Trimethoprim-sulfamethoxazole oral desensitization in hemophiliacs infected with human immunodeficiency virus with a history of hypersensitivity reactions.

Hemophiliacs infected with human immunodeficiency virus with a history of hypersensitivity reaction to a combination product of trimethoprim and sulfamethoxazole were desensitized orally. Six of the seven patients included in the study successfully completed the desensitization protocol and received trimethoprim-sulfamethoxazole for 5 to 7 months after desensitization (mean length of treatment, 5.7 months) for prophylaxis of Pneumocystis carinii pneumonia. The small number of patients and the short follow-up allow us to suggest that oral desensitization may be an effective and inexpensive means to treat hemophiliacs infected with human immunodeficiency virus with trimethoprim-sulfamethoxazole as prophylaxis against Pneumocystis carinii pneumonia.     

Discontinuation of secondary prophylaxis for Pneumocystis pneumonia in human immunodeficiency virus-infected children treated with highly active antiretroviral therapy

This study shows the long term safety of discontinuing secondary prophylaxis for Pneumocystis pneumonia in 5 human immunodeficiency virus-infected children who had recovered from a confirmed episode of Pneumocystis pneumonia, had <15% of CD4 cells at the time of starting highly active antiretroviral therapy and whose CD4 cell counts increased to >15% for >or=3 months during highly active antiretroviral therapy.     

Bacterial infections in human immunodeficiency virus-infected children

A retrospective review of 71 children infected with human immunodeficiency virus cared for over a 3.5-year period revealed that 44 of 71 (63%) required a bacterial culture and 27 of 71 (37%) had bacteriologically documented infection. There were 125 episodes in 27 patients. Pneumonia (24 of 125 (19%)), upper respiratory tract syndromes (23 of 125 (19%)), urinary tract infection (24 of 125 (19%)) and wound infection (12 of 125 (10%)) were the most common syndromes identified. Bacteremic infections occurred in 35 of 125 (28%), and in 17 of 125 (14%) no other primary source could be identified. Pneumococci (11 of 35 (31%)) and Salmonella (4 of 35 (11%)) were the most common blood isolates; however, a wide spectrum of Gram-positive and Gram-negative pathogens were recovered. Bacterial pneumonia directly contributed to the death of 4 patients, in whom pneumonia caused by Pneumocystis carinii (2), cytomegalovirus (1) or varicella-zoster virus (1) also coexisted, respectively. Absolute T4 counts less than 400 and depressed lymphocyte-proliferative responses to diphtheria and tetanus toxoids, Candida antigen and pokeweed mitogen correlated with the occurrence of bacterial infection in human immunodeficiency virus-infected children. Although bacterial infections are a frequent cause of morbidity in human immunodeficiency virus-infected children, they are usually treatable.     

Evaluation and treatment of the human immunodeficiency virus-1--exposed infant

In developed countries, care and treatment are available for pregnant women and infants that can decrease the rate of perinatal human immunodeficiency virus type 1 (HIV-1) infection to 2% or less. The pediatrician has a key role in prevention of mother-to-child transmission of HIV-1 by identifying HIV-exposed infants whose mothers' HIV infection was not diagnosed before delivery, prescribing antiretroviral prophylaxis for these infants to decrease the risk of acquiring HIV-1 infection, and promoting avoidance of HIV-1 transmission through human milk. In addition, the pediatrician can provide care for HIV-exposed infants by monitoring them for early determination of HIV-1 infection status and for possible short- and long-term toxicities of antiretroviral exposure, providing chemoprophylaxis for Pneumocystis pneumonia, and supporting families living with HIV-1 infection by providing counseling to parents or caregivers.     

Combined therapy in human immunodeficiency virus-infected children —a 4-year experience

From 1988 to 1991 the long-term efficacy of a combined therapy with a polyvalent immunoglobulin/cytomegalovirus (CMV) hyperimmunoglobulin, oral low dose zidovudine, oral cotrimoxazole or inhaled pentamidine was investigated in three groups of human immunodeficiency virus (HIV)-infected children. Group 1A consisted of three perinatally infected children with a CD4 cell decrease of >400, cells/l per year. Group 1B were 17 perinatally infected children with a CD4 cell decrease of <400 cells/l per year. Group 2 comprised eight haemophilic children infected by clotting factors. Despite combined therapy none of group 1A survived longer than 12 months showing a rapid loss of CD4 cell counts, progressive encephalopathy, wasting syndrome and severe bacterial, fungal and CMV reactivation. Under pure intravenous immunoglobulin (IVIG) therapy severe bacterial infections were seen in 1 of 12 children in group 1B. The majority of these patients showed increases or stabilisation of length and weight percentiles. In this group low dose zidovudine therapy was of benefit in HIV-associated neurological symptoms. Nevertheless combined therapy could not prevent further deterioration of CD4 cell counts. In group 2 severe bacterial infections were not seen under IVIG therapy. In this group a temporary increase (6 months) of CD4 cell counts under IVIG/zidovudine combined therapy occurred.Pneumocystis carinii pneumonia (PCP) prophylaxis with oral cotrimoxazole or inhaled pentamidine successfully prevented PCP in all three groups. Under CMV hyperimmunoglobulins (n=22), ten out of ten patients did not acquire primary CMV infection, whereas CMV reactivations mainly located in the CNS could not be prevented in 5 of 12 patients. Our findings indicate that this combined therapy showed remarkable differences in therapeutic efficacy in children with different modes of HIV progression. These modes must be considered for correct timing, dosage and evaluation of therapeutic measures.     

Delayed recognition of human immunodeficiency virus infection in preadolescent children.

Thirty-two (18%) of 181 children cared for at our institution who were infected with the human immunodeficiency virus type 1 (HIV-1) were first seen, and HIV was diagnosed, when they were 4 years of age and older. Initial complaints or diagnoses for these children included the following: hematologic disorders (5) (3 idiopathic thrombocytopenic purpura, 1 neutropenia, 1 anemia); recurrent bacterial infections (10); Pneumocystis carinii pneumonia (3); developmental delay (1); skin disorders (2) (1 genital wart, 1 chronic zoster); weight loss (3); malignancy (1); and nephropathy (1). Eight children were referred for evaluation because of maternal HIV-1 infection. The risk factors for HIV-1 infection included maternal/perinatal exposure (22), perinatal blood transfusion (6), blood transfusion during infancy (2), and sexual abuse (2). Ten (31%) of the 32 children have subsequently died. The longest survival from perinatal infection was 12 years. HIV-1 infection in children can result in a prolonged clinical latency and can masquerade as other pathologic conditions. The absence of clinical symptoms in older children at risk for HIV-1 infection should not deter HIV testing.     

Enteroviral meningoencephalitis as a complication of X-linked hyper IgM syndrome

We describe 5 children from 2 families with mutations in the CD40 ligand (CD40L) gene leading to absent expression of CD40L on activated CD4 cells. All subjects presented with interstitial pneumonia with low serum IgG and normal serum IgM. One child had normal and one child had elevated serum IgA. Four had confirmed Pneumocystis carinii pneumonia. In spite of intravenous immunoglobulin treatment yielding therapeutic serum immunoglobulin levels, 3 children had enteroviral encephalitis. When assessed by flow cytometry, the 3 surviving affected male children had absent CD40L expression on activated CD4(+) T cells. The affected children from both families were shown to have the same single nucleotide insertion (codon 131) resulting in frameshift and early termination within exon 4 (extracellular domain). This observation demonstrates that persistent enteroviral infection is not only observed in X-linked agammaglobulinemia but may also occur in patients with X-linked hyper IgM syndrome.     

CD4 status and P24 antigenemia. Are they useful predictors of survival in HIV-infected children receiving antiretroviral therapy?

OBJECTIVE--To determine the relationship between CD4 status and the P24 antigen level and survival in children infected with the human immunodeficiency virus. DESIGN--Cohort, case-control. SETTING--Clinical Center at the National Institutes of Health, Bethesda, Md. PARTICIPANTS--One hundred forty-seven children infected with the human immunodeficiency virus enrolled in antiretroviral therapy protocols at the National Cancer Institute were reviewed and the relationships between CD4 counts, P24 antigenemia, and death were analyzed. INTERVENTIONS--None. MEASUREMENTS/MAIN RESULTS--The presence of a very low CD count, less than 21% of the lower limit of normal values for age (equivalent to 0.05 x 10(9)/L in an adult), was associated with a significantly increased risk of death within 2 years. Although the risk of death was highest for children with CD4 counts below this level and who had detectable P24 antigen levels, P24 antigenemia by itself contributed little to the prognostic value of the CD4 count alone. However, it was also notable that a group of children with low CD4 counts also experienced prolonged survival. CONCLUSIONS--The association between low CD4 counts and death suggests that the age-adjusted CD4 count should be used as a marker to guide therapeutic intervention. At the same time, the presence of a very low CD4 count alone should not be considered a reason for therapeutic nihilism.     

Pneumocystis carinii pneumonia in vertically acquired HIV infection in the British Isles

In order to review the clinical course, laboratory findings, and outcome of children with vertically acquired HIV infection and Pneumocystis carinii pneumonia, questionnaires were sent to paediatricians in the British Isles who had reported P carinii pneumonia and HIV infection through the British Paediatric Surveillance Unit (BPSU). Paediatric reports from the BPSU are linked to reports of pregnancies in HIV positive women and laboratory reports. P carinii pneumonia was the most frequently reported AIDS indicator disease at AIDS diagnosis, occurring in 22/56 (40%) children born in the British Isles; in a further two children P carinii pneumonia occurred after another AIDS indicator disease. The median age at P carinii pneumonia diagnosis was 4.1 (1.4-27.3) months and in 48% it occurred with other AIDS indicator diseases. Despite intensive treatment the three month survival was only 38%. The nine children surviving P carinii pneumonia subsequently developed further AIDS indicator diseases, in particular HIV encephalopathy and four have since died. P carinii pneumonia was present at AIDS diagnosis in 65% of children developing AIDS in the first year of life and caused 82% of infant deaths. Most children were not known to be at risk of HIV until they presented with P carinii pneumonia. Children with HIV infection develop P carinii pneumonia at an early age and have a poor outcome. Increased awareness of the condition is required to initiate early treatment. Prevention may be a compelling incentive for screening in pregnancy, but further study is required to quantify the risks and benefits of initiating early P carinii pneumonia prophylaxis as well as the impact this might have on life expectancy.     

Pneumocystis carinii pneumonia in vertically acquired HIV infection in the British Isles.

In order to review the clinical course, laboratory findings, and outcome of children with vertically acquired HIV infection and Pneumocystis carinii pneumonia, questionnaires were sent to paediatricians in the British Isles who had reported P carinii pneumonia and HIV infection through the British Paediatric Surveillance Unit (BPSU). Paediatric reports from the BPSU are linked to reports of pregnancies in HIV positive women and laboratory reports. P carinii pneumonia was the most frequently reported AIDS indicator disease at AIDS diagnosis, occurring in 22/56 (40%) children born in the British Isles; in a further two children P carinii pneumonia occurred after another AIDS indicator disease. The median age at P carinii pneumonia diagnosis was 4.1 (1.4-27.3) months and in 48% it occurred with other AIDS indicator diseases. Despite intensive treatment the three month survival was only 38%. The nine children surviving P carinii pneumonia subsequently developed further AIDS indicator diseases, in particular HIV encephalopathy and four have since died. P carinii pneumonia was present at AIDS diagnosis in 65% of children developing AIDS in the first year of life and caused 82% of infant deaths. Most children were not known to be at risk of HIV until they presented with P carinii pneumonia. Children with HIV infection develop P carinii pneumonia at an early age and have a poor outcome. Increased awareness of the condition is required to initiate early treatment. Prevention may be a compelling incentive for screening in pregnancy, but further study is required to quantify the risks and benefits of initiating early P carinii pneumonia prophylaxis as well as the impact this might have on life expectancy.     

Dysfunction of natural killer cells in human immunodeficiency virus-infected children with or without Pneumocystis carinii pneumonia.

The development of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected children with normal T-cell numbers is contrary to previous experience with HIV-infected adults, in whom low CD4+ T-cell numbers predict susceptibility to PCP. To determine whether PCP in HIV-infected children reflects a qualitative T-cell or other immune defect, we studied four HIV-infected children who also had PCP and 10 others without PCP for T-cell and natural killer (NK) cell function. Most of the HIV-infected children had normal T-cell numbers for age, and all had CD4+ T-cell numbers greater than those predictive of PCP in HIV-infected adults. All HIV-infected children had normal T-cell function in vitro. The HIV-infected children as a whole had deficient NK cell cytolysis. We obtained a significant interactive effect of age by health status for NK cell function between patients and age-matched control subjects. All HIV-infected children with defective NK cell function failed to enhance their NK cell cytolysis when their mononuclear cells were stimulated with recombinant interferon alfa (r-IFN-alpha). This NK cell defect in HIV-infected children may facilitate the development of secondary infection.     

Low-dose zidovudine in children with an human immunodeficiency virus type 1 infection acquired in the perinatal period

This report describes the one-year results of a noncomparative study designed to assess the safety and tolerance of low-dose zidovudine (azidothymidine) given orally to 60 human immunodeficiency virus type 1-infected infants and children. At baseline, the mean age was 1.9 years (+/- 1.4), and all were symptomatic: 43% were P2A and 57% were P2B to F according to the Centers for Disease Control classification. All the patients received zidovudine for at least 6 months, and 52 of them (87%) completed a full year of therapy. The mean duration of follow-up was 346 days (+/- 42) (range, 183 to 366 days). The initial therapy consisted of four daily doses of 100 mg/m2 (400 mg/m2 per day, equivalent to 20 mg/kg per day). However, this treatment was modified when neutropenia or anemia was observed. Twenty-nine children (48%) remained at the initial therapy for the entire study. Zidovudine dosage was adjusted 92 times in the other 31 children (52%), mostly due to neutropenia (83%). Altogether, the time under full-dose therapy represented 81% of the total duration of the protocol for all patients. Children with mild symptoms, P2A at study entry, were more likely to remain under full-dose therapy than children with severe symptoms, P2B to F: the time under full-dose therapy represented 91% of the duration of the protocol for the former group and only 74% for the latter one (P less than .02). No clinical adverse experiences were attributed directly to zidovudine. Thirty-seven children were prescribed trimethoprim-sulfametoxazole as a prophylaxis for Pneumocystis carinii pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Safety and tolerance of intermittent intravenous and oral zidovudine therapy in human immunodeficiency virus-infected pediatric patients. Pediatric Zidovudine Phase I Study Group

Thirty-five children with symptomatic human immunodeficiency virus infection were enrolled in a 12-week, three-center phase I study of intravenous and oral zidovudine therapy. At enrollment the children ranged in age from 5 months to 13 years, with a median age of 3 1/2 years. Twenty-one children (60%) had acquired immunodeficiency syndrome and 14 (40%) had the related complex; 20 children had less than 0.5 10(9) CD4+ lymphocytes per liter (less than 500 cells/mm3) at entry. Zidovudine was administered in one of three escalating dose regimens. One or two months of intravenous treatment with zidovudine every 6 hours was followed by orally administered drug on the same schedule; zidovudine was infused at 80, 120, or 160 mg/m2/dose, and the oral dose was one and one-half times the intravenous dosage. Adverse events were similar to those observed in adults. Neutropenia (absolute neutrophil count less than 0.75 10(9)/L (750 cells/mm3] occurred in nine patients. The median neutrophil count fell from 2.50 10(9)/L at entry to 1.72 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven patients; the median hemoglobin level among nontransfused patients decreased from an entry value of 108 to 105 gm/L (10.8 to 10.5 gm/dl). Dosage adjustments were made in 15 patients, in 12 because of anemia or neutropenia. No patients required permanent discontinuation of zidovudine because of toxic effects. Positive effects included a faster-than-anticipated rate of weight gain, decreased hepatosplenomegaly, and lowering of the total IgG and IgM concentrations toward more normal values. Zidovudine appears to be safe and to have manageable toxic effects in children.     

Trends in survival for children reported with maternally transmitted acquired immunodeficiency syndrome in New York City, 1982 to 1989.

To better understand the natural history of severe pediatric human immunodeficiency virus infection, reported cases of perinatally acquired pediatric acquired immunodeficiency syndrome (AIDS) in New York City were examined for differences in survival and age at diagnosis before and after implementation of an expanded case definition in 1987. One hundred ninety-six children reported through August, 1987, and 333 children reported between September, 1987, and February, 1990, and diagnosed through 1989 were compared. Significant differences were not found in survival by either gender or race/ethnicity although Hispanics were slightly more likely to be diagnosed with Pneumocystis carinii pneumonia (PCP) and blacks with lymphocytic interstitial pneumonitis (LIP). The most striking differences were noted regardless of race between children whose earliest AIDS-specific diagnosis was PCP and those whose earliest diagnosis was LIP. In the group reported through August, 1987, median survival from birth was 10 months with PCP vs. 54 months with LIP, median age at diagnosis 5 months vs. 20 months, and median survival after diagnosis 2 months vs. 22 months, respectively. Twelve-month survival for PCP improved in the two time periods examined, but survival with LIP did not. After implementation of the 1987 case definition, bacterial infections replaced LIP as the second most common diagnosis. This study provides data on children diagnosed and reported with AIDS. Ongoing prospective studies of children who have a full spectrum of human immunodeficiency virus infection with and without reportable AIDS wil further elucidate survival in children infected with human immunodeficiency virus.     

Prognostic significance of immunologic changes in 675 infants perinatally exposed to human immunodeficiency virus. The Italian Register for Human Immunodeficiency Virus Infection in Children.

Neutrophil, lymphocyte, and T-cell subset numbers and immunoglobulin levels were evaluated at birth to age 2 years in 675 children born to mothers infected with the human immunodeficiency virus type 1 (58 infected symptom-free subjects (P-1), 203 infected subjects with symptoms (P-2), and 414 uninfected subjects). The P-2 patients had (even at birth to age 1 month) lower CD4+ lymphocyte and higher IgA and IgM values than P-1 and uninfected children had. Increased IgG values (from 1 to 6 months of age) and increased CD8+ lymphocyte numbers (at 13 to 24 months of age) were also observed. The P-1 children differed from uninfected children only at 13 to 24 months of age (decreased CD4+ and increased CD8+ lymphocytes). Progressive immunologic changes were found in P-2 patients who had severe clinical conditions and in those who died. To evaluate the predictive meaning of the immunologic changes, we selected 164 children (25 P-2, 15 P-1, and 124 uninfected children) because they had been examined sequentially from birth and they were classified as in the indeterminate state of infection (P-0) at immunologic evaluations at birth to age 1 and at 1 to 6 months of age. During the 1- to 6-month period, P-2 patients had higher immunoglobulin and lower CD4+ lymphocyte values than P-1 and uninfected children had; no difference was found between P-1 and uninfected subjects. These results indicate that in infants with perinatal human immunodeficiency virus type 1 infection, immunologic abnormalities correlate with the clinical condition and are predictive of the clinical outcome rather than the infection status.     

Pneumocystis carinii pneumonia in patients with Diamond-Blackfan anemia receiving high-dose corticosteroids

The authors describe three infants with Diamond-Blackfan anemia receiving corticosteroids who were diagnosed with Pneumocystis carinii pneumonia. Two patients exhibited intermittent neutropenia as well. Each child had been receiving relatively high doses of corticosteroids for at least 2 months, and two were having prednisone tapered when pneumonia developed. One child responded to trimethoprim/sulfamethoxazole and pentamidine, but the other two patients died. Infants with Diamond-Blackfan anemia receiving prolonged corticosteroid therapy should receive P. carinii pneumonia prophylaxis, such as trimethoprim/sulfamethoxazole, and prophylaxis should continue during corticosteroid tapering.     

Epidemiology of pediatric Human Immunodeficiency Virus infection in the United States

Human Immunodeficiency Virus (HIV) infection is a growing problem for children worldwide. As of 31 December 1992, 4249 children with Acquired Immunodeficiency Syndrome (AIDS) under 13 years of age had been reported to the US Centers for Disease Control and Prevention (CDC). HIV is transmitted to children predominantly from their mothers. Nearly all cases of HIV infection acquired from blood transfusions in the United States occurred before donor-screening practices were implemented in March 1985. In 1991, approximately 7000 HIV-infected women gave birth to a liveborn infant in the United States, for a prevalence of 1.7 per 1000 women. Despite recent advances in prophylactic therapy for opportunistic infections, Pneumocystis carinii pneumonia remains the most common AIDS-defming illness in children in the United States. If these cases are to be prevented, children born to HIV-infected mothers will need to be identified early and monitored appropriately for CD4+ cell counts to determine the need for prophylaxis.     

An outbreak of Pneumocystis carinii pneumonia at a pediatric hospital.

Eleven cases of Pneumocystis carinii pneumonia were diagnosed during a 3 1/2-year period at a pediatric hospital where this infection had never been identified previously despite appropriate studies. The incidence of infection was 3.0, 7.4, and 4.2 cases per 1,000 patient months in children being treated for acute leukemia, neuroblastoma, and rhabdomyosarcoma, respectively. The outbreak coincided with increased intensity of chemotherapy for these malignancies. Ten of the patients had received four or more chemotherapeutic agents within three months of the onset of infection. Because no exogenous source of the epidemic was found, latent endogenous infection activated by immunosuppression was presumed to be the ultimate cause of the outbreak. Increased intensity of chemotherapy may result in P carinii outbreaks and may be an indication for anti-Pneumocystis prophylaxis with trimethoprim/sulfamethoxazole in patients at risk.     

Respiratory manifestations in HIV-infected children pre- and post-HAART in Abidjan, the Ivory Coast

Among children infected with human immunodeficiency virus (HIV), respiratory diseases are a frequent cause of morbidity and mortality. This review describes respiratory manifestations of paediatric HIV infection before and after the beginning of HAART in Abidjan, Ivory Coast. In an observational cohort, HIV infected children had quarterly clinical visits and a day-clinic available all week for ill children. CD4 and viral load were measured at baseline and every 6 months thereafter. All children with a CD4 percentage below 25% were prescribed daily cotrimoxazole prophylaxis. Ninety-eight children (of a total of 282) were recruited before HAART and treated during the follow-up, there were 56 boys and 42 girls, with a mean age of 6.2 years at inclusion. The mean percentage of CD4 before HAART was 8.7%. Twelve children had a history of pulmonary tuberculosis and five were on antituberculosis treatment at inclusion. Fifty-one per cent presented with abnormalities on chest X-ray at inclusion. Before initiation of HAART, respiratory manifestations represented 32.4% of morbidity events and the incidence for 100 child/months was 9.29 for URTI, 15.2 for bronchitis, 6.07 for LRTI, 0.71 for tuberculosis and 0.36 for Pneumocystis carinii. After the initiation of HAART, respiratory manifestations represented 40.9% of all morbidity events and the incidence for 100 child/months was 5.35 for URTI, 9.48 for bronchitis, 2.17 for LRTI and 0.16 for tuberculosis. During HAART treatment, the incidence of respiratory infections decreased dramatically compared to before the antiretroviral treatment. However, respiratory events still represented 40% of all events occurring following the start of HAART therapy.