Predictors of growth and body composition in HIV-infected children beginning or changing antiretroviral therapy.

OBJECTIVES: The aim of the study was to describe growth and body composition changes in HIV-positive children after they had initiated or changed antiretroviral therapy (ART) and to correlate these with viral, immune and treatment parameters. METHODS: Ninety-seven prepubertal HIV-positive children were observed over 48 weeks upon beginning or changing ART. Anthropometry and bioelectrical impedance analysis results were compared with results from the National Health and Nutrition Examination Survey 1999-2002 (NHANES) to generate z-scores and with results for HIV-exposed, uninfected children from the Women and Infants Transmission Study (WITS). Multivariate analysis was used to evaluate associations between growth and body composition and disease parameters. RESULTS: All baseline lean and fat mass measures were below those of controls from NHANES. Weight, height and fat free mass (FFM) index (FFM/height(2)) z-scores increased over time (P = 0.004, 0.037 and 0.027, respectively) and the waist:height ratio z-score decreased (P = 0.045), but body mass index and per cent body fat z-scores did not change. Measures did not increase more than in uninfected WITS controls. In multivariate analysis, baseline height, mid-thigh circumference and FFM z-scores related to CD4 percentage (P = 0.029, P = 0.008 and 0.020, respectively) and change in FFM and FFM index z-scores to CD4 percentage increase (P = 0.010 and 0.011, respectively). Compared with WITS controls, baseline differences in height and mid-thigh muscle circumference were also associated with CD4 percentage. Case-control differences in change in both subscapular skinfold (SSF) thickness and the SSF:triceps skinfold ratio were inversely associated with viral suppression. No measures related to ART class(es) at baseline or over time. CONCLUSIONS: In these HIV-positive children, beginning or changing ART was associated with improved growth and lean body mass (LBM), as indicated by FFM index. Height and LBM related to CD4 percentage at baseline and over time. Altered fat distribution and greater central adiposity were associated with detectable virus but not ART class(es) received.

Point-of-use water filtration reduces healthcare-associated infections in bone marrow transplant recipients.

Outbreaks of infection with gram-negative bacteria (GNB) have been linked to hospital water. We sought to determine whether point-of-use (POU) water filtration might result in decreased risk of infection in hospitalized bone marrow transplant (BMT) recipients in the absence of any recognized outbreak. Unfiltered water was sampled from taps in the BMT unit of a major US teaching hospital, and cultured at a reference laboratory. POU bacterial-retentive filters (0.2 mum) were installed throughout the unit, and replaced every 14 days. Infection rates were tracked over a 9-month period, and compared with rates for a 16-month period before POU filtration. Unfiltered water samples from 50% (2 of 4) outlets sampled grew P. aeruginosa (2 of 4) and Stenotrophomonas maltophilia (1 of 4). Clinical infection rates in the unit were significantly reduced from 1.4 total and 0.4 GNB infections per 100 patient days in the period before POU filtration to 0.18 total and 0.09 GNB infections per 100 patient days (P=0.0068 and 0.0431, respectively) in the 9-month period for which filters were in place. Infections during the POU filtration period were due to non-waterborne organisms. Point-of-use (POU) water filtration may significantly reduce infection rates in BMT recipients in the absence of any recognized outbreak.

Impact of protease inhibitor-containing combination antiretroviral therapies on height and weight growth in HIV-infected children.

OBJECTIVE: To examine beneficial or detrimental effects of protease inhibitor (PI)-containing antiretroviral regimens on height and weight growth in children with human immunodeficiency virus (HIV) infection. METHODS: A prospective cohort study was conducted of 906 HIV-infected children, from pediatric research clinics in the United States, who were between 3 months and 18 years of age and who had height and weight assessed in 1995 (before introduction of PIs in this population) and at least once more through 1999. Changes in age- and gender-adjusted height and weight growth associated with PI use were assessed. RESULTS: Compared with a healthy reference population, children were more affected in height (mean z score: -0.90 [18th percentile]) than in weight (mean z score: -0.42 [34th percentile]) at baseline (1995). Two thirds of children received at least 1 PI during 1996 to 1999. In the multivariate mixed effects regression models adjusted for baseline log(10) CD4 cell count, baseline age, gender, and race/ethnicity, the use of PIs was associated with per-year gains of 0.13 z scores in height and 0.05 z scores in weight relative to the expected growth with non-PI-containing regimens (eg, after 1 year of PI use, a representative 6-year-old boy in our study would be approximately 0.7 cm taller and 0.1 kg heavier than if he had not received PIs). No significant differential effects of PIs on height or weight growth according to specific agents or children's sociodemographic or clinical characteristics were found. CONCLUSIONS: Although the use of PI-containing regimens was not associated with growth retardation, it was associated with only small annual increments in height and weight growth in HIV-infected children.

Characteristics of human immunodeficiency virus-infected children at the time of death: an experience in the 1990s.

OBJECTIVE: To describe the changes in the characteristics of human immunodeficiency virus (HIV)-related deaths in children with perinatally acquired infection. METHODS: A retrospective review of all deaths that occurred in HIV-infected children managed at The New York Hospital-Program for Children with AIDS during a 7-year period from January, 1990, to December, 1996. Differences in the characteristics at death between 15 children who died in 1990 and 10 children who died in 1996 were analyzed. RESULTS: Fifty-eight deaths in our cohort of HIV-infected children were identified during the 7-year period. The mean age at death was 4.43 years. Sixty-nine percent of children were black, 55% were male and 94% were receiving Medicaid. The mean weight/age Z score was -3.9 and the mean CD4 index was 0.067 with 65% having <50 CD4 cells/microl at the time of death (TOD). The most common organ/organ systems to be involved at the TOD were lung (78%) and central nervous system (61%). Mycobacterium avium complex (MAC) was the most common isolate at the TOD (26%) followed by Pneumocystis carinii (20%) and Pseudomonas aeruginosa (17%). The leading non-infectious cause of death was cardiac failure (9%). Comparison of the characteristics at the TOD between 1990 and 1996 revealed significant differences in mean age (2.1 vs. 9.2 years, P < 0.0001), mean CD4 count index (0.18 vs. 0.02, P < 0.03), mean number of organ/organ system involvement (3.9 vs. 5.9, P < 0.05), percent receiving antiretroviral therapy (33% vs. 70%, P < 0.02), mean number of years receiving antiretroviral therapy (0.88 vs. 3.86 years, P < 0.01), percent receiving P. carinii pneumonia prophylaxis (27% vs. 100%, P < 0.001), percent receiving MAC prophylaxis/therapy (0% vs. 100%, P < 0.0001), and cause of death from P. carinii pneumonia (53% vs. 0%, P < 0.01). CONCLUSIONS: Compared with children who died in 1990, HIV-infected children who died in 1996 were significantly older, more lymphopenic and more likely to have a greater number of organ system involvements and to have received antiviral therapy and antimicrobial prophylaxis. In 1996 no child died of P. carinii pneumonia. In 1996 MAC and P. aeruginosa were the two most important opportunistic infections causing death. These changes in the characteristics at death will warrant review of resources used in treating these children and may be critical in advising parents and care givers about the prognosis of this chronic infection.

Micronutrient and cytokine interaction in congenital pediatric HIV infection.

Malnutrition is a frequent manifestation of HIV infection that has received comparatively little attention despite growing clinical importance with improved treatment and lengthened survival times. Fundamental relationships and mechanisms of HIV viral interaction in nutrient metabolism remain to be established. In an attempt to begin to fill the void of information relative to pediatric HIV infection, we have summarized the extant knowledge with regard to micronutrients and present some of the data from studies performed in our laboratory. Previous studies have shown both that vitamin A deficiency is associated with increased mortality in HIV+ intravenous drug users and that maternal vitamin A deficiency is a risk factor for transmission in congenital exposure. Our most significant finding is that 70% of children congenitally exposed to HIV are vitamin A-deficient in the first months of life compared to age-matched controls whether they are HIV-infected or not. About 25% of our patient population was found to have growth or developmental delay, frequently without other signs of progression and in the presence of an intact T-cell compartment. In addition, we found evidence of cytokine imbalance, specifically elevated plasma levels of TNF which has been implicated in loss of lean body mass. Inflammatory reactions in the mucosa and increased TNF production in association with regional HIV infection may compromise gastrointestinal absorption. Based on the review of the literature and our research findings, it is clear that understanding the interaction between nutrients and both the regional and systemic immune system is vital for intervention and effective nutrient repletion in congenital HIV infection.

Effect of granulocyte-macrophage colony-stimulating factor in experimental visceral leishmaniasis.

GM-CSF induces three effects potentially beneficial in visceral leishmaniasis: blood monocyte mobilization, macrophage activation, and amelioration of granulocytopenia. To determine the experimental role and effect of GM-CSF in this intracellular infection, livers from Leishmania donovani-infected BALB/c mice were tested for GM-CSF mRNA expression and mice were treated with anti-GM-CSF antiserum or GM-CSF. L. donovani infection upregulated hepatic GM-CSF mRNA expression by 10-fold, and anti-GM-CSF treatment exacerbated visceral infection and tripled liver parasite burdens 4 wk after challenge. In euthymic mice with established infection, treatment with 1-5 micrograms/d murine GM-CSF induced three dose-related effects: peripheral blood leukocytosis, preferential accumulation of myelomonocytic cells at visceral foci of infection, and leishmanicidal activity comparable to that achieved by IFN-gamma. These effects were either largely or entirely T cell dependent. Treatment with human GM-CSF also induced anti-leishmanial activity but with little effect on peripheral leukocyte number or tissue myelomonocytic cell influx; human G-CSF stimulated marked peripheral granulocytosis and neutrophil tissue accumulation but induced little antileishmanial effect. These results identify a role for endogenous GM-CSF in the initial host defense response to L. donovani, reemphasize the influxing monocyte as an effector cell, and indicate that GM-CSF can be used as an antileishmanial treatment.

Effector role of blood monocytes in experimental visceral leishmaniasis.

In BALB/c mice, liver granulomas provoked by visceral infection with intracellular Leishmania donovani are rapidly populated by influxing blood monocytes. To determine the host defense effector role of these mononuclear phagocytes, we treated three populations of infected animals with 5C6, an anti-type 3 complement receptor monoclonal antibody (MAb), which inhibits monocyte recruitment into inflamed tissues. In naive BALB/c mice, injections of 5C6 impaired the initial acquisition of antileishmanial resistance and arrested the development of mature liver granulomas. In sensitized mice with established immunity, both resistance to rechallenge and accelerated granuloma formation were similarly inhibited by MAb administration. Finally, in naive mice, 5C6 MAb also abolished the antileishmanial activity induced by treatment with the macrophage-activating lymphokine gamma interferon. Together, these results suggest a key effector role for the influxing blood monocyte in both initial and established antileishmanial defense and granuloma assembly and in the infected liver as the mononuclear phagocyte target for the antimicrobial effects of gamma interferon.

Septic pulmonary embolism complicating a central venous catheter.

Bacteremia is a recognized complication in patients with indwelling central venous catheters. More recently pulmonary embolism in such patients has also been described. Despite abundant clinical experience with these devices, to our knowledge, septic pulmonary embolism has not been reported in adult patients. This case illustrates such a complication.