Long-term virologic and immunologic responses in human immunodeficiency virus type 1-infected children treated with indinavir, zidovudine, and lamivudine.

Virologic and immunologic responses were examined for 33 human immunodeficiency virus (HIV)-infected children who participated for > or = 96 weeks in a phase 1/2 protocol of 16 weeks of indinavir monotherapy, followed by the addition of zidovudine and lamivudine. At week 96, a median increase of 199 CD4+ T cells/microL and a median decrease of 0.74 log(10) HIV RNA copies/mL were observed. The relationship between control of viral replication and CD4) T cell count was examined. Patients were categorized into 3 response groups on the basis of duration and extent of control of viral replication. Of 21 children with a transient decrease in virus load of > or = 0.7 log(10) HIV RNA copies/mL from baseline, 7 experienced sustained increases in CD4+, CD4+ CD45RA+, and CD4+ CD45RO+ T cell counts. CD4+ CD45RA+ (naive) T cells were the major contributor to CD4+ T cell expansion. Continued long-term immunologic benefit may be experienced by a subset of children, despite only transient virologic suppression.

Esophageal candidiasis in pediatric acquired immunodeficiency syndrome: clinical manifestations and risk factors.

BACKGROUND: Little is known about the epidemiology and clinical features of esophageal candidiasis (EC) in pediatric AIDS. We therefore investigated the clinical presentation and risk factors of EC in a large prospectively monitored population of HIV-infected children at the National Cancer Institute. PATIENTS AND METHODS: We reviewed the records of all HIV-infected children (N = 448) followed between 1987 and 1995 for a history of esophageal candidiasis to characterize the epidemiology, clinical features, therapeutic interventions and outcome of esophageal candidiasis. To understand further the risk factors for EC in pediatric AIDS, we then performed a matched case-control analysis of 25 patients for whom control cases were available. RESULTS: There were 51 episodes of EC documented in 36 patients with 23 male and 13 female patients (0.2 to 17 years; median CD4, count 11/microl), representing a frequency of EC of 8.0%. Concurrent oropharyngeal candidiasis (OPC) was the most common clinical presentation of EC (94%); other signs and symptoms included odynophagia (80%), retrosternal pain (57%), fever (29%), nausea/vomiting (24%), drooling (12%), dehydration (12%), hoarseness (6%) and upper gastrointestinal bleeding (6%). The causative organism documented in 36 episodes (18 from OPC, 17 from endoscopic biopsy and 1 from autopsy) was Candida albicans in all cases. Patients received treatment for EC with amphotericin B (63%), fluconazole (29%), ketoconazole (4%) or itraconazole (1%). A clinical response was documented in all 45 evaluable episodes. In 6 other cases, EC was a final event without contributing to the cause of death. By a conditional logistic regression model for matched data, the best predictor of EC was the presence of prior OPC (P<0.0001), followed by CD4 count and CD4 percentage (P = 0.0002) and use of antibacterial antibiotics (P = 0.0013). The risks associated with low CD4 count were independent of that of prior OPC. CONCLUSION: EC in pediatric AIDS is a debilitating infection, which develops in the setting of prior OPC, low CD4 counts and previous antibiotics.

A double-blind comparison of empirical oral and intravenous antibiotic therapy for low-risk febrile patients with neutropenia during cancer chemotherapy.

BACKGROUND: Among patients with fever and neutropenia during chemotherapy for cancer who have a low risk of complications, oral administration of empirical broad-spectrum antibiotics may be an acceptable alternative to intravenous treatment. METHODS: We conducted a randomized, double-blind, placebo-controlled study of patients (age, 5 to 74 years) who had fever and neutropenia during chemotherapy for cancer. Neutropenia was expected to be present for no more than 10 days in these patients, and they had to have no other underlying conditions. Patients were assigned to receive either oral ciprofloxacin plus amoxicillin-clavulanate or intravenous ceftazidime. They were hospitalized until fever and neutropenia resolved. RESULTS: A total of 116 episodes were included in each group (84 patients in the oral-therapy group and 79 patients in the intravenous-therapy group). The mean neutrophil counts at admission were 81 per cubic millimeter and 84 per cubic millimeter, respectively; the mean duration of neutropenia was 3.4 and 3.8 days, respectively. Treatment was successful without the need for modifications in 71 percent of episodes in the oral-therapy group and 67 percent of episodes in the intravenous-therapy group (difference between groups, 3 percent; 95 percent confidence interval, -8 percent to 15 percent; P=0.48). Treatment was considered to have failed because of the need for modifications in the regimen in 13 percent and 32 percent of episodes, respectively (P<0.001) and because of the patient's inability to tolerate the regimen in 16 percent and 1 percent of episodes, respectively (P<0.001). There were no deaths. The incidence of intolerance of the oral antibiotics was 16 percent, as compared with 8 percent for placebo (P=0.07). CONCLUSIONS: In hospitalized low-risk patients who have fever and neutropenia during cancer chemotherapy, empirical therapy with oral ciprofloxacin and amoxicillin-clavulanate is safe and effective.

A phase I/II study of the protease inhibitor indinavir in children with HIV infection.

BACKGROUND: Indinavir, an inhibitor of the human immunodeficiency virus type 1 (HIV-1) protease, is approved for the treatment of HIV infection in adults when antiretroviral therapy is indicated. We evaluated the safety and pharmacokinetic profile of the indinavir free-base liquid suspension and the sulfate salt dry-filled capsules in HIV-infected children, and studied its preliminary antiviral and clinical activity in this patient population. In addition, we evaluated the pharmacokinetic profile of a jet-milled suspension after a single dose. METHODS: Previously untreated children or patients with progressive HIV disease despite antiretroviral therapy or with treatment-associated toxicity were eligible for this phase I/II study. Three dose levels (250 mg/m2, 350 mg/m2, and 500 mg/m2 per dose given orally every 8 h) were evaluated in 2 age groups (<12 years and >/=12 years). Indinavir was initially administered as monotherapy and then in combination with zidovudine and lamivudine after 16 weeks. RESULTS: Fifty-four HIV-infected children (ages 3.1 to 18.9 years) were enrolled. The indinavir free-base suspension was less bioavailable than the dry-filled capsule formulation, and therapy was changed to capsules in all children. Hematuria was the most common side effect, occurring in 7 (13%) children, and associated with nephrolithiasis in 1 patient. The combination of indinavir, lamivudine, and zidovudine was well tolerated. The median CD4 cell count increased after 2 weeks of indinavir monotherapy by 64 cells/mm3, and this was sustained at all dose levels. Plasma ribonucleic acid levels decreased rapidly in a dose-dependent way, but increased toward baseline after a few weeks of indinavir monotherapy. CONCLUSIONS: Indinavir dry-filled capsules are relatively well tolerated by children with HIV infection, although hematuria occurs at higher doses. Future studies need to evaluate the efficacy of indinavir when combined de novo with zidovudine and lamivudine.

Protease inhibitor and triple-drug therapy: cellular immune parameters are not restored in pediatric AIDS patients after 6 months of treatment.

OBJECTIVE: To assess whether treatment of HIV-positive children by antiretroviral drugs for a 6-month period would improve immune function significantly. DESIGN AND METHODS: Immunological assessment of 89 HIV-positive children who received protease inhibitor monotherapy for 12-16 weeks as part of phase I/II studies, followed by triple antiretroviral therapy for an additional 12 weeks, was conducted. Immunological parameters were assessed in vitro at four time points (at enrollment, at weeks 2-4, at weeks 12-16, and at weeks 24-28). Assessments included: cytokine production by monocytes, T-cell proliferation to mitogen or recall antigens (including an HIV antigen) and apoptotic cell death. Plasma levels of tumor necrosis factor (TNF)-alpha and soluble TNF receptor (sTNF-R) were also measured, in addition to CD4+ T-lymphocyte counts and viral load. In addition, limited analyses were performed on samples from 17 children after 120 weeks of therapy, including 104 weeks of triple therapy. RESULTS: At enrollment, the 89 children exhibited severe immune defects. Antiretroviral therapy raised CD4+ T-lymphocyte counts significantly and decreased viral loads. In contrast, the in vitro immune parameters studied were not improved, except for plasma levels of sTNF-RII which decreased in parallel with the decrease in viral load. In addition, there was a trend towards increased skin test reactivity for the ritonavir-treated children. No differences were seen in the immune parameters whether the patients were treated with mono- or triple therapy. Results obtained after 120 weeks of therapy demonstrated that defective interleukin-12 production was not restored by long-term therapy. CONCLUSIONS: After 6 months of therapy, with the exception of decreased sTNF-RII levels, and a trend towards increased skin test reactivity, restoration of several defective cellular immune responses did not occur despite significantly decreased viral loads and increased CD4+ T-lymphocyte counts.

Safety, tolerance, and pharmacokinetics of amphotericin B lipid complex in children with hepatosplenic candidiasis.

The safety, tolerance, and pharmacokinetics of amphotericin B lipid complex (ABLC) were studied in a cohort of pediatric cancer patients. Six children with hepatosplenic candidiasis (HSC) received 2.5 mg of ABLC/kg of body weight/day for 6 weeks for a total dosage of 105 mg/kg. Mean serum creatinine (0.85 +/- 0.12 mg/dl at baseline) was stable at the end of therapy at 0.85 +/- 0.18 mg/dl and at 1-month follow-up at 0.72 +/- 0.12 mg/dl. There was no increase in hepatic transaminases. Mean plasma concentrations over the dosing interval (C(ave)) and area under the curve from 0 to 24 h (AUC(0-24h)) increased between the first and seventh doses but were similar between doses 7 and 42, suggesting that steady state was achieved by day 7 of therapy. Following the final (42nd) dose of ABLC, mean AUC(0-24h) was 11.9 +/- 2.6 microg h/ml, C(ave) was 0.50 +/- 0.11 microg/ml, maximum concentration of the drug in whole blood was 1.69 +/- 0.75 microg/ml, and clearance was 3.64 +/- 0.78 ml/min/kg. Response of hepatic and splenic lesions was monitored by serial computerized tomographic and magnetic resonance imaging scans. The five evaluable patients responded to ABLC with complete or partial resolution of physical findings and of lesions of HSC. During the course of ABLC infusions and follow-up, there was no progression of HSC, breakthrough fungemia, or posttherapy recurrence. Hepatic lesions continued to resolve after the completion of administration of ABLC. Thus, ABLC administered in multiple doses to children was safe, was characterized by a steady state attainable within 1 week of therapy, and was effective in treatment of HSC.

Multilocular thymic cysts in children with human immunodeficiency virus infection: clinical and pathologic aspects.

BACKGROUND: Children with human immunodeficiency virus (HIV) infection have an increased susceptibility to severe and unusual infections, malignancies, and disorders characterized by abnormal lymphoproliferation (e.g., lymphoid interstitial pneumonitis). We report a novel disease entity associated with pediatric HIV infection that is characterized by massive enlargement of the thymus as a result of lymphoid hyperplasia and multicystic changes. METHODS: Eight patients with HIV infection and cystic enlargement of the thymus are subject of this report. The status of their HIV disease and its clinical and radiologic manifestations at the time of diagnosis of the mediastinal mass are described. Tissue specimens were obtained from six patients and examined by microscopy and immunohistochemistry. The specimens were also evaluated for the evidence of HIV and Epstein-Barr virus by in situ hybridization. RESULTS: Patients were between 2.1 and 12.1 years of age, with CD4+ cell counts between 102 and 733 cells/mm3. In all eight cases an anterior mediastinal mass was discovered incidentally on radiography of the chest, and computed tomography of the chest revealed a multicystic appearance. Histologic examination demonstrated distortion of the thymic architecture by focal cystic changes, lymphoid follicular hyperplasia, diffuse plasmacytosis, and multinucleated giant cells. In situ hybridization revealed HIV particles on the surface of follicular dendritic cells. Further, results of in situ hybridization for EBV were positive in lymphoid cells from biopsy samples of four patients. The patients were followed between 8 months and 4.8 years. In five patients the mass either decreased in size or resolved completely. CONCLUSIONS: We describe a series of children with HIV infection and multilocular thymic cysts. We hypothesize that aberrant immunoregulation in these HIV-infected children leads to follicular hyperplasia and multicystic changes in the thymus, causing massive enlargement. EBV infection might also contribute to the pathogenesis of this process. Because none of our patients had symptoms from the mass, and there was no evidence of malignancy in the examined biopsy samples, it seems prudent to manage such children with careful follow-up examinations.

Cytomegalovirus infection in children with human immunodeficiency virus infection.

OBJECTIVES: To determine retrospectively the prevalence of positive cytomegalovirus (CMV) cultures in pediatric patients with human immunodeficiency virus infection. METHODS: We reviewed the records of 273 children with human immunodeficiency virus infection referred to the Pediatric Branch of the National Cancer Institute for whom CMV cultures were performed between January, 1991, and October, 1994. RESULTS: Of this group 189 patients (69%) had negative CMV cultures and 84 (31%) had positive cultures. The prevalence of CMV-related disease was 9% for the entire group, including 4 (2.1%) patients with negative CMV cultures. Among the 84 patients with positive CMV cultures, 21 (25%) had evidence of CMV disease. Patients with positive CMV cultures had a statistically significant decrease in survival in the presence of severe immunocompromise defined as an age-corrected CD4 count of < 21%. Nine of 35 (26%) autopsies performed demonstrated evidence of CMV disease, including 7 patients with disseminated CMV disease. CONCLUSIONS: Although CMV disease appears to be less frequent in children than adults, CMV infection still contributes significantly to morbidity and mortality in this population, especially when combined with severe immunosuppression.

Invasive aspergillosis in human immunodeficiency virus-infected children.

BACKGROUND: Aspergillosis is an uncommon yet serious opportunistic infection in patients with AIDS. It has been extensively reported in HIV-infected adult patients. To our knowledge there are no studies that describe the epidemiology, clinical manifestations and outcome of aspergillosis in a large HIV-infected pediatric population. METHODS: We reviewed the records of all 473 HIV-infected children followed in the Pediatric Branch of the National Cancer Institute for 9 years from 1987 through 1995 for the presence of Aspergillus infection. RESULTS: Seven (1.5%) patients developed invasive aspergillosis during the study period. All patients had low CD4 counts reflecting severe immunosuppression. Sustained neutropenia (> 7 days) or corticosteroid therapy as a predisposing factor for invasive aspergillosis was encountered in only two patients (28%). Invasive pulmonary aspergillosis developed in five patients and cutaneous aspergillosis in two. The most common presenting features in patients with pulmonary aspergillosis were fever, cough and dyspnea. Patients with cutaneous aspergillosis were diagnosed during life and successfully treated with amphotericin B and surgery, whereas diagnosis of pulmonary aspergillosis was made clinically in only one patient. CONCLUSIONS: Aspergillosis is an uncommon but highly lethal opportunistic infection in HIV-infected children. Invasive pulmonary aspergillosis should be considered in the differential diagnosis in febrile, HIV-infected children with persistent pulmonary infiltrates.

Infectious complications of patients undergoing therapy for acute leukemia: current status and future prospects.

The success of managing the infectious complications of acute leukemia has permitted oncologists to develop new approaches to induction and high-dose therapy. The single most important risk factor for infection is the duration of absolute neutropenia. Historically, most attention was directed towards gram negative aerobes, especially Pseudomonas aeruginosa, but in recent years gram positive bacteria, generally considered to be less virulent, have become the most frequent isolates in most centers. A recent disturbing trend is the isolation of vancomycin-resistant enterococci. A recent controversy has been whether to use empirical vancomycin; the Centers for Disease Control has issued a formal recommendation discouraging empirical vancomycin in the febrile neutropenic patient. Empirical monotherapy has replaced combination therapy in many institutions except where there has been an increase in resistant isolates. In patients who remain profoundly neutropenic, fungal infections represent a serious source of secondary infection, especially species of Candida and Aspergillus. Recently lipid-based formulations of amphotericin B have offered reduced nephrotoxicity. Less toxic antifungals, the azoles, which include fluconazole and itraconazole, offer an attractive alternative to amphotericin B. New patterns of invasive mycoses have emerged, as for example hepatosplenic candidiasis, presenting new problems in diagnosis and therapy. The successful management of virus infections with herpes simplex, cytomegalovirus, varicella zoster, and Epstein Barr virus is based on early recognition and careful attention to prevention.

IL-10 exerts suppressive and enhancing effects on antifungal activity of mononuclear phagocytes against Aspergillus fumigatus.

Invasive aspergillosis has emerged as a frequent and serious infection in immunocompromised patients. We studied the effects of human IL-10 on antifungal activity of monocytes (MNCs) from healthy adults against Aspergillus fumigatus after incubation with IL-10 at 37 degrees C for 2 to 4 days. IL-10 (2-20 ng/ml)-pretreated MNCs exhibited approximately 40% suppression of superoxide anion (02-) production in response to PMA and FMLP (p < or = 0.003), and anti-IL-10 containing supernatant neutralized the IL-10 effect. IL-10 (20 ng/ml)-pretreated MNCs exhibited decreased damage of Aspergillus hyphae after 2 to 4 days (55-98% decrease, p < or = 0.04). The MNC phagocytic activity against conidia, as assessed by microscopy (percentage of phagocytosing MNCs and number of intracellular conidia per MNC) as well as by colony counting (colonies grown from intracellular conidia), was enhanced by 127% (p = 0.006), 14% (p = 0.03), and 23% (p = 0.009), respectively. MNC capacity to inhibit intracellular germination was marginally enhanced (p = 0.04) and intracellular conidiocidal activity was unaffected by IL-10. IL-4 (5 ng/ml) did not change the up-regulatory IL-10 effect on phagocytosis. IFN-gamma (25 ng/ml) and granulocyte-macrophage CSF (20 ng/ml), but not macrophage CSF (15 ng/ml), appeared to counteract suppressive IL-10 effects. Thus, IL-10 suppresses oxidative burst and antifungal activity of MNCs against Aspergillus hyphae, while increasing their phagocytic activity. These findings further elucidate a potential role of IL-10 in the pathogenesis of invasive aspergillosis, which may lead to new treatment strategies.

Multilocular thymic cysts: imaging features in children with human immunodeficiency virus infection.

PURPOSE: To evaluate the radiologic and follow-up features of multilocular thymic cysts in children with human immunodeficiency virus (HIV) infection. MATERIALS AND METHODS: Four HIV-infected children with large anterior mediastinal masses depicted at routine chest radiography underwent ultrasonography (US), unenhanced and contrast material-enhanced computed tomography (CT), and unenhanced and gadolinium-enhanced MR imaging of the chest. Gallium scanning was also performed in three of the four children. The patients underwent follow-up radiologic examinations for 8-15 months. RESULTS: The multiloculated nature of the masses was depicted at contrast-enhanced but not unenhanced CT. Similarly, the septations were depicted on T2-weighted, short inversion time inversion-recovery (STIR), and contrast-enhanced T1-weighted, MR images but not on the unenhanced T1-weighted images. US scans depicted the septations within each mass, but findings were technically limited because only portions of each mass were depicted. Gallium scans in three masses depicted uptake of radionuclide in two and no uptake in one. Surgical biopsy was performed in each mass: Follicular hyperplasia and diffuse plasmacytosis of the thymus were found but not evidence of neoplastic or infectious origin. At follow-up, the mass decreased in volume in two patients, did not change in one patient, and increased in volume in one patient. CONCLUSION: HIV-infected patients with asymptomatic mediastinal masses depicted at routine chest radiography should undergo contrast-enhanced CT. If a solid mass is depicted, biopsy should be performed to exclude neoplastic or infectious origins. If a multiloculated anterior mediastinal mass is depicted, symptomatic follow-up is adequate since the finding represents a rare multilocular thymic cyst that does not have negative clinical implications.

Factors associated with disclosure of diagnosis to children with HIV/AIDS.

Disclosure of the diagnosis of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) to a child is a controversial and emotionally laden issue. To understand the factors that affect the process of disclosure and its consequences, we studied 99 parent-child dyads recruited from patients being treated at the National Cancer Institute (NCI). Parents and HIV-infected children were interviewed and administered several standardized measures. Parental depression, family environment, social support satisfaction, socioeconomic status, child and parent gender, child's age, parental HIV serostatus, and disease severity were used to predict disclosure status. Results indicate that the majority of caregivers do disclose the diagnosis to the child, usually with no ill effects, and that age is the most significant predictor of whether or not a child has been told. The Centers for Disease Control and Prevention currently estimate that there are over 6611 children with AIDS (under age 13), and 2184 adolescents with AIDS (ages 13-19) in America. As an increasing number of children who are born infected with HIV live to older ages, the question of when and how to talk with them about their illness becomes more crucial. In addition to the growing number of children infected with HIV, there are many thousands of children profoundly affected by the impact of this disease on a close family member--a mother, father, sibling, or other relative in the kinship network. Yet, the initial reaction most adults have upon learning of their own, or of a family member's, HIV diagnosis is that the diagnosis must be kept a closely guarded secret. One reason frequently cited by parents and family members is their fear that the stigma of AIDS will have a negative impact on their children and their families. Disclosure of an HIV diagnosis to a child is a controversial and emotionally laden issue in the pediatric health-care community as well. However, no systematic research has studied the issues that surround disclosure of an HIV diagnosis to the patient and the factors that predict disclosure.

Comparison of virus burden in blood and sequential lymph node biopsy specimens from children infected with human immunodeficiency virus.

BACKGROUND: Lymph nodes serve as reservoirs for the replication of human immunodeficiency virus (HIV) type 1. Comparison of serial measurements of virus burden in lymph nodes and peripheral blood after a change in antiretroviral therapy may provide insights into pathogenic mechanisms and permit a more accurate assessment of a therapeutic response. STUDY DESIGN: Nevirapine was added to the drug regiment of eight children with HIV infection treated with the combination of zidovudine and didanosine who had increasing levels of serum p24 antigen. Lymph node biopsies were performed at entry and after 12 weeks of therapy. RESULTS: Neither CD4 counts nor p24 antigen level correlated with the degree of viremia as measured by ribonucleic acid copy numbers in plasma. Correlations were found between HIV DNA copy number in peripheral blood mononuclear cells and HIV DNA copy number in lymph nodes (p = 0.02), as well as between peripheral blood CD4 counts and lymph node architecture. The HIV signals in the lymph nodes conformed to the anatomic organization of apical light zones in the germinal centers; however, in more advanced disease stages, organized germinal centers disappeared as evidence by a decline in the extent of the follicular dendritic network. CONCLUSIONS: Lymph node biopsies in this small number of HIV-infected children revealed a progressive loss of an organized architecture, especially of the follicular dendritic network. This correlated with a progressive loss of CD4+ cells but not with other measures of disease stage, including viral load, as measured by ribonucleic acid copy numbers.

Cryptococcosis in human immunodeficiency virus-infected children.

BACKGROUND: Cryptococcosis is a common opportunistic infection in adults with AIDS. Few cases of cryptococcosis complicating pediatric AIDS have been reported. To our knowledge there are no studies that describe the epidemiology, clinical manifestations and outcome of cryptococcosis in a large population of HIV-infected children. METHODS: We identified the cases of cryptococcosis through a retrospective review of the hospital records of the 473 HIV-infected children prospectively monitored in the Pediatric Branch of the National Cancer Institute during the 8 years from 1987 to 1995. RESULTS: Four (0.85%) patients developed cryptococcosis during the study period. All patients had profound depression of the absolute CD4 counts, a history of previous opportunistic infections, and onset of cryptococcosis in the second decade of life. Cryptococcosis developed as a disseminated infection or a localized process of the lungs. Intermittent fever was the most common presenting manifestation. Serum cryptococcal antigen was positive in all patients and gradually declined after the institution of the antifungal therapy. All patients were treated with amphotericin B with or without flucytosine as initial therapy. Suppressive therapy consisted of fluconazole with or without flucytosine. There were no deaths due to Cryptococcus neoformans. CONCLUSIONS: Cryptococcosis is an infrequent yet treatable opportunistic infection of advanced pediatric AIDS that may present with subtle manifestations and warrants careful consideration in the evaluation of febrile HIV-infected children.

Risk factors for fungemia in children infected with human immunodeficiency virus: a case-control study.

To define the risk factors related to the occurrence of fungemia in children infected with human immunodeficiency virus (HIV), we performed a matched case-control study. During a 6-year period (1987-1993), fungemia developed in 22 (6.3%) of 347 HIV-infected children observed at the Pediatric Branch of the National Cancer Institute. Each of these 22 cases was matched by age and gender with three controls. Multiple logistic regression indicated that the best predictor of fungemia in this population was the presence of a central venous catheter placed for > 90 days (P < .00001), followed by a group of risk factors composed of 10 independent variables adjusted for a CD4 cell count of < 100/MicroL (P < .045). Those variables included treatment with more than three antibiotics, treatment with more than three parenteral antibiotics, > 30 days of antibiotic treatment, bacterial infections, > 30 days in the hospital, hypoalbuminemia, C3 (Centers for Disease Control and Prevention) classification of HIV infection, and malnourishment. We conclude that prolonged placement of central venous catheters is the most important risk factors for fungemia in HIV-infected children and that the risk of fungemia is further influenced by antibacterial therapy, catheter manipulation, and host response.

Pain in pediatric human immunodeficiency virus infection: incidence and characteristics in a single-institution pilot study.

OBJECTIVE: Children with human immunodeficiency virus (HIV) infection have multiple complications associated with the disease process. Many of these complications are potentially painful and could affect the patient's quality of life. We examined the incidence and characteristics of the perception of pain in a cohort of families with children with HIV infection. METHODOLOGY: A questionnaire was developed and validated with a cohort of families with children with cancer. In a survey of families at the Pediatric Branch of the National Cancer Institute, 61 children with HIV infection and their care givers, along with 19 children with cancer and their care givers, were interviewed to determine the incidence and impact of pain. RESULTS: Fifty-nine percent of the HIV-infected children and 55% of their care givers described pain as a component of their illness that impacted on their lives. Younger children and girls tended to report more pain. There was also a tendency for biological parents to expect and to treat more pain than foster parents, although there was no difference in the incidence of pain that biological and foster parents reported for their children. No differences were found between parents who were HIV positive and those who were not. In addition, no correlations were noted in incidence, expectation, or impact of pain with disease progression or surrogate markers such as CD4 counts. Pain in HIV-infected patients tended to be either in the gastrointestinal tract or limbs and usually responded to nonsteroidal anti-inflammatory therapy. The patients with cancer reported an incidence (47%) and impact of pain similar to those of previously reported studies on pediatric patients with cancer. CONCLUSION: Pain is common among children infected with HIV and can adversely impact on their lives, and its management should be a component of the general care of these patients.

Bone marrow aspirates and biopsies in children with human immunodeficiency virus infection.

PURPOSE: Hematopoietic abnormalities are common in patients infected with the human immunodeficiency virus (HIV). We evaluated the role of diagnostic bone marrow aspirations and biopsies in HIV-infected children. METHODS: Seventy-eight bone marrow biopsies and aspirates performed during the last 8 years at the Pediatric Branch of the National Cancer Institute from 60 children with symptomatic HIV infection were reviewed retrospectively. The results were correlated with clinical stage, use of antiretroviral therapy or hematopoietic growth factors, and hematopoietic parameters. RESULTS: Most patients (84%) showed a normal or hypercellular marrow, associated with diffuse lymphocytosis (50%) or therapy with hematopoietic growth factors (33%). Dyspoietic features were very common in all three cell lineages. Twenty-seven (44%) of the patients had decreased iron stores in the bone marrow that correlated with iron deficiency as documented by serum tests in more than one-third of our study population. Bone marrow cultures were not more helpful than peripheral cultures in establishing the diagnosis of an opportunistic infection. CONCLUSION: Although bone marrow abnormalities are very common in HIV-infected children, they are rarely specific. The role of diagnostic bone marrow aspirates and biopsies appears to be limited, and this invasive procedure should be reserved for specific situations (e.g., to rule out a malignancy).