Serum immunoglobulin G subclasses in children infected with human immunodeficiency virus type 1

We studied serum concentrations of IgG subclasses in 47 human immunodeficiency virus 1-infected (17 asymptomatic and 30 symptomatic) children. Thirty-nine of 47 (83%) had an abnormality of at least 1 subclass. Sixteen had only elevated IgG1, 6 had only elevated IgG3 and 12 had elevated IgG1 and IgG3 concentrations. IgG2, IgG4 and combined IgG2-IgG4 deficiency was found in 3, 4 and 4 patients, respectively. IgG2 concentrations did not differ between patients with (n = 23) or without (n = 24) bacterial infections. Additionally the number of bacterial infections was similar between the patients with normal or low IgG2 and/or low IgG4. These data indicate that IgG subclass abnormalities are found in most children with human immunodeficiency virus 1 infection, but quantitative deficiencies of specific subclasses do not appear to explain the high frequency of bacterial infections occurring in these patients.     

Helper T-cell responses in children infected with human immunodeficiency virus type 1.

Helper T-cell function was evaluated in 34 children infected with human immunodeficiency virus type 1, by assessing interleukin-2 production after stimulation of peripheral blood mononuclear cells with recall antigens (influenza virus, tetanus toxoid), allogeneic HLA, and phytohemagglutinin. In addition, helper T-cell function was correlated retrospectively with the incidence of opportunistic and bacterial infections. Four patterns of helper T-cell function were observed: (1) 7 (21%) of the 34 children responded to all stimuli, (2) 7 (21%) of them responded to alloantigens and phytohemagglutinin but not to recall antigens, (3) 7 (21%) responded to phytohemagglutinin but not to recall antigens or alloantigens, and (4) 13 (37%) did not respond to any of these stimuli. There were no significant differences related to different routes of acquisition among patients. Patients with functional helper T-cell defects had a history of more opportunistic (p = 0.03) and bacterial (p less than 0.001) infections than did patients with intact helper T-cell function. Thus distinct patterns of helper T-cell dysfunction exist in children infected with human immunodeficiency virus type 1 and correlate with higher frequency of infections. Comparisons of in vitro helper T-cell responses to these stimuli may be useful for detecting early functional helper T-cell defects and for monitoring progression of disease.     

Varicella-zoster virus infections in children infected with human immunodeficiency virus

Primary varicella-zoster (VZ) infection in eight children with perinatally acquired human immunodeficiency virus infection tended to be severe, prolonged, complicated by bacterial infections and in one case fatal. Depletion of CD4-lymphocytes was associated with chronic and recurrent VZ infection. In some patients convalescent VZ antibody titers were low and did not correlate with recurrence of VZ lesions. Administration of acyclovir appeared to be beneficial in suppressing VZ in human immunodeficiency virus-infected children with primary or recurrent VZ infection.     

Longitudinal antiretroviral adherence among adolescents infected with human immunodeficiency virus

OBJECTIVES: To longitudinally follow a cohort of adolescents with human immunodeficiency virus (HIV) and to investigate long-term antiretroviral therapy adherence and factors associated with adherence. DESIGN, SETTING, AND PATIENTS: Adolescents infected with HIV (N = 231; mean age, 18.4 years; 72.7% female; 74.9% African American) from 13 cities throughout the United States were assessed at 3-month intervals. MAIN OUTCOME MEASURES: Self-reported adherence measures were validated by comparison with HIV-1 RNA viral load, and behavioral factors that may be associated with antiretroviral therapy adherence were assessed. RESULTS: At the initial visit, approximately 69% of the adolescents reported being adherent to antiretroviral therapy. Adolescents in the later HIV disease stage were less likely to be adherent compared with those in the earlier disease stage. Less alcohol use and being in school were associated with adherence by adolescents on weekends and over the preceding month. Longitudinal adherence was investigated among 65 subjects initially adherent with available information for at least 4 consecutive visits. The median time to nonadherence was 12 months, and failure to maintain adherence was significantly associated with younger age and depression. Among adolescents who attained an undetectable viral load, only about 50% maintained an undetectable viral load for the year. CONCLUSIONS: These findings indicate an urgent need for better interventions to assist adolescents with HIV in adhering to their medication regimens. Adolescents with advanced disease are likely to need more intervention. New treatments recently found effective for adolescent depression may assist in improving adherence for a majority of adolescents with HIV.     

Deficient human immunodeficiency virus type 1-specific cytotoxic T cell responses in vertically infected children

Cytotoxic T lymphocyte (CTL) responses to human immunodeficiency virus type 1 (HIV-1) gag proteins were studied prospectively in 17 children (12 infected) born of mothers with HIV-1 seropositivity and in five pediatric patients with hemophilia infected by transfusion of HIV-1-contaminated factor VIII concentrate. B lymphoblastoid cells infected with vaccinia virus vectors expressing HIV-1 gag gene products were combined with autologous peripheral blood mononuclear cells to detect circulating CTLs. Effector cells were defined by monoclonal antibody-mediated, complement-dependent cytolysis. Circulating HIV-1 gag-specific cytotoxic responses were detectable in 4 of 5 HIV-1-infected pediatric hemophilic patients, and were similar in magnitude to those previously described in adults. In contrast, circulating HIV-1 gag-specific cytolysis was detectible in only 3 of 12 vertically infected children. Depletion data revealed that the majority of detectible gag-specific cytolysis was CD8 T cell-mediated. No apparent relationships between CD4 T cell counts, CD8 T cells counts, or serum p24 antigen levels and CTL responses were seen. Deficient CTL development may, in part, explain the more rapid onset of symptomatic disease following vertical HIV infection.     

Neuropsychological functioning in human immunodeficiency virus type 1 seropositive children infected through neonatal blood transfusion

The neuropsychological development of 15 human immunodeficiency virus type 1 (HIV-1) seropositive children infected through neonatal blood transfusion was compared with that of a control group of 33 HIV-1 seronegative children who had also received blood transfusions as neonates. Human immunodeficiency virus type 1 infection was identified on the basis of a callback blood testing. Two thirds of the HIV-1-infected children were asymptomatic at time of enrollment in the study of development. The children were administered two psychological batteries approximately 8 months apart. The results indicated that the two serostatus groups did not differ in overall intelligence, even as long as 8 years after HIV-1 infection. Significant group differences, though slight, were found on school achievement and on tasks that require motor speed, visual scanning, and cognitive flexibility. Continued longitudinal study of this cohort will be important in characterizing the evolution of neuropsychological deficits.     

Occurrence of infections in children infected with human immunodeficiency virus

To evaluate the occurrence of infections in asymptomatic and symptomatic human immunodeficiency virus (HIV)-infected children we performed a prospective comparative cohort study. Twenty-seven HIV-infected children were individually matched with paired immunocompetent controls and followed up for a total of 543 months (mean per child, 19.4 +/- 11 months). Collected data were evaluated considering HIV-infected children both as a whole and as P1 and P2 patients according to the Centers for Disease Control classification. Twenty-seven HIV-infected children had 185 infectious episodes vs. 27 matched controls who experienced 118 infections. P1 children had a number of infections similar to those of normal controls (99 vs. 86) whereas P2 children had a significantly higher number of infections than did controls (86 vs. 32). Pneumonia and oral candidiasis occurred significantly more frequently in symptomatic HIV-infected children than in normal controls. Severe infections occurred almost exclusively in HIV-infected symptomatic children.     

Neurologic manifestations of human immunodeficiency virus infection in children

This report describes the neurologic manifestations of 36 children with human immunodeficiency virus (HIV) infection. In this cohort, in 16 of 21 children with acquired immunodeficiency syndrome (AIDS), three of 12 children with AIDS-related complex, and one of three asymptomatic seropositive children, a progressive encephalopathy developed. Neurologic signs were often detected early but tended to worsen coincident with progression of the immunodeficiency. The presence of progressive encephalopathy correlated with the absence of serum neutralizing antibodies to HIV and with a poor, usually fatal, outcome. The incubation period from initial HIV infection in the perinatal period to the onset of progressive encephalopathy varied from 2 months to 5 years. Intrablood-brain barrier synthesis of HIV-specific antibodies was demonstrated in eight of 14 children with AIDS and AIDS-related complex, indicating active brain infection with HIV. In three cases this was unassociated with progressive neurologic signs. Unique neuropathologic findings in children who died with HIV infection further suggest that the progressive encephalopathy is the result of primary and persistent infection of the brain with this retrovirus. These findings broaden the spectrum of HIV infection in children and have important implications for the development of antiviral therapy.     

Meningoencephalitis in a neonate congenitally infected with human immunodeficiency virus type 1.

A newborn infant born to a mother infected with human immunodeficiency virus type 1 had acute meningoencephalitis on the second day of life. Human immunodeficiency virus type 1 was isolated from the plasma, cerebrospinal fluid, and peripheral blood mononuclear cells. Specific IgM for human immunodeficiency virus type 1 was detected by an enzyme-linked immunosorbent assay antibody-capture technique in cord blood and in serum obtained 3 weeks later. We believe that the meningoencephalitis was caused by human immunodeficiency virus type 1 acquired in utero.     

Endocrine function in thai children infected with human immunodeficiency virus

Most children infected by HIV show manifestations which mimic the clinical features of endocrine dysfunction, such as failure to thrive and hyperpigmentation. Our cross-sectional study was designed to assess the endocrine function of Thai children infected with HIV and to determine any relationship between disease severity, height and endocrine function. Thirty-six prepubertal children infected by HIV, 12 boys and 24 girls, aged 4-12 years (mean +/- SD 7 +/- 2 years), were tested for thyroid function (serum T4, T3, TSH and free T4), morning serum cortisol level, serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3). Disease severity was assessed using CD4+ T-lymphocyte percentage. Ten (28%) patients showed abnormal thyroid function. Five patients had euthyroid sick syndrome. Thyroid function tests indicated another five patients had a condition compatible with compensated hypothyroidism. Most patients had normal morning serum cortisol levels. Two-thirds and one-third of the patients showed low IGF-I and IGFBP-3 standard deviation scores (SDS), respectively. Twenty-six (72%) patients had CD4+ T-lymphocyte <15%, thus were classified as severely immune suppressed. A weak linear relationship was indicated between disease severity and endocrine function (r = -0.03 to 0.41). Statistical significance was found between CD4+ percentage and IGF-I SDS, IGFBP-3 SDS, serum T3 and free T4 (p-value = 0.03, 0.02, 0.02 and 0.01, respectively. Nearly half (44%) the patients were below the third percentile for height of Thai children. There was also a weak correlation between height SDS and endocrine function (r = -0.03 to 0.41). Statistical significance was observed between height SDS and IGF-I SDS, serum T3 and TSH (p-value = 0.02 and 0.01, respectively). We conclude that HIV-infected children with demonstrated growth failure and greater disease severity tend to have abnormal endocrine function, particularly disordered IGF-I levels.     

Correction of antigen-specific T-lymphocyte function by recombinant cytokines in children infected with human immunodeficiency virus type 1.

To determine the role of cytokines in the immunodeficiency of children infected with human immunodeficiency virus type 1 (HIV-1), we compared the antigen-specific (tetanus toxoid-induced) T-lymphocyte blastogenesis of HIV-1-infected patients with and without the addition of exogenous interleukin-1 and interleukin-2. Acquisition of in vitro antigen-specific immunologic function was seen in some patients after the addition of exogenous cytokines. The antigen-specific immunodeficiency in some HIV-1-infected children is due to defects in cytokine production rather than to an absence of antigen-specific T lymphocytes.     

Altered bone metabolism in children infected with human immunodeficiency virus

Aim: Data on bone homoeostasis of children infected with human immunodeficiency virus (HIV), at the time of the gain in bone mass, are very rare. To determine possible alterations in bone metabolism, 13 prepubertal vertically HIV-infected children were studied. Methods: Viral load, CD4 count, interleukin-6 (IL-6), growth hormone, insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), acid-labile subunit (ALS), IGFBP-3 proteolysis, osteocalcin in blood and N-terminal telopeptide of type I collagen in urine were determined. Lumbar spine bone mineral density was examined by dual-energy X-ray absorptiometry. Results: Low osteocalcin levels were found in all patients. Low IGF-I was found in only six children, who had low CD4 count and high IL-6 levels, with normal levels of IGFBP-3 and ALS, absent IGFBP-3 proteolysis and decreased bone mineral density, irrespective of viral load or growth. Conclusion: Low serum osteocalcin levels appear to be an initial warning sign of possible altered bone metabolism in HIV-infected children. However, only when the immune system becomes more seriously compromised is bone loss measurable by bone densitometry.     

Mycobacterium tuberculosis in children with human immunodeficiency virus type 1 infection.

A retrospective study was conducted at the Childrens Hospital Center at Jackson Memorial Hospital in Miami, FL, to evaluate the natural history of Mycobacterium tuberculosis infection in nine children with vertically acquired human immunodeficiency virus type 1 infection. The patients' ages ranged from 6 months to 7 years (median age, 42 months). Common presenting symptoms included prolonged fever, cough and anorexia. Only one patient had a positive tuberculin test. Five patients evidenced only pulmonary disease, three patients had pulmonary and extrapulmonary disease and one patient developed extrapulmonary tuberculosis (mastoiditis) and pulmonary interstitial disease that could not be attributed to mycobacterial infection because of lack of information. Organisms isolated before January, 1989, were susceptible to isoniazid and rifampin whereas isolates from three patients cultured after that time were resistant to multiple antituberculosis drugs. The median survival time after M. tuberculosis diagnosis for all children was 20 months. Our study suggests that children with human immunodeficiency virus type 1 infection who have tuberculosis have an increased risk for extrapulmonary disease. A high index of suspicion for the diagnosis of M. tuberculosis should be maintained in human immunodeficiency virus type 1-infected children with prolonged fever and respiratory symptoms. In areas of high endemicity of multidrug-resistant organisms, therapy with a broader panel of drugs may need to be instituted until susceptibility testing becomes available.     

Clinical and endocrinologic manifestations in perinatally human immunodeficiency virus type 1--Infected children aged 5 years or older

Sixteen human immunodeficiency virus type 1 (HIV-1)-seropositive children aged 5 to 12 years (nine girls and seven boys), born to HIV-1-infected mothers, were diagnosed between 1984 and 1987 in Kigali, Rwanda. They were compared with a group of age- and sex-matched HIV-1-seronegative children consecutively selected from the outpatient department. Two subjects were asymptomatic. Chronic cough was the most frequent symptom (seven of 16 patients). The most common signs were short stature (12 of 16 patients), low weight for age (seven of 16 patients), chronic parotitis (eight of 16 patients), persistent generalized lymphadenopathy (seven of 16 patients), and pulmonary tuberculosis (four of 16 patients). Lymphoid interstitial pneumonitis was diagnosed on radiologic grounds in five of 16 patients. Evidence of perivasculitis in the fundus was noted in three of 16 patients. Two children died during the study period (mean duration of follow-up, 40 months; range, 27 to 62 months); none of the other children had life-threatening infection or loss of developmental milestones. Immunologic assessment in the 16 children revealed high levels of IgG, decreased CD4+/CD8+ ratio, and skin test anergy. Endocrinologic investigations revealed normal thyroid function and normal basal human growth hormone levels but low basal insulinlike growth factor I levels (0.21 +/- 0.07 vs 0.44 +/- 0.20 U/mL for controls). In Kigali, perinatally HIV-1-infected children surviving beyond 5 years of age often present with moderate signs and symptoms, principally pulmonary involvement, chronic parotitis, and persistent generalized lymphadenopathy. Short stature is the major clinical manifestation in these patients and may be due, in part, to low growth hormone secretion rather than to malnutrition.     

Cerebral artery aneurysms in children infected with human immunodeficiency virus.

More than 250 children treated at our institution on antiretroviral treatment protocols have been monitored with brain imaging studies. We documented the occurrence and progression of aneurysms of major cerebral arteries in two children with advanced human immunodeficiency virus infection. In both cases these lesions remained clinically silent initially, despite progression to marked dilation.