Effect of an intervention to reduce procedural pain and distress for children with HIV infection.

OBJECTIVE: To evaluate a multicomponent pain management intervention, including cognitive behavioral strategies, for children with human immunodeficiency virus (HIV) infection undergoing routine venipuncture. METHODS: Following a baseline venipuncture, children were exposed to an intervention including preparation, relaxation, distraction, reinforcement, parent involvement, and EMLA (eutectic mixture of local anesthetics) cream, and followed for three additional venipuncture procedures. After each procedure, child distress was rated on the Procedure Behavior Checklist (PBCL), child self-report of pain was obtained using the FACES scale, and parent anxiety was reported on the State Trait Anxiety Inventory-State Scale (STAI). RESULTS: Significant reductions in child distress and pain were found by the second postintervention procedure and maintained at the third. Parent anxiety was significantly reduced by the second postintervention procedure, but many parents chose not to participate in the third postintervention procedure. CONCLUSIONS: With repeated exposure, a multicomponent pain management intervention, including cognitive behavioral strategies and EMLA, appears effective at reducing pain, distress, and parent anxiety for children with HIV.

Survival in children with perinatal HIV infection and very low CD4 lymphocyte counts.

OBJECTIVES: To evaluate clinical conditions associated with mortality in HIV-infected children with CD4+ counts <100 cells/microl. METHODS: The Pediatric Spectrum of HIV Disease Project is a longitudinal medical record review study with eight study sites in the United States, which have been enrolling children since 1989. Survival time from baseline very low CD4 count (<100 cells/microl) to death was estimated using the Kaplan-Meier method. Cox proportional hazards models were used to evaluate the effect of clinical variables on mortality. RESULTS: Of 522 children (>/=1 year of age) with serial CD4+ T-lymphocyte measurements, the median age at the first very low CD4 count was 4.8 years. The estimated median survival following the first very low CD4 count was 36 months. The following factors present at the first very low CD4 count were independently associated with a higher risk of death: younger age, weight-for-age >2 standard deviations below the mean, and previously diagnosed AIDS. The subsequent development of cytomegalovirus (CMV)-associated disease, Mycobacterium avium intracellulare (MAI) infection, wasting syndrome, or esophageal candidiasis was also independently associated with a higher risk of death. CONCLUSION: Survival in HIV-infected children with very low CD4 counts before introduction of highly active antiretroviral therapy was highly variable. Poor nutritional status and the development of CMV disease or MAI infection were associated with the shortest survival times.

Lack of definitive severe mitochondrial signs and symptoms among deceased HIV-uninfected and HIV-indeterminate children < or = 5 years of age, Pediatric Spectrum of HIV Disease project (PSD), USA.

BACKGROUND: In response to recent reports of mitochondrial dysfunction in HIV-uninfected infants exposed to antiretroviral (ARV) prophylaxis, the Perinatal Safety Review Working Group reviewed deaths in five large HIV-exposed perinatal cohorts in the United States to determine if similar cases of severe mitochondrial toxicity could be detected. We describe the results of this review for the PSD cohort. METHODS: Hospitalization, clinic and death records for deceased HIV-uninfected and HIV-indeterminate children who were less than 5 years of age were reviewed. Standard definitions were used to classify HIV infection status and the likelihood that signs and symptoms were related to mitochondrial dysfunction. Children were classified as having signs and symptoms that were considered (1) unrelated, (2) unlikely, (3) consistent with, or (4) likely related to mitochondrial disease. SIDS deaths were put into a separate category. RESULTS: 8,465 of 13,125 HIV-exposed children were either HIV-uninfected or HIV-indeterminate. Among the 84 deaths in the subgroup of 8,465 children, 9 were considered in Class 2 (unlikely), 4 were considered in Class 3 (consistent with), and none were considered in Class 4 (likely). 97% of those children who received ARV prophylaxis received zidovudine alone. None of the HIV-uninfected deaths were classified in 2, 3, or 4; and only one of these was exposed to ARV prophylaxis. Among the 3 HIV-indeterminate children who were classified in 3 (consistent with), 2 had no or unknown ARV exposure before 1994 when use of ZDV prophylaxis became the standard of care. Both HIV-uninfected and HIV-indeterminate children with ARV exposure or unknown exposure had lower mortality rates than children without ARV exposure. CONCLUSION: Monoprophylaxis with ZDV was not associated with higher death rates in the cohort of 8,465 children or with any findings likely consistent with mitochondrial dysfunction among the 85 deaths. Ongoing monitoring of drug safety in large multi-site prospective cohort studies of HIV-exposed children is essential in the era of highly active antiretroviral therapy.

Human immunodeficiency virus-infected adolescents: a descriptive study of older children in New York City, Los Angeles County, Massachusetts and Washington, DC.

BACKGROUND: Children infected with HIV are entering adolescence with challenging and changing medical and social needs. Through chart review we describe certain medical and social characteristics of adolescents who acquired HIV as children. METHODS: HIV-infected children 12 years of age and older in 1995 were monitored through the Pediatric Spectrum of HIV Disease study from four US sites. In addition to standard 6-month medical chart reviews, a special chart abstraction in 1997 collected available psychosocial and sexual history information. RESULTS: A total of 131 adolescents HIV-infected as children were studied: 52 infected perinatally; 44 infected through a contaminated blood transfusion; 30 through receipt of contaminated blood products for hemophilia; and 5 with unknown transmission mode. Mean age at last medical contact was 15.5 years, 67% were Hispanic or African-American, 12% were employed, 66% attended regular school, 66% knew their HIV status and 48% (8% for the perinatally infected) lived with their biologic mother. Information on sexual activity showed that 18% had sexual relations, 28% did not and for 53% sexual activity was not recorded in the medical chart. Four percent used illicit drugs, which along with sexual activity showed a positive association with age. Forty-two percent had an AIDS-defining opportunistic infection, and 56% had a recent CD4+ lymphocyte count <200 cells/microl. CONCLUSIONS: Adolescents in this study represent a heterogeneous group of surviving HIV-infected children some of whom are sexually active and potential sources of HIV transmission. Clinicians who treat HIV-infected and high risk adolescents face the challenges of providing care and prevention services appropriate to adolescent development.

Basic fibroblast growth factor in HIV-associated hemolytic uremic syndrome.

Endothelial injury is the primary pathogenic event leading to the renal thrombotic microangiopathic lesions typical of the hemolytic uremic syndrome (HUS). Basic fibroblast growth factor (bFGF) is an angiogenic growth factor released by injured endothelial cells. In a previous study we have found a significant accumulation of bFGF in human immunodeficiency virus (HIV)-transgenic mice with renal disease. Here we investigated whether bFGF was accumulated in the circulation and kidneys of two children with HIV-associated HUS (HIV-HUS), and studied the mechanisms involved in this process. The plasma levels of bFGF in children with HIV-HUS (124+/-20 pg/ml) were increased compared with five children with HIV nephropathy (49+/-6 pg/ml) and twenty HIV-infected children without renal disease (26+/-4 pg/ml, P<0.001). Immunohistochemistry and receptor binding studies showed that bFGF was accumulated bound to heparan sulfate proteoglycans in renal glomeruli and interstitium surrounding renal tubules in HIV-HUS kidneys. Basic FGF stimulated the proliferation of mesangial and urinary renal tubular epithelial cells isolated from both patients. These findings support the hypothesis that bFGF and its low-affinity binding sites may play a relevant role in modulating the process of glomerular and renal tubular regeneration during the acute stages of HIV-HUS. A follow-up study in a larger sample population is required to confirm these results.

Thrombopoietin levels in HIV-associated thrombocytopenia in children.

OBJECTIVES: To determine the mechanism of human immunodeficiency virus (HIV)-associated thrombocytopenia by using thrombopoietin (TPO) levels. STUDY DESIGN: TPO levels were measured in 14 HIV+ children with thrombocytopenia (TCP+), 28 HIV+ children without thrombocytopenia (TCP-), and 15 matched control subjects. RESULTS: For the patients with moderate symptoms, TPO levels were similar for the TCP+ and TCP- groups (251 pg/mL vs 263 pg/mL; P =.98) and similar to those of control subjects. For the patients with severe symptoms, TPO levels were significantly higher for the TCP+ group versus the TCP- group (1172 pg/mL vs 222 pg/mL; P =.03). Patients with severe symptoms and thrombocytopenia had significantly higher TPO levels than those with moderate symptoms and thrombocytopenia (P <.005), were more likely to require growth factors, and did not respond to treatment with intravenous immunoglobulin. CONCLUSIONS: TPO levels can distinguish 2 groups of patients with HIV-associated thrombocytopenia. Patients with severe disease had elevated TPO levels, did not respond to treatment with intravenous immunoglobulin, and were more likely to be growth factor-dependent, suggesting marrow failure.

Human immunodeficiency virus (HIV)-associated nephropathy in children from the Washington, D.C. area: 12 years' experience.

Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is a clinicopathologic entity that includes proteinuria, azotemia, focal segmental glomerulosclerosis or mesangial hyperplasia, and tubulointerstitial disease. The incidence of HIVAN is increased in black patients and variable depending on the age and geographic area. The objective of this study was to describe relevant clinical and pathological findings in 30 children with HIVAN followed at the Children's National Medical Center in Washington, D.C. Our experience of the last 12 years showed a spectrum of HIVAN that seems to be coincident with the degree of acquired immunodeficiency syndrome (AIDS) symptomatology. By renal sonograms and frequent urinalysis, we identified children undergoing the early stages of HIVAN with enlarged echogenic kidneys, proteinuria, and "urine microcysts". HIVAN did not necessarily progress rapidly to end-stage renal disease. Nephrotic syndrome or chronic renal insufficiency were late manifestations of HIVAN. Children with HIVAN were likely to develop transient electrolyte disorders, heavy proteinuria, and acute renal failure due to systemic infectious episodes or nephrotoxic drugs. HIVAN was associated with other HIV-induced illnesses and high mortality rates. Early detection and careful clinical follow-up of children with HIVAN may reduce the incidence of renal-cardiovascular complications and improve their quality of life.

Streptococcus pneumoniae bacteremia in children infected with HIV: presentation, course, and outcome.

OBJECTIVE: To examine the presentation, course, and outcome of pneumococcal bacteremia in children infected with human immunodeficiency virus (HIV). METHODS: A retrospective series of HIV-infected children less than 18 years of age with Streptococcus pneumoniae bacteremia from four urban, tertiary care hospitals was evaluated. The main outcome measures included persistent bacteremia, the development of a focal infection, and death. RESULTS: Seventy-two episodes of pneumococcal bacteremia were identified in 59 patients. Fifty-four first episodes were included; 26/54 were occult. Mean temperature was 39.8 degrees C. In patients with bacteremia, white blood cells (WBCs) > or = 15,000 and > or = 10,000 had sensitivities of 40% and 75%, respectively. At the time of bacteremia, age >3 years old was associated with a lower mean WBC count compared with episodes occurring in patients <3 years old (11.2 vs 16.1, P < 0.05). Patients with occult bacteremia who were discharged with antibiotics (12 i.m., 7 p.o.) were less likely than patients without antibiotic treatment to have persistent bacteremia at a return visit within 72 hours (0/19 vs 2/5, P < 0.05). No patient with occult bacteremia died, progressed to clinical meningitis, or had other sequelae. Two of fifty-four patients died as a result of their first episode of invasive pneumococcal disease. Both patients who died had meningitis and appeared ill on initial presentation. CONCLUSIONS: Neither a WBC count > or = 15,000 nor > or = 10,000 is a sensitive indicator of pneumococcal bacteremia in HIV-infected children. Empiric antibiotics are useful to decrease the risk of persistent bacteremia. Children infected with HIV who have occult pneumococcal bacteremia appear to do well with appropriate antibiotics. Patients who are afebrile and well appearing on reevaluation may be safely treated as outpatients.

Amebic osteomyelitis in a child with acquired immunodeficiency syndrome: a case report.

Disseminated Acanthamoeba infection has been described in immunocompromised or debilitated patients. The usual sites of involvement are skin, sinus, and brain. Sporadic reports of Acanthamoeba infection in patients infected with the human immunodeficiency virus are present in recent literature, predominantly in adults, and one case involving an 8-year-old child. We describe a case of amebic osteomyelitis, seen in a 6-year-old child with vertically acquired human immunodeficiency virus and a 6-month history of cutaneous Acanthamoeba infection.

Epstein-Barr virus DNA in the blood of infants, young children, and adults by age and HIV status.

Polymerase chain reaction (PCR) methodology was used to detect Epstein-Barr virus (EBV) DNA in peripheral blood mononuclear cells (PBMCs) from children and adults whose HIV status (i.e., infected or uninfected) is known. Initial EBV infections especially occurred in children between the ages of 7 and 24 months. EBV-positive children with vertically acquired HIV infection tended to have a detectable blood level of EBV DNA for a period of years, and their EBV DNA blood levels often exceeded 10,000 copies/0.1 ml of blood--hundreds of times higher than levels typically found in EBV-positive, HIV-uninfected children of the same age. EBV DNA was found in PBMCs in 26% of 49 HIV-infected mothers who were sampled during their pregnancy, but the median EBV DNA level in their EBV-positive samples was low--only 50 copies/0.1 ml blood. In limited tests with specimens from children infected with both HIV and EBV, high blood levels of EBV DNA unexpectedly appeared to be associated with decreased blood levels of HIV DNA (p = .063).

A typical hemolytic uremic syndrome in human immunodeficiency virus-1-infected children.

We describe the clinical and pathological findings of the hemolytic uremic syndrome (HUS) in two children with human immunodeficiency virus (HIV) infection. Both patients presented with microangiopathic hemolytic anemia, thrombocytopenia, and subsequently developed renal failure. The diagnosis of HUS was confirmed by renal histopathology in both patients. None of these children presented with bloody diarrhea, evidence of circulating antibody response to Escherichia coli O157 lipopolysaccharide, or other known risk factors for HUS, except for the presence of HIV infection. Each patient was treated with intravenous plasma infusion and renal replacement therapy. Their clinical course was characterized by non-oliguria and lack of significant hypertension throughout the acute phase of the disease. Despite these favorable clinical parameters, both patients developed end-stage renal failure. The etiology of this atypical HUS characterized by poor renal survival remains unknown and the role of HIV infection in its pathogenesis, although possible, is unclear.

HIV DNA blood levels in vertically infected pediatric patients: variations with age, association with disease progression, and comparison with blood levels in infected mothers.

Blood levels of HIV DNA in our vertically infected pediatric patients typically followed a characteristic age-related pattern: continuously increasing with increasing age to a peak between ages 4 and 8 months, and thereafter rather steadily declining. Median HIV DNA levels peaked about 3 months earlier in children who by age 24 months developed more severe rather than less severe HIV disease. Children at particular risk of developing severe HIV disease by age 24 months commonly had > 800 HIV DNA copies per 0.1 ml of blood at age 3 weeks to 2 months, > 1,000 copies at 2 to 4 months, and > 2,500 copies at ages 4 to 6 months. Near the time of delivery mothers who transmitted HIV had significantly higher median blood levels of HIV DNA than mothers who did not transmit, but median HIV DNA levels in infected mothers as a group were low compared with those in pediatric patients > or = 1 month of age.

Viral studies of mothers with human immunodeficiency virus infection at delivery and their infants in the first 3 days of life.

OBJECTIVE: We studied 49 mother-infant pairs for human immunodeficiency virus (HIV) (a) to assess the virological and immunological status of HIV-infected mothers at delivery and their infants within the first 3 days of the infant's life, and (b) to correlate these findings with eventual infection outcome in the infant. METHOD: Maternal blood from women in labor and infant's blood within 3 days of life were tested for the titer of HIV immunoglobulin G (IgG) antibody, for presence of HIV by culture, for p24 antigen, for HIV DNA by polymerase chain reaction (PCR), and for absolute T-helper cell count (CD4). RESULTS: Eight infants were in the confirmed infected (CI) group, with a transmission rate of 21%. Thirty infants were in the confirmed uninfected (CU) group. In the mother, mean anti-HIV IgG titer was 1:2600 (CI group) and 1:3350 (CU group); in the infant, the mean titer was 1:3250 (CI group) and 1:2710 (CU group). Eighty-seven percent of the mothers were culture-positive in the CI group compared to 33% in the CU group (p = 0.005). Eighty-seven percent of CI infants were PCR-positive at birth; none was PCR-positive in the CU group (sensitivity = 87%; specificity = 100%). Sixty-two percent of CI infants were culture-positive at birth, whereas none was positive in the CU group (sensitivity = 62%; specificity = 100%). Of the uninfected infants, 23% were positive for p24 antigen at birth. CONCLUSIONS: HIV IgG antibody titers in mothers and their infants at birth were markedly elevated in both CI and CU groups but were not protective against infection. However, the high titers explain the long duration of this antibody in the blood of infants born to infected mothers. Culture positivity in the mother at delivery correlated highly with eventual infection in the infant (p = 0.005). HIV antigen, specifically p24 antigen, was detectable in uninfected infants when tested at birth.

HIV antibody responses in children of HIV-infected mothers.

About 25% of the children of untreated HIV-infected mothers are later determined to be HIV-infected. At birth, all of the children of HIV-infected mothers have HIV-IgG antibody, which is transferred transplacentally from the mothers to their children, and infected children produce HIV-IgG antibody in response to their infection. Most infected children have detectable HIV-IgA by 3 months of age. We have studied HIV antibody responses in three groups of children of HIV-infected mothers at 9 to 12 months and 15 to 24 months of age. The groups were classified by Centers for Disease Control and Prevention (CDC) criteria and included: (I) HIV seroreverters (SR); (II) HIV-infected; Non- to mildly symptomatic (N+A); and (III) HIV-infected; Moderately to Severely Symptomatic (B+C). HIV-IgG antibody was detected in some SR children at low titer levels (10 to 20) through 11 months of age but not at 12 or later. For both the N+A and B+C groups, there were no significant changes in the mean HIV-IgG titers from 9-12 to 15-24 months of age. Also, no significant difference in titers were found between the two infected groups for both age groups. HIV-IgA antibody responses were more frequently positive at 15 to 24 months for all seven antigens studied for the N+A than the B+C patients; however, statistical significance was attained only for gp41 (p < or = 0.01). N+A children showed more responses to the viral antigens at 15-24 months than at 9-12 months. This increase in HIV-specific IgA among the N+A children may be important in restricting their HIV infections. Total IgG levels were significantly higher in the HIV-infected groups than in the SR (p < or = 0.0001), but no differences were detected between the N+A and B+C groups. Total IgA increased over time in the N+A patients from 9-12 to 15-24 months. A similar trend was apparent in the B+C group, but did not reach statistical significance. Both N+A and B+C patients at 15-24 months had significantly higher total IgA levels than did the SR at 9-12 months of age. The B+C group had significantly lower CD4 counts for both age groups than did the N+A or SR groups (p < or = 0.0001).

Coinfection with herpesviruses in young children of HIV-infected women.

Coinfection with herpesviruses in young children born to human immunodeficiency virus (HIV)-infected women was studied with blood samples from children who were 9-12 months and 15-24 months of age. Three groups of children were included: (I) HIV-uninfected, asymptomatic (HIV-); (II) polymerase chain reaction (PCR) and/or culture-positive and asymptomatic or mildly symptomatic (HIV+ asymptomatic); and (III) PCR and/or culture-positive and symptomatic (HIV+ symptomatic). Significantly more of the HIV+ symptomatic patients had cytomegalovirus (CMV) antibody than the HIV patients. In addition, CMV antibody levels were significantly higher in the HIV+ symptomatic patients than in either of the other two groups. Human herpesvirus 7 (HHV-7) antibody titers were significantly different among the three groups of patients; however, no pairwise comparisons were significant. No differences were found for HHV-6 or Epstein-Barr virus (EBV) antibody frequencies or titers. These findings suggest that infection with CMV is a cofactor or an opportunistic infection causing symptomatic HIV infections in young children.

Spectrum of chest radiographic abnormalities in children with AIDS and Pneumocystis carinii pneumonia.

This report aims to provide a description of the spectrum of radiographic findings in children with AIDS and Pneumocystis carinii pneumonia (PCP). The chest radiographs of all children with perinatally transmitted HIV infection who had PCP were reviewed. Thirty-eight episodes of PCP were noted in 32 children. The age range was 2-17 months. The radiographic findings were characterized as to pattern, severity, presence of pulmonary air cyst, thoracic air leak, thoracic lymphadenopathy, and pleural effusion. The initial distribution of disease was as follows: diffuse (n = 20), patchy (n = 12), focal (n = 4), normal (n = 2). In nearly one-third of children parenchymal abnormalities were mild enough that most normal lung markings were visible. During the course of the illness pneumothorax was noted in eight cases, pulmonary air cyst in five, and pneumomediastinum in one. Pleural effusions were noted in three (5%) cases. Thoracic lymphadenopathy was not observed in any case. The authors concluded that the initial chest radiographic appearance of PCP in children with AIDS is variable. The initial chest radiograph may be normal. The distribution was patchy or focal in nearly one-half of all cases with parenchymal abnormalities. Pulmonary air cysts or thoracic air leaks were noted during the course of the illness in approximately one-third of all cases.

Abdominal lymphadenopathy in children with AIDS.

PURPOSE: To identify conditions associated with abdominal lymphadenopathy in children with vertically-transmitted human immunodeficiency virus (HIV) infection. METHODS: Abdominal computed tomography (CT) scans were performed on 29 children over an eight-year period. The presence or absence of abdominal lymphadenopathy (> 10 mm in diameter) was prospectively evaluated at the time of CT. Clinical and histopathologic data in these children was reviewed. RESULTS: Abdominal lymphadenopathy was noted in eight (28%) children. The lymphadenopathy was isoattenuating relative to adjacent muscle in all cases. The most common specific associated diagnosis was systemic infection with Mycobacterium avium intracellulare (three children). One child had disseminated Kaposi sarcoma while four children had no known associated systemic infection or neoplasm. CONCLUSIONS: Abdominal lymphadenopathy was noted at CT in 28% of all HIV-infected children studied with CT and represented a nonspecific finding. The presence of lymphadenopathy should raise the suspicion of disseminated mycobacterial infection; however, it may also be observed in the absence of known systemic infection or neoplasm.

Hepatobiliary abnormalities on sonography in children with HIV infection.

Our purpose was to characterize the spectrum of hepatobiliary abnormalities on sonography in children with vertically transmitted HIV infection. Abdominal sonograms were performed on 41 children with HIV infection and correlated with clinical and histopathologic data. Hepatobiliary abnormalities were noted in 26 (63%) children. Hepatomegaly (n = 13) and abnormal hepatic echotexture (n = 13) were the most common abnormalities noted. Preexisting AIDS-related infections or neoplasms were noted significantly more frequently in children with hepatic or biliary abnormalities on sonography (18/26, 69%) than in children without abnormalities (5/15, 33%) (P = 0.0001). Most children with hepatobiliary abnormalities on sonography who underwent hepatic tissue sampling, however, did not have evidence of acute infection or neoplasia. Hepatobiliary abnormalities are frequently noted on sonography in children with HIV infection. Hepatomegaly and abnormal hepatic echotexture are the most frequent sonographic findings and are usually nonspecific.

Human immunodeficiency virus infection in infants during the first 2 months of life. Reliable detection and evidence of in utero transmission.

OBJECTIVE: To evaluate the clinical utility of a polymerase chain reaction (PCR) method for detecting human immunodeficiency virus (HIV) infection in infants 2 months of age or younger who were born to HIV-positive mothers. DESIGN: Prospective, longitudinal study lasting 3 years. The PCR tests were performed with coded peripheral blood mononuclear cell lysates, and results were compared with findings using Centers for Disease Control and Prevention (CDC) (Atlanta, Ga) criteria defining HIV infection in children. SETTING: Hospitals, particularly a pediatric hospital in Washington, DC. PATIENTS: Newborns, young infants, and HIV-infected mothers. OUTCOME MEASURE: Presence or absence of pediatric HIV infection using CDC criteria compared with a diagnosis based on the detected presence or absence of HIV proviral DNA using PCR testing. RESULTS: One or more blood samples obtained by 62 days of age from 30 (94%) of 32 HIV-infected infants were positive for HIV by routine PCR testing. Blood samples from 32 infants now confirmed to be uninfected tested negative for HIV. Human immunodeficiency virus DNA was detected in blood samples obtained within 48 hours of birth from eight of nine infected infants. In six of these newborns as well as most older infants, HIV DNA was present in such quantity that it was detectable in specimens equivalent to 0.01 mL or less of the original blood sample. CONCLUSIONS: Our PCR procedure can reliably detect the presence or absence of HIV infection during the first 2 months of life. The frequent presence and not uncommon high titer of HIV DNA within 48 hours of birth suggest that much of the transmission of HIV from mother to infant occurs well before birth.