Metabolic abnormalities and viral replication are associated with biomarkers of vascular dysfunction in HIV-infected children.

OBJECTIVES: HIV-infected children may be at risk for premature cardiovascular disease. We compared levels of biomarkers of vascular dysfunction in HIV-infected children (with and without hyperlipidaemia) with those in HIV-exposed, uninfected (HEU) children enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS), and determined factors associated with these biomarkers. METHODS: A prospective cohort study was carried out. Biomarkers of inflammation [C-reactive protein (CRP), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP1)], coagulant dysfunction (fibrinogen and P-selectin), endothelial dysfunction [soluble intracellular cell adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM) and E-selectin], and metabolic dysfunction (adiponectin) were measured in 226 HIV-infected and 140 HEU children. Anthropometry, body composition, lipids, glucose, insulin, HIV disease severity, and antiretroviral therapy were recorded. RESULTS: The median ages of the children were 12.3 years in the HIV-infected group and 10.1 years in the HEU group. Body mass index (BMI) z-scores, waist and hip circumferences, and percentage body fat were lower in the HIV-infected children. Total and non-high-density lipoprotein (HDL) cholesterol and triglycerides were higher in HIV-infected children. HIV-infected children also had higher MCP-1, fibrinogen, sICAM and sVCAM levels. In multivariable analyses in the HIV-infected children alone, BMI z-score was associated with higher CRP and fibrinogen, but lower MCP-1 and sVCAM. Unfavourable lipid profiles were positively associated with IL-6, MCP-1, fibrinogen, and P- and E-selectin, whereas increased HIV viral load was associated with markers of inflammation (MCP-1 and CRP) and endothelial dysfunction (sICAM and sVCAM). CONCLUSIONS: HIV-infected children have higher levels of biomarkers of vascular dysfunction than do HEU children. Risk factors associated with higher biomarkers include unfavourable lipid levels and active HIV replication.

Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy.

The role of the thymus in HIV-1 pathogenesis remains unclear. We developed an assay to quantify the number of recent thymic emigrants in blood based on the detection of a major excisional DNA byproduct (termed alpha1 circle) of T cell receptor rearrangement. By studying 532 normal individuals, we found that alpha1 circle numbers in blood remain high for the first 10-15 yr of life, a sharp drop is seen in the late teen years, and a gradual decline occurs thereafter. Compared with age-matched uninfected control individuals, alpha1 circle numbers in HIV-1-infected adults were significantly reduced; however, there were many individuals with normal alpha1 circle numbers. In 74 individuals receiving highly active antiretroviral therapy, we found no appreciable effect on alpha1 circle numbers in those whose baseline values were already within the normal range, but significant increases were observed in those with a preexisting impairment. The increases in alpha1 circle numbers were, however, numerically insufficient to account for the rise in levels of naive T lymphocytes. Overall, it is difficult to invoke thymic regenerative failure as a generalized mechanism for CD4 lymphocyte depletion in HIV-1 infection, as alpha1 circle numbers are normal in a substantial subset of HIV-1-infected individuals.

Erythrocyte adenosine deaminase deficiency without immunodeficiency. Evidence for an unstable mutant enzyme.

Inherited deficiency of the purine salvage enzyme adenosine deaminase (ADA) gives rise to a syndrome of severe combined immunodeficiency (SCID). We have studied a 2.5-yr-old immunologically normal child who had been found to lack ADA in his erythrocytes during New York State screening of normal newborns. His erythrocytes were not detectably less deficient in ADA than erythrocytes of ADA(-)-SCID patients. In contrast, his lymphocytes and cultured long-term lymphoid cells contained appreciably greater ADA activity than those from patients with ADA(-)-SCID. This residual ADA activity had a normal molecular weight and K(m) but was markedly unstable at 56 degrees C. His residual erythrocytes-ADA activity also appeared to have diminished stability in vivo. ADA activity in lymphoid line cells of a previously reported erythrocyte-ADA-deficient!Kung tribesman was found to contain 50% of normal activity and to exhibit diminished stability at 56 degrees C. ATP content of erythrocytes from both partially ADA-deficient individuals was detectably greater than normal (12.3 and 6.1 vs. normal of 2.6 nmol/ml packed erythrocytes). However, the dATP content was insignificant compared to that found in erythrocytes of ADA(-)-SCID patients (400-1,000 nmol/ml packed erythrocytes). The New York patient, in contrast to normals, excreted detectable amounts of deoxyadenosine, but this was <2% of deoxyadenosine excreted by ADA(-)-SCID patients. Thus, the residual enzyme in cells other than erythrocytes appears to be sufficient to almost totally prevent accumulation of toxic metabolites.

The EPIICAL project: an emerging global collaboration to investigate immunotherapeutic strategies in HIV-infected children.

The EPIICAL (Early-treated Perinatally HIV-infected Individuals: Improving Children's Actual Life with Novel Immunotherapeutic Strategies) project arises from the firm belief that perinatally infected children treated with suppressive antiretroviral therapy (ART) from early infancy represent the optimal population model in which to study novel immunotherapeutic strategies aimed at achieving ART-free remission. This is because HIV-infected infants treated within 2-3 months of life have a much reduced viral reservoir size, and rarely show HIV-specific immunity but preserve normal immune development. The goal of EPIICAL is the establishment of an international collaboration to develop a predictive platform using this model to select promising HIV therapeutic vaccine candidates, leading to prioritisation or deprioritisation of novel immunotherapeutic strategies. To establish this platform, the EPIICAL Consortium aims to: develop predictive models of virological and immunological dynamics associated with response to early ART and to treatment interruption using available data from existing cohorts/studies of early-treated perinatally HIV-infected children; optimise methodologies to better characterise immunological, virological and genomic correlates/profiles associated with viral control; test novel immunotherapeutic strategies using in vivo proof-of-concept (PoC) studies with the aim of inducing virological, immunological and transcriptomic correlates/profiles equivalent to those defined by the predictive model. This approach will strengthen the capacity for discovery, development and initial testing of new therapeutic vaccine strategies through the integrated efforts of leading international scientific groups, with the aim of improving the health of HIV-infected individuals.

The sensitivity of HIV-1 DNA polymerase chain reaction in the neonatal period and the relative contributions of intra-uterine and intra-partum transmission.

OBJECTIVE: To derive reliable estimates of the sensitivity of HIV-1 DNA polymerase chain reaction (PCR) in the neonatal period and to quantify the relative contributions of intra-uterine and intra-partum transmission. METHODS: After reviewing studies on the early diagnosis of HIV-1 infection, investigators were asked to provide published and unpublished PCR test results on prospectively followed, non-breastfed, vertically infected children. Age-specific estimates of the sensitivity of PCR were derived using distribution-free methods for interval-censored data. RESULTS: Data on 271 infected children were combined for analysis. PCR detected HIV-1 DNA in an estimated 38% [90% confidence interval (CI), 29-46] of HIV-infected children tested on the day of, or day after, birth. Sensitivity was observed to rise rapidly in the second week of life, reaching 93% (90% CI, 76-97) by 14 days of age. CONCLUSION: The sensitivity of PCR in the neonatal period is higher than previously reported. This affects the clinical interpretation of an early negative test result and encourages the use of PCR as an endpoint for trials to evaluate interventions to reduce vertical transmission in non-breastfed populations. Approximately one-third of vertically acquired HIV-1 infection could be attributable to intra-uterine transmission.

CD8+ T-cell-mediated suppression of HIV replication in the first year of life: association with lower viral load and favorable early survival.

OBJECTIVE AND DESIGN: To study the role and development of non-cytotoxic CD8+ T-cell-mediated suppression of HIV replication in early perinatal HIV infection in a prospective study of vertically infected infants. CD8 T-cell-mediated HIV suppression was measured several times during the first year of life and correlated with viral load, cytotoxic T-cell (CTL) activity, in vitro antibody production (IVAP) and clinical outcome. METHODS: CD8+ T-cell-mediated HIV suppression was measured by comparing the amount of p24 antigen produced by endogenously infected lymphocytes with cultures of the same number of autologous CD4+ T cells from which CD8+ cells were removed immunomagnetically. CD8 viral suppressive activity (VSA) was defined as a > or = 50% reduction in p24 antigen in the cultures containing CD8+ cells. RESULTS: CD8+ T-cell-mediated HIV VSA was detected in 11/16 infants in the first year of life, including six/nine infants studied before 6 months and as early as 3 weeks of age. Infants who demonstrated CD8 VSA had a lower early peak and 6-month 'setpoint' plasma HIV RNA concentration than infants who lacked CD8 VSA [1.51 versus 4.94 and 0.094 versus 0.639 x 10(6) copies/ml, respectively, and higher CD4 percentage at 1 year of age. Survival of infants lacking CD8 VSA (four/six were rapid progressors) was shorter than for infants who demonstrated CD8 VSA (none out of 10 were rapid progressors). CD8 VSA was present before CTL and before or at the same time as IVAP in two of two and 11 of 14 infants studied, respectively. CONCLUSIONS: CD8+ T-cell-mediated VSA can be demonstrated in a large proportion of HIV-infected infants early in the course of infection. This non-cytolytic HIV-suppressive immune response appears to play an important protective role in the early control of perinatal HIV infection at a time when other immune responses are either absent or deficient.

Immunologic and virologic responses to HAART in severely immunocompromised HIV-1-infected children.

OBJECTIVE: To determine the long-term immunologic and virologic effects of highly active antiretroviral therapy (HAART) in children with AIDS. DESIGN: A prospective observational study. SETTING: Two pediatric HIV clinics. PARTICIPANTS: Twenty-five protease-inhibitor naive HIV-infected children (aged 2-18 years) with advanced disease (CD4 < or =6%). INTERVENTION: HAART (one protease inhibitor and one or more nucleoside analogs). Diphtheria and tetanus immunization in six patients after 18 months of therapy. MAIN OUTCOME MEASURES: Changes in percentage of CD4 cells and plasma HIV-1 RNA levels; post-treatment assays of lymphoproliferative responses to recall antigens; CD4 cell memory phenotype. RESULTS: Median duration of follow-up was 18.8 months (range, 7.5-28 months). At baseline the CD4 cell percentage was 2% (range, 0-6%), this increased significantly to 16% (range, 3-48%) above baseline at 12 months (P = 0.002). The mean maximum CD4 cell increase was 20.7% (range 4-48%) which corresponds to 657x10(6) cells/l (range, 30-2240x10(6) cells/l) above baseline. By contrast, the median viral load was not significantly lower at 12 months than at baseline (P = 0.34), and only 25% of the patients had sustained undetectable viral load. Of the reconstituted CD4 cells 70% were naive, and none of the subjects had lymphoproliferative responses to tetanus and diphtheria although 40% did develop responses to Candida, an environmental antigen. A single immunization with diphtheria and tetanus toxoid produced lymphoproliferative responses to tetanus in three out of six patients. CONCLUSIONS: HAART was associated with sustained increases in CD4 cell counts, despite a high incidence of 'virologic failure'. CD4 counts and the proportion of naive cells were higher than have been reported in adults, which may be a reflection of greater thymic activity in children. Memory cell clones for antigens encountered in the past which are not prevalent before therapy could not be expanded without additional antigenic exposure.

Protective effect of interferon-alpha against cell-mediated human immunodeficiency virus transmission resulting from coculture of infected lymphocytes with fetal trophoblasts.

The hypothesis that the low transmission rate of HIV in utero may be due, in part, to the protective effect of IFN-producing placental trophoblasts was explored in vitro. The model consisted of H9 lymphocytes, as surrogates of maternal HIV-infected T cells, incubated for 3 h with JEG-3 trophoblasts in the presence of 10-fold dilutions of leukocyte-derived IFN-alpha (from 1000 to 0.1 IU/ml). The dose effect was monitored either directly, by measuring the levels of proviral DNA by PCR after a single round of infection, or indirectly, by coculturing infected JEG-3 with cord blood-derived MT-4 lymphocytes and determining the levels of p24 production by ELISA. Both assays revealed a dose-dependent blocking effect of IFN-alpha on cell-mediated HIV transmission. The complete inhibition of HIV infection was observed in the presence of 100 IU IFN-alpha. The efficacy of such a low dose could not be attributed to insufficient viral load because up to 10(8) infectious particles could be transmitted during cell-cell contact. An adhesion assay ruled out the possibility that IFN-alpha acts through prevention of lymphocyte-trophoblast contact. The results suggest that physiologic levels of IFN-alpha, present in the placental environment, may contribute to the protection of the fetus against HIV infection.

A novel detection assay for the early diagnosis of HIV-1 infected infants.

This investigation compares the results of a new method of diagnosing HIV-1 infection in infants < 6 months of age with currently employed techniques including cocultivation, the polymerase chain reaction (PCR), serum p24 antigen, and in vitro antibody production (IVAP) measurements. The new method, called in vitro antigen (IVAG), measures p24 antigen released into culture supernatants of peripheral blood mononuclear cells that are incubated with Epstein-Barr virus (EBV). No activated donor lymphocytes or interleukin 2 (IL-2) are added to the culture. Using this technique, HIV-1 infection was detected in 15 of 17 HIV-1-infected infants < 2 months of age, including 3 of 7 infants tested at birth, and 15 of 15 HIV-1-infected infants between 2 and 6 months of age. None of 83 determinations of 15 uninfected infants were positive. These results were found to be comparable to results obtained by the traditional cocultivation technique and the polymerase chain reaction. Because of its simplicity and reduced cost, this sensitive and specific assay could be a valuable addition to the current methods of diagnosis of HIV-1 infection in young infants.

Perinatal human immunodeficiency virus infection: ruminations on mechanisms of transmission and methods of intervention.

Perinatal human immunodeficiency virus (HIV) infection is undoubtedly a multifactorial process. Neither the quantity of viremia nor the level of neutralizing antibody in the infected mother is alone predictive of HIV transmission to her offspring. Additional cofactors may include the ability of maternal immunity to control the host cell range and rate of viral replication. The placenta probably constitutes an effective barrier to viral transmission unless disrupted by processes such as syphilis. Prevention of such breaks in the trophoblast barrier and efforts to stimulate maternal and newborn HIV-specific immunity may further decrease the perinatal transmission rate.

Alteration in the proportion of CD4 T lymphocytes in a subgroup of human immunodeficiency virus-exposed-uninfected children.

OBJECTIVE: The age-related changes in the proportion of CD4 and CD8 lymphocytes in human immunodeficiency virus (HIV)-seronegative children born to HIV-infected mothers (seroreverters) were compared with the changes in these lymphocyte subsets in children born to seronegative women to assess a possible effect of exposure to HIV without infection. DESIGN: There were 146 seroreverter and 72 seronegative children. The median CD4 and CD8 percentages for each of these two groups of children were compared retrospectively at 3-month intervals from birth through 27 months and at a tenth interval for the time beyond 27 months. The weighted average of the within-subject rate of change of CD4 and CD8 percentages were also compared between the two groups. Finally, for each subject, the proportion of the subject's CD4 percentage assays which were <10th percentile of the entire study population (30%) was calculated, and the distributions of the subject-specific proportions were then compared between the seronegative and seroreverter groups using the Wilcoxon rank sum test. The proportion of CD8 assays <10th percentile (12%) or > 90th percentile (26%) were also computed for each subject, and the distributions of the proportions were compared similarly. . RESULTS: The median CD4 percentage of seroreverter children was lower than that for the seronegative children at every interval from birth through 27 months and for the last interval for values obtained at greater than 27 months, although the comparison was statistically significant only at the 4- to 6-month period. The weighted average of the within-subject rate of change of CD4 percentage was -0.09 and -3.0 per year (P = .04), and of CD8 percentage was 1.3 and 1.0 (P = .67), for the seroreverter and seronegative children, respectively. There were significantly more children in the seroreverter group than in the seronegative group who had repeated assays in which the CD4 percentage was < 10th percentile for age (P < .00005). In addition, there was a subset of 10 seroreverter children (6.8%) who had CD4 percentages < 30% on > 50% of their assays, as compared with only one (1.4%) seronegative child. The proportion of CD8 assays < 10th percentile or > 90th percentile were not significantly different between the two groups of children. CONCLUSIONS: The CD4 proportions were persistently lower in the seroreverter than in the seronegative population, although only reaching statistical significance in 1 of 10 3-month intervals. This finding may be due to a subgroup of seroreverter children who have persistently low CD4 lymphocyte percentages.

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.

Lymphocyte proliferative responses to HIV-1 envelope and core antigens by infected and uninfected adults and children.

Lymphocytes derived from children and adults infected with the human immunodeficiency virus (HIV-1), as well as from seronegative children and adults, were tested for their ability to proliferate in response to recombinant HIV envelope (env) and core (cor) peptides. Proliferative responses to env were seen in 9% of control children compared with 27% of infected children (p less than 0.02). There was no difference in the response rates of seropositive and seronegative adults (17% and 16%, respectively). Proliferative responses to cor were seen more frequently in children and adults (22% and 28%, respectively) than their seronegative cohorts (11% and 12%, respectively). Also, the proliferative response to env and cor was seen in 27% and 37%, respectively, of seronegative children who were born to seropositive mothers and then subsequently seroreverted. These results suggest that sensitization to HIV recombinant antigens has resulted in a cell-mediated immune response in some HIV-infected individuals. Furthermore, the significant cell-mediated immune response to these antigens in seroreverting children raises the possibility that they may have been sensitized to this antigen by previous HIV infection.

Early changes in quasispecies repertoire in HIV-infected infants: correlation with disease progression.

The evolution of HIV-1 quasispecies in patients during the first year of life was investigated in 10 vertically infected infants, using heteroduplex analysis of the V3-V5 region of env. Four subjects, who showed little viral evolution during the period of the study, had rapid progression of disease and early loss of CD4(+) cells. The remaining six subjects, who were slow progressors, evolved new viral variants within 6 months, and in one case by 1 month of age. Of the four patients who were PCR positive at birth, one was infected with multiple HIV-1 variants. These results show that in HIV-infected children, multiple variants may initiate infection and early quasispecies diversification is associated with a favorable clinical outcome.

Production of a human anti-CD4 monoclonal antibody with antiidiotype to anti-HIV type 1 glycoprotein 120.

Human anti-CD4 IgG antibodies from 3 HIV-1-infected patients were affinity purified and shown to inhibit HIV-1 binding and infection of HBP-T cells. Lymphocytes from patient A, whose anti-CD4 inhibited HIV-1 binding by 68% and infection by 72%, were cultured and transformed with EBV. A human monoclonal antiidiotype antibody against anti-HIV-1 gp120 (2B) was produced, which inhibited infection of HBP-T cells by 68% at 1 microgram/ml. Mice were immunized with 2B to determine whether this anti-CD4 could be an internal image antiidiotype against anti-HIV-1 gp 120 (Ab1). Two mice produced antisera reactive with rgp120 on ELISA, whereas immunization with normal IgG produced minimal reactivity compared to unreactive normal mouse sera. However, immunoblot competition studies in which affinity-purified anti-HIV-1 gp120 (Ab1) bound to the gp120 band on nitrocellulose strips in the presence of 2B demonstrated enhancement of signal (i.e., binding of Ab2 to Ab1), rather than inhibition of Ab1 binding. Thus 2B is not an internal image of the paratope of anti-HIV-1 gp120 but yet it is capable of inducing an antibody against rgp120. This indicates that the anti-CD4 (Ab2) does bind to the binding site of Ab1, but not as a complete internal image. These data indicate the production of a human monoclonal antiidiotype antibody that inhibits binding of HIV-1 to CD4 and induces the production of antibody against HIV-1 gp120, without being an internal image antiidiotype (Ab2 beta).

Antibodies to human immunodeficiency virus type 1 in the urine specimens of HIV-1-seropositive individuals.

Specific antibodies to human immunodeficiency virus type 1 (HIV-1) were detected in 200-fold concentrated urine samples, but none were detected in unconcentrated urine specimens, from 100 randomly selected HIV-1--seropositive individuals by enzyme-linked immunosorbent assay (ELISA) and Western blot techniques using the manufacturer's recommended procedures. Using modified methods for both the ELISA and Western blot tests, antibodies to HIV-1 have also been detected in the unconcentrated urine specimens from the same HIV-1--seropositive individuals. No difference in the frequency of antibodies to HIV-1 were found between unconcentrated and 200-fold concentrated urine samples when tested by the modified methods. HIV-1 core antigen (p24) was not detected in either the concentrated or the unconcentrated HIV-1--seropositive adult urine samples; none of these individuals showed overt clinical or laboratory evidence of renal dysfunction. The titer of the antibodies to HIV-1 found in the urine specimens was found to be parallel with the titer of antibodies to HIV-1 in the corresponding individual's serum. Further elucidation of the pathophysiology and the nature of the specific antibodies to HIV-1 observed in the urine of HIV-1--seropositive individuals is under investigation in our laboratories.

Expression patterns of the HIV type 1 coreceptors CCR5 and CXCR4 on CD4+ T cells and monocytes from cord and adult blood.

We have measured the surface expression of the HIV-1 coreceptors CCR5 and CXCR4 on CD4+ T cells and monocytes from cord and adult blood. The expression of CCR5 was largely restricted to the memory (CD45RAlow) subset, whereas CXCR4 was expressed on both memory and naive (CD45RAhigh) T cells. The paucity of memory CD4+ T cells in cord blood means that CCR5-positive cells are relatively uncommon, so the overall extent of CCR5 expression was reduced in cord blood, compared with adult blood. IL-2 activation of CD4+ T cells from both cord and adult bloods caused a substantial increase in CCR5 expression, but moderately decreased CXCR4 expression. PHA stimulation increased CCR5 expression slightly, but only on naive cells. Monocytes expressed both CCR5 and CXCR4 at levels that differed little between cord and adult blood.

Prognosis of human immunodeficiency virus infection in children and adolescents.

The prognosis of 111 children and adolescents (from 2.5 months to 19.5 years of age) infected with human immunodeficiency virus (HIV) was assessed by survival analysis based on risk factors and clinical status. Risk factors included: maternal HIV infection 93; transfusion 12; both maternal HIV infection and transfusion 2; sexual abuse 1; and intravenous drug use and/or sexual activity 3. Children with perinatal infection survived from 2.5 months to 10.25 years (median, 1.87 years) and had inapparent infection from 6 weeks to 7.3 years (median, 0.75 years). Children who acquired HIV infection via transfusion had inapparent infection from 4 months to 5.7 years (median, 3.6 years). Actuarial survival following infection was not significantly different from maternally and transfusion-acquired infection; however, survival from infection was longer for children infected by transfusion beyond 2 years of age (mean, 7.5 years) than for children infected perinatally (mean, 5.6 years). The case-fatality ratio was 32%, with 25% of subjects succumbing within 1 year of developing an HIV-associated illness. Opportunistic infection was the most common acquired immunodeficiency syndrome-defining illness and the cause of death in 22 of the 35 children who died. Pneumocystis carinii and fungal pneumonias had the worst prognosis. Cryptosporidiosis and other opportunistic infections had a better prognosis. Because of difficulties in case finding, diagnosis of infection and variable survival of HIV-infected children, arge longitudinal studies and pooling of data among centers will be necessary to have an accurate understanding of the prognosis of individual clinical syndromes.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Lack of predictive value of maternal human immunodeficiency virus p24 antigen for transmission of infection to their children.

The association of maternal-to-infant transmission of human immunodeficiency virus type 1 (HIV-1) with maternal p24 antigenemia was assessed in 86 HIV-1-infected mothers. We retrospectively examined serum or plasma samples collected in the peripartum period (delivery +/- 11 days; sd 16.89 days; range, delivery +/- 2 months). Immune complexes of p24 antigen and anti-p24 antibody were dissociated using acid hydrolysis (Method A, glycine-HCl buffer; Method B, HCl) in an attempt to increase the sensitivity of the test. The detection of HIV-1 p24 antigenemia in serum was increased from 23 of 86 (26.7%) to 37 of 82 (45.1%) following acid hydrolysis with Method A (chi square = 5.4, P = 0.02) and to 36 of 78 (46.1%) with Method B (chi square = 5.874, P = 0.015). Mothers of HIV-1-infected children were no more likely to have p24 antigenemia than mothers of seroreverted infants when untreated samples were assayed (7 of 23 vs. 10 of 48; chi square = 0.348, P = 0.55). Although acid hydrolysis increased the ability to detect p24 antigen, it did not enhance any association between p24 antigenemia and maternal-to-infant transmission of HIV infection: Method A, 9 of 23 in mothers of infected children vs. 21 of 45 in mothers of seroreverted children (chi square = 0.112, P = 0.738); and Method B, 9 of 22 in mothers of infected children vs. 18 of 42 in mothers of seroreverted children (chi square = 0.014; P = 0.907), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)