were found in the patient's serum, which may have played a role in acute demise

BACKGROUND: Perinatally infected long-term nonprogressors/slow progressors represent a select group of individuals. There is very limited information on this group of children beyond the first decade of life. A group of HIV-infected long-term nonprogressor/slow progressor children was studied. METHODS: We enrolled 20 HIV-infected adolescents who were receiving no or minimal therapy (defined as single or dual nucleoside therapy) before the age of 10 years and who had maintained CD4 counts above 25% for the first decade of life. We analyzed immunologic and virologic characteristics. Thymic receptor excision circles (TREC) were measured on stored frozen peripheral blood mononuclear cells. CD4 count, viral load and other pertinent information including race and age were obtained from individual medical records. RESULTS: Nine of the 20 patients recruited were noted to have developed falling CD4 counts at or around puberty, whereas the other 11 remained stable. There was no difference in TREC values or HIV RNA values before or after puberty between the 2 groups of patients. Those who remained stable, in terms of maintaining CD4 T cells as a group had falling viral loads with age. Those whose CD4 values declined after puberty had viral loads that did not decrease with age. CONCLUSION: A select group of patients who never received HAART during their first decade of life will continue to maintain good CD4 associated with declining HIV RNA values. Thymic output is not predictive of those that don't maintain CD4 T cells

Children with acquired immunodeficiency syndrome (AIDS) are at an increased risk for lymphoproliferative and neoplastic disorders. Included among these are smooth muscle neoplasms such as leiomyomas and leiomyosarcomas. There have been at least 15 reported cases of smooth muscle tumors in the approximately 8,000 children with AIDS, however the incidence in immunocompetent children is only two per ten million. The lesions in children with human immunodeficiency virus infection are usually found in the lung, liver, and gastrointestinal tract. Here, we present an unusual case of a 12-year-old African American girl with vertically acquired AIDS who presented to the pediatric emergency department with severe diffuse abdominal pain. She was ultimately found to have an appendiceal leiomyoma on abdominal exploration, the first reported case. Our report suggests that smooth muscle tumors of the appendix be included in the differential diagnosis of abdominal masses in children with AIDS

BACKGROUND: CD8 cell responses to human immunodeficiency virus (HIV) have been correlated with virus control in adults, and this study outcome has been controversial. Attempts to establish the same correlation in small numbers of children have also been made, with similar controversy resulting. METHODS: A total of 110 perinatally infected children were studied. Nine of the children (mean age, 1.9 years vs. 11.8 years for the remaining 101 children) received treatment with antiretrovirals within the first 3 months of life. CD4 cell and HIV RNA levels were measured. Production of interferon- gamma after exposure to recombinant vaccinia vectors was measured by enzyme-linked immunospot (ELISPOT) assay. RESULTS: Responses to Pol and Gag antigens exceeded those to Nef and Env antigens, with responses significantly approximated by a quadratic function for which peak responses occurred at plasma HIV RNA levels of 103-104 HIV RNA copies/mL. Children who are treated early in life with highly active antiretroviral therapy have fewer total responses of ELISPOT-forming cells to HIV antigens than do children who are treated later in life