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LY146032, a cyclic peptide antibiotic active against many Gram-positive bacteria, was compared to methicillin, vancomycin, clindamycin, cefuroxime and gentamicin against methicillin-resistant and methicillin-susceptible strains of Staphylococcus aureus and Staph. epidermidis. LY146032 was uniformly active against clinical isolates of staphylococci, inhibiting 90% of strains of Staph. aureus and Staph. epidermidis at a concentration of 0.5 mg/l. Vancomycin was slightly less active than LY146032 against Staph. aureus and Staph. epidermidis, inhibiting 90% of strains at concentrations of 1.0 and 2.0 mg/l, respectively. All other antibiotics tested were less active than LY146032 or vancomycin against staphylococci. LY146032 was compared to penicillin, ampicillin, vancomycin and chloramphenicol against strains of Streptococcus pneumoniae, group B streptococcus, group D streptococcus (enterococcus) and Listeria monocytogenes and was found to inhibit 90% of the strains at concentrations of 0.25, 1.0, 32.0 and 16.0 mg/l respectively. The combination of LY146032 and chloramphenicol was antagonistic in vitro for one strain each of Staph. aureus and group D streptococcus and showed indifference against other strains of Staph. aureus(2), Staph. epidermidis(2), group D streptococcus(1) and L. monocytogenes(2). LY146032 in combination with gentamicin showed indifference against the same bacteria. On the basis of its in-vitro activity, LY146032 appears to be a promising agent for the treatment of serious community- and hospital-acquired staphylococcal infections. [ABSTRACT FROM AUTHOR]

The pathogenesis of Citrobacter diversus meningitis and brain abscess was studied in infant rats. Two-day-old rats were inoculated intraperitoneally and intranasally with C. diversus. C. diversus strain 4277, lacking the 32,000-molecular-weight outer membrane protein that appears to be a marker for strains causing meningitis in human neonates, was more likely to produce bacteremia, meningitis, and death in rats than was strain 4036, which possesses this outer membrane protein. Strain 4036 was, however, more likely than strain 4277 to produce ventriculitis and brain abscess. In the infant rat, central nervous system involvement by C. diversus begins with bacteremia and leptomeningitis, followed by ventriculitis and direct extension of infection into periventricular brain parenchyma. Large numbers of bacteria persist inside inflammatory cells, an observation suggesting resistance to intraphagocytic killing. Bacterial strain differences, possibly related to the presence of a 32,000-molecular-weight outer membrane protein, may account for histopathologic differences in the brains of infant rats with C. diversus meningitis. [ABSTRACT FROM AUTHOR]

We studied 17 strains of Citrobacter diversus isolated from the cerebrospinal fluid of infants with meningitis and compared these strains with 21 strains isolated from other body sites. The two groups of strains were similar with respect to biotype, piliation, hemolysin production, and resistance to the killing effects of serum. By using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we found that 14 (82%) of 17 strains from cerebrospinal fluid, but only two (10%) of 21 strains isolated from other body sites, possessed a minor outer membrane protein with a molecular weight of 32,000 (P less than .0001). This protein may serve as a marker for strains of C. diversus that are likely to cause meningitis or brain abscess in human neonates. [ABSTRACT FROM AUTHOR]

The authors present their experience with the evaluation and follow-up of 62 patients with primary cysts of the iris, discuss their clinical and pathological features, and propose a simple classification for these lesions. The results suggest that the great majority of primary iris cysts, particularly those which arise from the iris pigment epithelial layers, are stationary lesions which rarely progress or cause visual complications. This finding is contradictory to the belief of certain authorities who stress that many such lesions lead to severe complications, with blindness and loss of the eye. The natural course of primary epithelial cysts differs from that of secondary iris cysts which follow surgical or nonsurgical trauma. The latter lesions do frequently enlarge and lead to severe complications such as inflammation and glaucoma. The major clinical importance of primary iris cysts lies in their similarity to neoplasms of the iris and ciliary body. It is concluded that the great majority of them are ophthalmic curiosities which require no treatment. [ABSTRACT FROM PUBLISHER]

Implementation of HIV care and treatment programs in sub-Saharan Africa is a complex undertaking that requires training of health care providers (HCPs). Many sub-Saharan African countries have introduced training programs to build human resources for health. Evaluation of the ongoing trainings is warranted so that programs can be improved. The purpose of this study was to evaluate Baylor International Pediatric AIDS Initiative's (BIPAI) HCP training program in Swaziland. The specific aims were: (1) to assess coverage and delivery of the training program; and (2) to determine the impact of the training program on HCPs' knowledge about HIV and pediatric practices, attitudes toward HIV/AIDS patients, and self-efficacy to provide antiretroviral therapy (ART). The evaluation was a multimethod design with two types of data collection and analysis: (1) one-group pretest-posttest survey with 101 HCPs; and (2) semi-structured in-depth interviews with seven trainers from Baylor College of Medicine and 16 local HCPs in Swaziland. Quantitative data were analyzed using Stata Statistical Software version 8.2 for descriptive and multivariate analysis while factor analysis was done using Statistical Program for Social Sciences version 14. The transcribed interviews were analyzed using a didactic approach. Process evaluation showed that the training had good coverage, was delivered as intended, and improved as the work progressed. The training program led to a significant increase (p=0.0000) in HCPs' knowledge about HIV/AIDS, ART, and relevant clinical pediatrics practices between pretest (mean 68.7% SD 13.7) and post training (mean 84.0% SD 12.0). The training program also increased trainees' self-efficacy to provide ART and their attitudes toward AIDS patients (p=0.0000 and 0.02, respectively). In conclusion, BIPAI training program in Swaziland had good coverage of all health care facilities and HCPs in Swaziland. The training was effective in imparting knowledge and skills to HCPs and in their attitudes toward HIV/AIDS patients.

Objectives: To evaluate the pharmacokinetics, tolerance, safety and antiviral activity of the HIV protease inhibitor, saquinavir, formulated as soft gelatin capsules (SQV-SGC), given in combination with nucleoside antiretroviral agents (NRTIs) with or without nelfinavir in HIV-infected children., Methods: This was an open label study of HIV-infected children ages 3 to 16 years, conducted in two parts. In Part 1 of the study 14 children were treated orally with SQV-SGC (initially given in three 33-mg/kg doses daily; dosage adjusted to 50 mg/kg three times daily based on initial pharmacokinetics) and two NRTIs. Addition of nelfinavir was permitted for children who did not achieve a predetermined steady state target plasma saquinavir exposure. In Part 2 a new group of 13 children received SQV-SGC (33 mg/kg three times daily) in combination with nelfinavir and one or two NRTIs. Pharmacokinetics were assessed after the first dose and 4 weeks into treatment (steady state). Patients were treated for 72 and 48 weeks in Parts 1 and 2, respectively., Results: Most adverse events were mild; the most commonly reported were diarrhea, abdominal discomfort and headache. Two children were withdrawn from the study because of adverse events (one each of nausea and dysphagia) related to the study treatment. There were no deaths or serious adverse events attributed to the study medication. Steady state saquinavir area under the plasma concentration vs. time curves (AUC24) were 6,210 and 11,010 ng/h/ml for Parts 1 and 2, respectively. Compared with baseline measurements median changes in plasma HIV RNA concentrations were -2.12 log10 copies/ml [5 of 14 (36%) with HIV RNA <50 copies/ml) (Week 72)] and -2.58 log10 copies/ml [8 of 13 (62%) <50 copies/ml) (Week 48)] in Parts 1 and 2, respectively. The median changes in CD4+ lymphocyte count were +292 and +154 cells/microl for Parts 1 and 2, respectively. Genotypic resistance assays revealed a low frequency of saquinavir-associated resistance mutations after 48 weeks of therapy, with only 2 of 27 children having substitutions at positions 48V and/or 90M., Conclusions: Combination therapy with SQV-SGC was well-tolerated and safe in HIV-infected children, and antiviral activity was observed. Saquinavir plasma concentrations were lower than expected, particularly for Part 1 (SQV-SGC plus NRTIs), but addition of nelfinavir increased saquinavir exposures.

The results of the development of dosing guidelines for stavudine in human immunodeficiency virus (HIV)-infected children are summarized. Included in the integrated analyses were 21 and 33 HIV-infected pediatric and adult patients, respectively, from three phase I-II studies. Data for 21 children and 18 adults who received intravenous doses of 0.125 to 2 and 0.5 to 1 mg/kg of body weight, respectively, were used for the determination of dosing guidelines; exposure data for 16 children and 15 adults who received oral doses of 1 to 2 and 0.5 to 1 mg/kg/day, respectively, were used to validate the dosing recommendations for children. Significant relationships were observed between total body clearance (in milliliters per minute) in children and adults combined and demographic parameters of age, body weight, and body surface area (R(2) = 0.77 to 0.80; P = 0.0001). Models of approximated pediatric dose based on clearance values and direct adult exposure yielded a stavudine dosage of 2 mg/kg/day for children of < or =30 kg of body weight and 1 mg/kg/day (adult dose) for children of >30 kg of body weight.

Objective: To evaluate the safety and antiviral and immunologic effects of hydroxyurea given with didanosine (ddI) and/or stavudine (d4T) to symptomatic HIV-infected children., Methods: HIV-infected children with a history of long term nucleoside antiretroviral therapy were treated orally with hydroxyurea (initial dose, 10 to 20 mg/kg once daily; final dose, 30 mg/kg once daily), added to existing therapy that included ddI and/or d4T., Results: Sixteen children were enrolled (mean age, 6.7 years; range, 1.8 to 13.4 years). Antiretroviral therapy used with hydroxyurea included d4T/ddI (12), ddI (2), d4T (1) and d4T/lamivudine (1). Children received between 24 and 48 weeks of therapy, which was well-tolerated. Hydroxyurea was held temporarily during the first month of therapy in 4 cases because of neutropenia; all patients resumed hydroxyurea at full dosage without recurrence of neutropenia. No patient discontinued therapy permanently because of intolerance or toxicity. For the 13 children who completed 48 weeks of study treatment, the mean plasma HIV RNA concentration decreased from 4.6 log10 copies/ml at baseline to 4.2 log10 copies/ml at study Week 48 (P = 0.035, paired t test). Eight of these 13 children experienced a 0.5-log10 copies/ml or greater drop in HIV RNA concentration in the 48 weeks of study treatment. Appreciable changes in CD4+ lymphocyte percentage were not noted., Conclusions: Hydroxyurea, added to existing therapy with ddI and/or d4T, was well-tolerated and safe in HIV-infected children. Evidence of antiviral activity was observed in some cases.

This meta-analysis of 5 large studies of the Pediatric AIDS Clinical Trials Group was undertaken to evaluate the predictive value of antiretroviral treatment-mediated changes in 3 markers of human immunodeficiency virus (HIV) type 1 disease progression-HIV-1 RNA level, CD4 cell count, and CD4 percentage-for weight growth failure, cognitive decline, and survival in HIV-infected children. Proportional hazards models were used to assess the prognostic value of the markers at baseline and after 24 weeks of treatment, with data from 1089 children. Among children receiving nucleoside with or without nonnucleoside reverse-transcriptase inhibitors, higher immunologic and lower virologic markers at baseline and after 24 weeks were significant independent predictors of survival, whereas virologic markers were significant predictors of weight growth and cognitive failure in children >1 year old. The finding of differential age effects on pediatric-specific clinical outcomes emphasizes the need for continued investigation of treatment effects in children.

Purpose: The purpose of this descriptive longitudinal clinical study was to determine primary and permanent dentition caries status in HIV-infected children, and to compare caries status with the CD4 percentage (CD4%) and immune suppression category., Materials and Methods: 73 children up to 9 years of age with vertical HIV transmission were evaluated for caries in the primary dentition at baseline and at 6 month intervals over a 30 month period; while 19 HIV-infected children between 5 and 11 years of age had their permanent dentition evaluated for caries at baseline and at 6 month intervals over a 24 month period. Caries status was also compared with CDC CD4 percentage (> 25%, 15-24%, < 15%), and CDC immune suppression categories (immune suppression: none, moderate, severe). With primary dentition caries, comparisons were made among all children (2-9 yr-olds, N = 73), < 2 yr-olds (N = 28), 2 to 4 yr-olds (N = 20), and 5 to 9 yr-olds (N = 25), and compared with NHANES III data. Caries-free status was also determined., Results: During the 30-month period, there was an almost two-fold increase in primary tooth surface caries for the 2 to 9 year-olds. Caries-free status in the primary dentition declined from 60% at baseline to 37% at the 30-month period. With 5 to 11 years-olds, DMFS and DMFT remained relatively stable, while the proportion of caries-free individuals declined from 72% at baseline to 50% at 18 months. Caries in the primary dentition was increased substantially for those in the low CDC CD4 percentage categories and CDC moderate to severe immune suppression categories., Conclusion: Primary dentition caries status in HIV-infected children is considerably greater than that for the US pediatric population, and increases with decreasing CD4 percentage and moderate to severe immune suppression. HIV-infected children with caries-free primary dentitions are less frequent than in the US pediatric population, and caries-free status decreases with age, lower CD4 percentage and moderate to severe immune suppression.

The use of human immunodeficiency virus (HIV) protease inhibitors in children has lagged behind that in adults because of the lack of suitable pediatric formulations and information on safe and effective dosing regimens. This study was designed to obtain pharmacokinetic information on indinavir, administered to HIV-infected children also receiving therapy with two nucleoside agents, and to explore relationships between pharmacokinetic parameters and anti-HIV effect. Indinavir was initiated at a dose of 500 mg/m(2) every 8 h. Plasma indinavir concentrations were measured every 4 weeks; the dose or dosing interval was adjusted to maintain trough concentrations of > or =0.1 mg/liter. All children were evaluated clinically at baseline and every 4 weeks. Plasma HIV RNA was quantitated at baseline and at weeks 4, 12, and 24. Eighteen children participated in this study. The average daily dose of indinavir was 2,043 mg/m(2); nine children received indinavir at 6-h intervals. Pharmacokinetic characteristics of indinavir (mean +/- standard deviation) were the following: oral clearance, 1.4 +/- 0.5 liters/h/kg; half-life, 1.1 +/- 0.43 h; and trough concentration, 0. 29 +/- 0.32 mg/liter. In nine children that completed 24 weeks of therapy, the baseline-to-week-24 change in HIV RNA level was related to indinavir trough concentration and didanosine area under the curve. This study illustrates the ability to obtain pharmacokinetic information from children during routine clinic visits and to use this information to provide a safeguard against underdosing. The incorporation of pharmacologic knowledge with virologic, immunologic, and behavioral considerations should result in improved clinical outcomes for children infected with HIV.

To assess the prevalence and prognostic significance of the history of oral manifestations in children with human immunodeficiency virus infection (HIV), a cohort study of 73 children with vertical HIV infection was conducted. The study subjects were examined every 6 months for oral manifestations. The period prevalence of oral manifestations ranged from a low of 1% for submandibular enlargement and 3% for hairy leukoplakia to a high of 36% for xerostomia and 51% for cervical lymphadenopathy. The occurrence of oral manifestations did not change significantly over time from 1995 to 1998. Finally, the odds of occurrence of cervical lymphadenopathy, xerostomia, and oral candidiasis were greater among children in whom these manifestations had been diagnosed in the preceding 6-18 months than in children without prior diagnosis. Oral manifestations are significant clinical outcomes in pediatric vertical HIV infection, particularly for children diagnosed previously with an oral manifestation.

Objectives: The aim of this study was to investigate the frequency of viral nucleic acid detection in the myocardium of human immunodeficiency virus (HIV)-infected children to determine whether an association exists with the development of heart disease., Background: As improved medical interventions increase the life expectancy of HIV-infected patients, increased incidences of myocarditis and dilated cardiomyopathy (DCM) are becoming more apparent, even in patients without clinical symptoms., Methods: Myocardial samples were obtained from the postmortem hearts of 32 HIV-infected children and from 32 age-matched controls consisting of patients with structural congenital heart disease and no myocardial inflammation and no cardiac or systemic viral infection. The hearts were examined histologically and analyzed for the presence of viral sequences by polymerase chain reaction (PCR) or reverse transcription-PCR., Results: Myocarditis was detected histologically in 11 of the 32 HIV-infected patients, and borderline myocarditis was diagnosed in another 13 cases. Infiltrates were confined to the epicardium in two additional hearts. Virus sequences were detected by PCR in 11 of these 26 cases (42.3%); adenovirus in 6, CMV in 3 and both adenovirus and CMV in 2. Two cases without infiltrates were also positive for adenovirus: one had congestive heart failure (CHF) and the other adenoviral pneumonia. No other viruses were detected by PCR, including HIV proviral DNA. All control samples were negative for all viruses tested., Conclusions: These data suggest that the presence of viral nucleic acid in the myocardium is common in HIV-infected children, and may relate to the development of myocarditis, DCM or CHF and may contribute to the rapid progression of HIV disease.

Introduction: Large population studies of adult patients suggest an incidence of cytomegalovirus (CMV) retinitis as high as 19% to 20% as a late complication of adult HIV infection. We conducted this prospective study of a large cohort of HIV-infected children to determine the incidence of CMV retinitis in HIV-infected children., Methods: From January 1984 to August 1997, 173 HIV-infected children were followed up for an average of 55.3 months (13-164 months). The patients were seen in the Department of Pediatrics at least once every 6 months. Ophthalmologic examinations were initiated when a patient's CD4 count dropped below 50 or sooner if required for ophthalmologic or other indications. Ophthalmologic examination was then repeated every 6 months., Results: A total of 116 (67%) of 173 patients underwent ophthalmologic examination. Four (3.4%) of 116 patients had CMV retinitis at a mean time of 17.3 months (8-38 months) after their CD4 counts dropped below 20. None of the 4 patients with CMV retinitis had subjective visual complaints despite advanced retinitis. Three patients had bilateral and 1 patient had unilateral CMV retinitis., Conclusions: CMV retinitis occurred infrequently in HIV-infected pediatric patients and was diagnosed only in patients with a CD4 count below 20. Routine ophthalmologic screening examinations may not be necessary in pediatric patients until the CD4 count is below 20. Because children may not complain of decreased vision, at-risk children should undergo frequent ophthalmologic examination.

Nineteen children with human immunodeficiency virus (HIV) infection were treated with recombinant human gamma interferon (rIFN-gamma) (50 microg/m2 subcutaneously three times each week during weeks 1 through 12 and 100 microg/m2 subcutaneously three times each week during weeks 13 through 24) in a phase I/II clinical trial. All children continued to receive previously prescribed therapy with oral zidovudine or didanosine. Children were assessed clinically and with laboratory studies during 24 weeks of study treatment and for 12 weeks after completion of rIFN-gamma therapy. In general, rIFN-gamma therapy was well tolerated. There were two clinical or laboratory adverse events thought to be possibly or probably study drug associated. One child developed acute pancreatitis; another child developed granulocytopenia. Median CD4(+)-lymphocyte counts and plasma HIV RNA concentrations did not change significantly during therapy. In vitro neutrophil bactericidal activity against Staphylococcus aureus and superoxide production were not significantly affected by rIFN-gamma therapy. We conclude that rIFN-gamma therapy in HIV-infected children receiving single-agent antiretroviral therapy is safe and does not produce consistent changes in CD4(+)-lymphocyte count, plasma HIV RNA concentration, or in vitro neutrophil function.

Objectives: To evaluate the safety, tolerance, and antiviral activity of combination therapy with stavudine (d4T) plus didanosine (ddI) in symptomatic human immunodeficiency virus (HIV)-infected children., Methods: The study enrolled HIV-infected children who successfully completed Pediatric AIDS Clinical Trials Group (PACTG) protocol 240 (d4T versus zidovudine [ZDV] monotherapy) without disease progression or who had received ZDV monotherapy by prescription for at least the preceding 6 months. Children who had received d4T monotherapy in PACTG 240 were assigned to treatment with d4T plus ddI (arm 1). Children who had received ZDV monotherapy in PACTG 240 or by prescription were randomized in a double-blind manner to treatment with either d4T alone (arm 2) or d4T plus ddI (arm 3). Patients were followed for 48 weeks each., Results: A total of 108 children were enrolled. The mean age was 5.0 years (range, 1. 6 to 11.5 years), with mean baseline plasma HIV RNA concentration and CD4(+) lymphocyte count of 4.6 log10 copies/mL (range, 2.6 to 5. 9 log10 copies/mL) and 819 cells/microL (range, 8 to 3431 cells/microL), respectively. Both d4T monotherapy and d4T plus ddI combination therapy were well-tolerated, with 96 (89%) patients completing 48 weeks of study treatment. Plasma HIV RNA concentrations showed larger average declines in arm 3 compared with arm 2 at study week 12 (0.49 vs 0.18 log10 copies/mL, respectively); these average declines were maintained through week 48 (0.51 vs 0.17 log10 copies/mL, respectively). Fewer than 8% of the patients in any of the treatment arms had plasma HIV RNA concentrations below the limit of quantification (200 copies/mL) at any time point., Conclusions: Combination therapy with d4T plus ddI is safe and well-tolerated in HIV-infected children, producing durable, but incomplete, suppression of virus replication. This combination of nucleoside antiretroviral agents may provide a valuable backbone to protease inhibitor-containing treatment regimens for HIV-infected children.

Objectives: To evaluate the pharmacokinetic features, safety, and tolerance of abacavir, given alone and in combination with other nucleoside antiretroviral agents, in symptomatic human immunodeficiency virus (HIV)-infected children., Methods: HIV-infected children discontinued prior antiretroviral therapy and were given abacavir orally, 4 mg/kg every 12 hours for 6 weeks, followed by 8 mg/kg every 12 hours for 6 weeks (n = 39); or 8 mg/kg every 12 hours for 12 weeks (n = 8). Children then were randomized to receive a second nucleoside antiretroviral agent (zidovudine, stavudine, didanosine, or lamivudine), plus abacavir. Pharmacokinetics, safety, tolerance, CD4(+) lymphocyte counts, and plasma HIV RNA concentrations were evaluated., Results: At a dose of 8 mg/kg every 12 hours, area under the plasma concentration-versus-time curves and plasma half-life values were comparable with those reported for adults receiving abacavir at a dose of 300 mg twice daily. One case each of hypersensitivity reaction and peripheral neuropathy occurred during abacavir monotherapy. Three children experienced neutropenia while receiving abacavir in combination with another antiretroviral agent. Mean CD4(+) lymphocyte count and plasma HIV RNA concentration did not change when prior antiretroviral therapy was changed to abacavir monotherapy., Conclusions: Abacavir therapy is associated with good short-term tolerance and safety in HIV-infected children. Phase III studies are in progress to assess the antiviral activity of abacavir in children and adults.

Abacavir (formerly 1592U89) is a potent 2'-deoxyguanosine analog reverse transcriptase inhibitor that has been demonstrated to have a favorable safety profile in initial clinical trials with adults with human immunodeficiency virus (HIV) type 1 infection. A phase I study was conducted to evaluate the pharmacokinetics and safety of abacavir following the administration of two single oral doses (4 and 8 mg/kg of body weight) to 22 HIV-infected children ages 3 months to 13 years. Plasma was collected for analysis at predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, and 8 h after the administration of each dose. Plasma abacavir concentrations were determined by high-performance liquid chromatography, and data were analyzed by noncompartmental methods. Abacavir was well tolerated by all subjects. The single abacavir-related adverse event was rash, which occurred in 2 of 22 subjects. After administration of the oral solution, abacavir was rapidly absorbed, with the time to the peak concentration in plasma occurring within 1.5 h postdosing. Pharmacokinetic parameter estimates were comparable among the different age groups for each dose level. The mean maximum concentration in plasma (Cmax) and the mean area under the curve from time zero to infinity (AUC0-infinity) increased by 16 and 45% more than predicted, respectively, as the abacavir dose was doubled from 4 to 8 mg/kg (Cmax increased from 1.69 to 3.94 micrograms/ml, and AUC0-infinity increased from 2.82 to 8.09 micrograms.h/ml). Abacavir was rapidly eliminated, with a mean elimination half-life of 0.98 to 1.13 h. The mean apparent clearance from plasma decreased from 27.35 to 18.88 ml/min/kg as the dose increased. Neither body surface area nor creatinine clearance were correlated with pharmacokinetic estimates at either dose. The extent of exposure to abacavir appears to be slightly lower in children than in adults, with the comparable unit doses being based on body weight. In conclusion, this study showed that abacavir is safe and well tolerated in children when it is administered as a single oral dose of 4 or 8 mg/kg.

Although the character of acquired immunodeficiency syndrome is changing into a chronic illness, it is estimated that by the end of this century, 80 000 children and adolescents in the United States will be orphaned by parental death caused by human immunodeficiency virus infection. Plans for these children need to be made to ensure not only a stable, consistent environment that provides love and nurturing, but also the medical and social interventions necessary to cope with the tragic loss. Pediatricians should become aware of local laws and community resources and initiate discussion early in the course of parental illness to facilitate planning for the future care and custody of the children. States need to adopt laws and regulations that provide flexible approaches to guardianship and placement of children orphaned by acquired immunodeficiency syndrome.

Acquisition of saliva for biologic, immunologic and chemical analyses has been extremely difficult in infants and young children due to lack of cooperation and motor skills necessary for expectorating adequately. The purpose of this study was to investigate a technique for obtaining satisfactory quantities of whole, unstimulated saliva in the typical dental operatory setting for cytologic, microbiologic and viral evaluation, while requiring minimal cooperation and motor skills from pediatric patients. A low vacuum-assisted aspiration device was utilized to obtain samples from infants and children who were at risk for vertically acquired HIV-infection (age-range 6 mos to 8 yrs). Adequate saliva samples were collected in 175 of 196 (89 percent) attempts in 88 of 89 (99 percent) children (2.3 samples/child). Saliva was not obtained in twenty-one attempts primarily due to xerostomia (62.5 percent). Saliva sample volume obtained was variable, ranging from 1.2 to 3.6 mls with a collection time of approximately three to five minutes. Cell block preparations were made from the saliva, which allowed for cytologic evaluation of sloughed superficial squamous cells, evaluation of oral flora, and detection of yeast and hyphal fungal forms. Adequate volumes of supernate were also available for microbiologic and viral cultures, immunologic studies and PCR study for various viral agents shed in the saliva. Use of a vacuum-assisted collection device for whole unstimulated saliva in infants and young children in the dental operatory setting provides adequate saliva for multiple analyses, which may provide information regarding HIV disease status and early diagnosis of opportunistic infections.

The genetic diversity and molecular epidemiology of Mycobacterium avium complex (MAC) infections in children with and without human immunodeficiency virus (HIV) infection were evaluated. Isolates recovered from 136 children were subtyped by sequence analysis of a 360-bp region of the gene (hsp65) encoding a 65-kDa heat-shock protein. Twenty-one distinct hsp65 alleles were identified. On the basis of hsp65 genotype, 6 isolates were not MAC organisms. Of the remaining 130 samples, 61% were M. avium, 37% were Mycobacterium intracellulare, and 2% were species nonspecific MAC. Eighty-eight percent of the isolates obtained from HIV-infected children were M. avium. In contrast, only 38% of the isolates obtained from children without HIV infection were M. avium (chi2 test, P < .001). M. avium isolates were further subtyped by Southern blot analysis with insertion element IS1245. Taken together, no evidence for a single clonal M. avium strain causing infection was detected.

Lautropia mirabilis, a pleomorphic, motile, gram-negative coccus, has been isolated from the oral cavities of 32 of 60 (53.3%) children infected with human immunodeficiency virus (HIV) and 3 of 25 (12.0%) HIV-uninfected controls; the association of L. mirabilis isolation with HIV infection is significant (P < 0.001). All children in the study, both HIV-infected children and controls, were born to HIV-infected mothers. The presence of this bacterium was not associated with clinical disease in these children. The HIV-infected children with L. mirabilis did not differ from the HIV-infected children without L. mirabilis in immunological status, clinical status, or systemic medications. The role of HIV infection itself or concomitant factors in the establishment of L. mirabilis in the oral cavity remains to be elucidated.

Purpose: Fungal infections in HIV-infected individuals are associated with advancement of disease. In pediatric HIV infection, symptomatic children have a significantly higher incidence of clinical candidiasis and persistent drug-resistant candidiasis than do asymptomatic HIV-infected children. The purpose of this preliminary cytologic study was to determine the prevalence of fungal organisms in whole unstimulated saliva from children with vertically acquired HIV infection., Methods: The subjects included 27 HIV-infected and 11 HIV-exposed, but uninfected, children. Whole unstimulated saliva was obtained for cytologic evaluation (hematoxylin and eosin, silver stains) with selected samples evaluated by electron microscopy., Results: Yeast and hyphae were identified cytologically in 19% of HIV-infected (22% symptomatic HIV-infected, 11% asymptomatic HIV-infected) and 9% of HIV-exposed, but uninfected, children. Fungal organisms were found more frequently in HIV-infected with moderate (18%) and severe (27%) suppression. Fungi were more frequent with antiretroviral therapy (22%) vs no antiretroviral therapy (0%) and no antifungal therapy (20%) vs. antifungal therapy (7%). Yeast and hyphal fungal forms are more prevalent in symptomatic HIV-infection with moderate and severe suppression, and those receiving antiretroviral agents, but no antifungal medications., Conclusion: Fungal organisms in the saliva may reflect oral carriage or mucosal colonization, which may influence the development of clinically significant candidiasis in these immunocompromised children.

Twelve children infected with the human immunodeficiency virus were treated orally with indinavir, stavudine, plus didanosine for 12 to 48 weeks. Therapy was limited in some cases by nonadherence, intolerance, toxicity, and virologic failure. Marked increases in CD4+ lymphocyte counts and decreases in plasma human immunodeficiency virus RNA concentrations suggest that the regimen has potent antiviral activity.