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* Abbreviations: COVID-19 — : coronavirus disease 2019 nAb — : neutralizing antibody SARS-CoV-2 — : severe acute respiratory syndrome coronavirus 2 After having coronavirus disease 2019 (COVID-19), patients develop a humoral immune response thought to protect against reinfection, but antibody levels can decline over time. Understanding how long antibody levels remain high enough to prevent infection is important in understanding, absent vaccination, whether children may be vulnerable to COVID-19 and in modeling how COVID-19 spreads through the population. The levels of antibodies capable of neutralizing the virus (neutralizing antibodies [nAbs]) provide a direct marker of a protective humoral immune response. The nAbs can be measured directly by determining how well a patient’s serum inactivates virus when a known amount of virus is placed on cells in tissue culture, which is known as a plaque reduction neutralization test. The remarkably safe and effective approved COVID-19 vaccines elicit potent antibody responses against portions of the virus mediating attachment to host cells and viral entry, the spike protein and its receptor-binding domain. The concentration of antibodies a patient has against spike … Address correspondence to: Andrea T. Cruz, Department of Pediatrics, Baylor College of Medicine, 6621 Fannin St, Suite A2210, Houston, TX 77030. E-mail: acruz{at}bcm.edu

Multisystem inflammatory syndrome in children (MIS-C) is a serious, sometimes life-threatening late complication of coronavirus disease 2019 (COVID-19) with multiorgan involvement and evidence of immune activation. The pathogenesis of MIS-C is not known, nor is the pathogenesis of the severe organ damage that is the hallmark of MIS-C. Human herpesvirus 6 (HHV-6), the virus responsible for roseola, is a ubiquitous herpesvirus that causes close to universal infection by the age of 3 years. HHV-6 remains latent for life and can be activated during inflammatory states, by other viruses, and by host cell apoptosis. HHV-6 has been associated with end-organ diseases, including hepatitis, carditis, and encephalitis. In addition, ∼1% of people have inherited chromosomally integrated human herpesvirus 6 (iciHHV-6), which is HHV-6 that has been integrated into chromosomal telomeric regions and is transmitted through the germ line. iciHHV-6 can be reactivated and has been associated with altered immune responses. We report here a case of MIS-C in which an initial high HHV-6 DNA polymerase chain reaction viral load assay prompted testing for iciHHV-6, which yielded a positive result. Additional research may be warranted to determine if iciHHV-6 is commonly observed in patients with MIS-C and, if so, whether it may play a part in MIS-C pathogenesis.

* Abbreviations: COVID-19 — : coronavirus disease 2019 MIS-C — : multisystem inflammatory syndrome in children RBD — : receptor-binding domain S — : severe acute respiratory syndrome coronavirus 2 spike protein SARS-Co-V-2 — : severe acute respiratory syndrome coronavirus 2 Coronavirus disease 2019 (COVID-19) is arguably the most socially and economically disruptive pandemic since the 1918 influenza pandemic. Although pediatric COVID-19 shares features with the adult disease, there are several differences. Children produce virus in amounts at least equal to adults, if not higher,1 and can transmit the virus, just as adults can.2 School-aged children are generally less-severely affected than infants or adults, but some children without significant underlying disease become ill or die in a disease process analogous to the one most commonly seen in adults: severe pulmonary disease and respiratory failure.3–6 Children and adults appear to have different humoral immune responses to COVID-19.7 A small fraction of children with COVID-19 experience a hyperinflammatory process,8–13 termed multisystem inflammatory syndrome in children (MIS-C) in the United States, with features distinct from Kawasaki disease.14 This case definition includes ≥2 of these symptoms: rash, conjunctivitis, or mucocutaneous inflammation; hypotension; cardiac disease; coagulopathy; or acute gastrointestinal problems.15 MIS-C, which is not correlated with viral load levels, typically appears some time after initial infection.13 MIS-C’s incidence is difficult to determine, given the high rate of asymptomatic infection.12 Adults with COVID-19 also can experience inflammatory disorders: coagulopathies, vasculitis, cardiomyositis, and neuroinflammatory processes.16–18 That the most effective therapy to reduce mortality in adults with severe COVID-19 yet established is an immune suppressant, dexamethasone,19 reveals the importance of inflammatory and immune-mediated pathologies. In this issue of … Address correspondence to Steven Zeichner, MD, PhD, Department of Pediatrics, University of Virginia, Box 801349, Charlottesville, VA 22908. E-mail: zeichner{at}virginia.edu

* Abbreviation: COVID-19 — : coronavirus disease of 2019 The impact of the coronavirus disease of 2019 (COVID-19), which is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2,1 has been widespread, with >500 000 cases diagnosed in >170 countries since the virus was identified in January 2020.2 The preliminary data have been focused on severe respiratory manifestations, which are seen predominantly in adults, with scant initial data on the burden of COVID-19 in children.3 We, therefore, read with interest the findings of Dong et al,4 who reported in this issue of Pediatrics a series of >2000 children with suspected or confirmed COVID-19. The authors found that 4% of virologically confirmed cases had asymptomatic infection, and this rate almost certainly understates the true rate of asymptomatic infection because many children who are asymptomatic are unlikely to be tested. Among children who were symptomatic, 5% had dyspnea or hypoxemia (a substantially lower percentage than what has been reported for adults3), and 0.6% progressed to acute respiratory distress syndrome or multiorgan system dysfunction (a rate that is also lower than that seen in adults). Preschool-aged children and infants were more likely than older children to have severe clinical manifestations. There are several salient points … Address correspondence to Andrea T. Cruz, MD, MPH, Department of Pediatrics, Baylor College of Medicine, 6621 Fannin St, Suite A2210, Houston, TX 77030. E-mail: acruz{at}bcm.edu

A 16-year-old girl presented to the emergency department with intermittent fevers and worsening abdominal pain of 5 weeks duration. She had a history of travel to a less developed country and exposure to possible infectious diseases. Abdominal imaging and blood tests revealed diffuse mesenteric lymphadenopathy, elevated transaminases, and elevation of inflammatory markers. Gastroesophageal and colon endoscopies revealed gastric ulcers, and the patient was discharged with a presumptive diagnosis of systemic juvenile idiopathic arthritis given the lymphadenopathy seen on imaging, serositis, sacroiliac joint stiffness noted on physical examination, and pain relief with celecoxib. She presented again 4 days later with worsening abdominal tenderness, elevated transaminases, and new-onset abdominal distention. Tissue biopsy yielded the diagnosis and directed appropriate treatment.

Background/objectives Atopic dermatitis (AD) is a common chronic inflammatory skin condition associated with high transepidermal water loss, high skin pH, and Staphylococcus aureus skin colonization. The treatment of AD with bath additives remains highly debated. Recent evidence suggests that dilute apple cider vinegar (ACV) may improve skin barrier integrity in AD, but its safety and efficacy are not well studied. This pilot split-arm study analyzed the effect of dilute apple cider vinegar soaks on skin barrier integrity in patients with atopic dermatitis as measured by skin transepidermal water loss and skin pH. Methods A total of 22 subjects (11 AD and 11 healthy controls) were enrolled. Subjects soaked both of their forearms for 14 days, with one arm in dilute ACV (0.5% acetic acid) and the other in water 10 minutes daily. Transepidermal water loss and pH were measured pre- and post-treatment. Results In both groups, transepidermal water loss increased and pH decreased at 0 minutes post-ACV treatment, but these effects were not sustained at 60 minutes. In total, 72.7% (16/22) of subjects reported mild side effects from ACV with improvement after discontinuing the soaks. Conclusions Dilute ACV soaks have no significant effect on skin barrier integrity but caused skin irritation in a majority of subjects. Study limitations include analysis of a single brand, dilution, and application of ACV. Future studies are needed to explore whether lower concentrations of ACV soaks or other applications such as a leave-on acidic ointment could improve skin barrier integrity in a safe, nonirritating way.

Short bowel syndrome (SBS) presents an increasing problem in pediatrics. SBS often results from surgical resection of necrotic bowel following necrotizing enterocolitis or treatment of anatomic gastrointestinal defects. SBS is associated with significant morbidity and mortality, and creates substantial burdens for patients, families, and the health system. Recent reports have demonstrated that the fecal microbiome of children with SBS is significantly different from healthy control and severe intestinal microbial imbalances is associated with poor growth. We hypothesized that children with SBS and adverse clinical features such as PN dependent, shorter bowel length and lack of ileocecal valve would demonstrate more gut dysbiosis compare with the SBS non-PN dependent. An improved understanding of SBS pathogenesis would enhance management and potentially suggest new interventions. We studied microbial communities of SBS and control non-SBS patients from the jejunum, obtained endoscopically or by ostomy aspiration, and stool. We enrolled SBS patients who did and did not require parenteral nutrition (PN), as a surrogate marker for the seriousness of their disease. We studied the microbiota using high-throughput DNA sequencing of 16S rRNA genes and statistical analyses. We found that microbial diversity was significantly greater in jejunal aspirate than in stool samples in SBS patients, unlike non-SBS patients; that SBS patients receiving enteral feeds had greater diversity, and that SBS patients on PN and enteral feeds had lower differences in diversity in jejunal vs. stool samples. We found a trend toward increased diversity in patients with an intact ileocecal valve, and found that certain taxa were more abundant in the certain sample types, and in SBS patients vs. non-SBS patients. SBS patients have lower microbial diversity, especially patients with more severe disease, patients requiring PN, and those lacking an ileocecal valve. SBS patients, particularly those with more complex characteristics, exhibit differences in their intestinal microbiota. Particular individual taxa were over- and under-represented in patients with more unfavorable disease. While diminished diversity and alterations in microbiota composition are likely consequences of SBS, future efforts aimed at increasing microbial diversity and interventions targeting specific microbiota characteristics might constitute a testable approach to ameliorate some clinical SBS clinical consequences.

Introduction Atopic dermatitis is a common skin disease characterized by altered cutaneous immunity in which patients often exhibit lower skin microbiota diversity compared to healthy skin and are prone to colonization by Staphylococcus aureus. Apple cider vinegar has been shown to have antibacterial effects; however, its effects on the skin microbiome have not previously been well-described. Objectives We aimed to examine the effects of topical dilute apple cider vinegar soaks on Staphylococcus aureus abundance, skin bacterial microbiome composition, and skin bacterial microbiome diversity in atopic dermatitis participants compared to healthy skin. Methods Eleven subjects with atopic dermatitis and 11 healthy controls were enrolled in this randomized, non-blinded, single-institution, split-arm pilot study. Subjects soaked one forearm in dilute apple cider vinegar (0.5% acetic acid) and the other forearm in tap water for 10 minutes daily. Skin bacteria samples were collected from subjects’ volar forearms before and after 14 days of treatment. 16S sequencing was used to analyze Staphylococcus aureus abundance and skin bacterial microbiome composition, and alpha diversity of microbiota were determined using Shannon diversity index. Results There was no difference in skin bacterial microbiome in atopic dermatitis subjects after 2 weeks of daily water or apple cider vinegar treatments (p = 0.056 and p = 0.22, respectively), or in mean abundance of S. aureus on apple cider vinegar-treated forearms (p = 0.60). At 2 weeks, the skin bacterial microbiomes of healthy control subjects were not significantly different from the skin bacterial microbiome of atopic dermatitis subjects (p = 0.14, 0.21, 0.12, and 0.05). Conclusions Our results suggest that daily soaks in 0.5% apple cider vinegar are not an effective method of altering the skin bacterial microbiome in atopic dermatitis. Further studies are needed to explore the effects of different concentrations of apple cider vinegar on skin microflora and disease severity. Trial number UVA IRB-HSR #19906.

Virologic response to highly active antiretroviral therapy (HAART) treatment of human immunodeficiency virus (HIV) infection depends on viral sensitivity to antiretrovirals (ARV’s) and excellent medication adherence. Adolescents with vertically-acquired HIV may require complicated regimens due to significant treatment experience and often have poor medication adherence. A retrospective chart review identified five adolescents with vertically acquired HIV and plasma HIV viral load rebound or nonresponse on a stable HAART regimen followed by a period of directly observed therapy (DOT) in a clinic or hospital setting with serial viral load measurements. Four subjects had a virologic response (mean decline 1.15 log) after DOT. A response to HAART can be seen despite ARV resistance using DOT, and treatment-experienced patients seemingly unresponsive to HAART may be non-adherent even with reassuring adherence measures. A period of clinic-monitored DOT may allow diagnosis of non-adherence, discussion of medication barriers and avoidance of unnecessary medication changes.

We examined 28 children with HIV-1 infection who were not responding to existing antiviral regimens and were enrolled into clinical trials conducted at the National Cancer Institute to receive salvage therapy. In 3 of the 28 patients (10.7%), the Q151M complex amino acid substitutions were identified. The three patients had received nucleoside reverse transcriptase inhibitor (NRTI) monotherapy and/or combination regimens with multiple NRTIs for 4.3-8.6 years prior to the study. Recombinant infectious clones generated by incorporating the RT-encoding region of HIV-1 isolated from patients' plasma samples were highly resistant to zidovudine, didanosine and stavudine, while they were moderately resistant to lamivudine and tenofovir disoproxil fumarate (TDF). TDF-containing regimens reduced HIV-1 viremia in two of the three children carrying the Q151M complex. These data suggest that the Q151M could be prevalent in pediatric patients with long-term NRTI monotherapy and/or dual NRTI regimens and that HAART regimens containing TDF may be meritorious in such patients.

The oral microbial community (microbiota) plays a critical role in human health and disease. Alterations in the oral microbiota may be associated with disorders such as gingivitis, periodontitis, childhood caries, alveolar osteitis, oral candidiasis and endodontic infections. In the immunosuppressed population, the spectrum of potential oral disease is even broader, encompassing candidiasis, necrotizing gingivitis, parotid gland enlargement, Kaposi’s sarcoma, oral warts and other diseases. Here, we used 454 pyrosequencing of bacterial 16S rRNA genes to examine the oral microbiome of saliva, mucosal and tooth samples from HIV-positive and negative children. Patient demographics and clinical characteristics were collected from a cross-section of patients undergoing routine dental care. Multiple specimens from different sampling sites in the mouth were collected for each patient. The goal of the study was to observe the potential diversity of the oral microbiota among individual patients, sample locations, HIV status and various dental characteristics. We found that there were significant differences in the microbiome among the enrolled patients, and between sampling locations. The analysis was complicated by uneven enrollment in the patient cohorts, with only five HIV-negative patients enrolled in the study and by the rapid improvement in the health of HIV-infected children between the time the study was conceived and completed. The generally good oral health of the HIV-negative patients limited the number of dental plaque samples that could be collected. We did not identify significant differences between well-controlled HIV-positive patients and HIV-negative controls, suggesting that well-controlled HIV-positive patients essentially harbor similar oral flora compared to patients without HIV. Nor were significant differences in the oral microbiota identified between different teeth or with different dental characteristics. Additional studies are needed to better characterize the oral microbiome in children and those with poorly-controlled HIV infections.

Objective. To characterize the type and frequency of biochemical lipid abnormalities and physical changes in body composition associated with the use of protease inhibitor (PI)-containing antiretroviral therapy among human immunodeficiency virus-infected children treated for up to 6 years. Methods. A retrospective study of human immunodeficiency virus-infected pediatric patients enrolled in research protocols between August 1995 and December 2001 was performed. All patients who had received a PI for ≥2 years as part of their investigational antiretroviral treatment regimens during the study period were eligible. Of the 110 patients identified as having received PI therapy, 94 met the study criteria. Results. Of the 94 patients evaluated, 9 patients (10%) developed fat redistribution as well as dyslipidemia, 49 patients (52%) developed dyslipidemia without associated physical changes, and 36 patients (38%) exhibited no elevation of lipid levels or physical signs of fat redistribution. For all 9 patients with fat redistribution, the onset of the physical changes was closely associated with changes during pubertal development. Fat redistribution was also associated with lower viral loads and higher, more sustained levels of dyslipidemia. The onset of dyslipidemia and fat redistribution peaked between 10 and 15 years of age. Conclusion. Among pediatric patients receiving PI therapy, there seems to be an age range in which children are at greater risk of developing hypercholesterolemia and subsequent fat redistribution, suggesting that unidentified physiologic changes associated with puberty may predispose pediatric patients treated with PI therapy to developing lipodystrophy.

Two children (ages 12 and 13 years) with transfusion-acquired human immunodeficiency virus (HIV) infection presented with facial pain and rhinorrhea. Radiographic imaging showed extensive paranasal sinus disease, presumed to be bacterial sinusitis, and the patients were treated with broad-spectrum oral antibiotics. Both patients were unresponsive to oral agents and were switched to intravenous antibiotics. Despite aggressive antimicrobial therapy, one patient (case 1) developed increased periorbital swelling and proptosis, and the other patient (case 2) developed symptoms of nasopharyngeal obstruction. Repeat imaging showed progression of the infiltrative process extending from the paranasal sinuses into the orbit (case 1), and nasopharynx (case 2). Surgical exploration and tissue biopsies were performed on both patients and the histopathology was consistent with Burkitt's/Burkitt's-like lymphoma. Combination systemic and intrathecal chemotherapy resulted in a complete remission in both patients. These reports illustrate the fact that Burkitt's/Burkitt's-like lymphoma in the paranasal sinuses may initially masquerade as an acute bacterial sinusitis. The ability of the tumor to extend rapidly from the sinuses into the orbit and nasopharynx reinforces the importance of early diagnosis and treatment. Burkitt's/Burkitt's-like lymphoma in the paranasal sinuses has not been previously described in HIV-infected children.

5 of 6 children infected with human immunodeficiency virus (HIV) receiving Tenofovir disoproxil fumarate (TDF) experienced absolute decreases in bone mineral density (BMD). 2 pre-pubertal subjects experienced >6% BMD decreases. 1 subject was the smallest child and experienced a 27% decrease, necessitating withdrawal of TDF. Subsequently, her BMD recovered. Monitoring of children infected with HIV who require treatment with TDF is warranted.

OBJECTIVE. Tenofovir disoproxil fumarate, a nucleotide analog HIV reverse transcriptase inhibitor with demonstrated activity against nucleoside-resistant HIV, is approved for use in adults but not children. Metabolic bone abnormalities have been seen in young animals given high-dose tenofovir and HIV-infected adults that were treated with oral tenofovir disoproxil fumarate. However, tenofovir disoproxil fumarate is being used in children despite a lack of bone safety data. We hypothesized that, given the higher rate of bone turnover that is associated with normal skeletal growth, the potential for TDF-related bone toxicity may be greater in children than in adults. METHODS. Fifteen highly antiretroviral-experienced HIV-infected children who were 8 to 16 years of age (mean ± SD: 12 ± 2) and required a change in therapy received tenofovir disoproxil fumarate 175 to 300 mg/m2 per day (adult dose equivalent) as part of highly active antiretroviral therapy for up to 96 weeks. Bone mineral density of the lumbar spine, femoral neck, and total hip by dual-energy x-ray absorptiometry and blood and urine markers of bone metabolism were measured at 0, 24, 48, 72, and 96 weeks. RESULTS. Median z score (SD score compared with age, gender, and ethnicity-matched control subjects) of the lumbar spine, femoral neck, and total hip were decreased from baseline at 24 weeks and 48 weeks and then stabilized. Lumbar spine bone mineral apparent density (which estimates volumetric bone mineral density independent of bone size) z scores also decreased at 24 weeks. Absolute decreases in bone mineral density were observed in 6 children; the mean age of these children was significantly younger than the bone mineral density stable group (10.2 ± 1.1 vs 13.2 ± 1.8 years). The change in lumbar spine bone mineral density correlated with decreases in HIV plasma RNA during treatment. Metabolic markers of bone formation and resorption were variable. Two children in whom tenofovir disoproxil fumarate was discontinued because of bone loss that exceeded protocol allowances demonstrated partial or complete recovery of bone mineral density by 96 weeks. CONCLUSIONS. Tenofovir disoproxil fumarate use in children seems to be associated with decreases in bone mineral density that, in some children, stabilize after 24 weeks. Increases in bone markers and calcium excretion suggest that tenofovir disoproxil fumarate may stimulate bone resorption. Bone turnover is higher in children than in older adolescents and adults because of skeletal growth, potentially explaining the greater effect seen in young children. Decreases in bone mineral density correlate with decreases in viral load and young age, suggesting that young responders may be at greater risk for bone toxicity.

Objectives. Highly active antiretroviral therapy has altered the course of HIV infection among children, but new antiretroviral agents are needed for treatment-experienced children with drug-resistant virus. Tenofovir disoproxil fumarate (DF) is a promising agent for use in pediatric salvage therapy, because of its tolerability, efficacy, and resistance profile. We designed this study to provide preliminary pediatric safety and dosing information on tenofovir DF, while also providing potentially efficacious salvage therapy for heavily treatment-experienced, HIV-infected children.Methods. Tenofovir DF, alone and in combination with optimized background antiretroviral regimens, was studied among 18 HIV-infected children (age range: 8.3–16.2 years) who had progressive disease with ≥2 prior antiretroviral regimens, in a single-center, open-label trial. Tenofovir DF monotherapy for 6 days was followed by the addition of individualized antiretroviral regimens. Subjects were monitored with HIV RNA reverse transcription-polymerase chain reaction, flow cytometry, and routine laboratory studies; monitoring for bone toxicity included measurement of lumbar spine bone mineral density (BMD) with dual-energy x-ray absorptiometry. Subjects were monitored through 48 weeks.Results. Two subjects developed grade 3 elevated hepatic transaminase levels during monotherapy and were removed from the study. The remaining 16 subjects had a median of 4 antiretroviral agents (range: 3–5 agents) added to tenofovir DF. HIV plasma RNA levels decreased from a median pretreatment level of 5.4 log10 copies per mL (range: 4.1–5.9 log10 copies per mL) to 4.21 log10 copies per mL at week 48 (n = 15), with 6 subjects having 6% decrease in BMD for 5 of 15 subjects evaluated at week 48, necessitating the discontinuation of tenofovir DF therapy for 2; all 5 subjects experienced >2 log10 copies per mL decreases in HIV plasma RNA levels.Conclusions. Tenofovir DF-containing, individualized, highly active antiretroviral therapy regimens were well tolerated and effective among heavily treatment-experienced, HIV-infected children. Loss of BMD may limit tenofovir DF use among prepubertal patients.

Tenofovir disoproxil fumarate (DF) is a potent nucleotide analog reverse transcriptase inhibitor approved for the treatment of human immunodeficiency virus (HIV)-infected adults. The single-dose and steady-state pharmacokinetics of tenofovir were evaluated following administration of tenofovir DF in treatment-experienced HIV-infected children requiring a change in antiretroviral therapy. Using increments of tenofovir DF 75-mg tablets, the target dose was 175 mg/m 2 ; the median administered dose was 208 mg/m 2 . Single-dose pharmacokinetics were evaluated in 18 subjects, and the geometric mean area under the concentration-time curve fro m0ht o (AUC0‐) was 2,150 ng h/ml and the geometric mean maximum concentration (Cmax) was 266 ng/ml. Subsequently, other antiretrovirals were added to each patient’s regimen based upon treatment history and baseline viral resistance results. Steady-state pharmacokinetics were evaluated in 16 subjects at week 4. The steady-state, geometric mean AUC for the 24-h dosing interval was 2,920 ng h/ml and was significantly higher than the AUC0‐ after the first dose (P 0.0004). The geometric mean Cmax at steady state was 302 ng/ml. Tenofovir DF was generally very well tolerated. Steady-state tenofovir exposures in children receiving tenofovir DF-containing combination antiretroviral therapy approached values seen in HIV-infected adults (AUC, 3,000 ng h/ml; Cmax, 300 ng/ml) treated with tenofovir DF at 300 mg. Highly active antiretroviral therapy (HAART) has altered the clinical course of human immunodeficiency virus (HIV) infection in children (6), but the virologic response rates of HAART are lower in children than in adults (12). The diminished efficacy of HAART in HIV-infected children and the need for simpler, more accessible antiretrovirals to prevent mother-to-child transmission (MTCT) of HIV present compelling reasons to develop new antiretroviral agents for use in infants and children. Separate clinical trials and pharmacological studies are conducted in the pediatric patient population to determine whether new agents pose any special risks for pediatric patients and whether drug metabolism is affected by the many developmental changes that occur during the newborn period, infancy, childhood, and adolescence (5). In previous studies of the nucleoside reverse transcriptase inhibitors and the nucleotide reverse transcriptase inhibitor adefovir, differences in absorption, metabolism, safety, and efficacy between pediatric patients and adults were demonstrated (1, 7–10). These age-related differences in drug disposition are most often reflected in an increased apparent clearance of the drug and/or lower bioavailability in children, necessitating higher doses per body weight or body surface area (BSA). Tenofovir disoproxil fumarate {tenofovir DF; formerly

This case series describes 4 children with vertically acquired human immunodeficiency virus (HIV) infection who exhibited immunologic, virologic, and clinical stability while on a protease inhibitor-containing highly active antiretroviral therapy (HAART) regimen, yet demonstrated significant cognitive decline as measured by standardized intelligence tests.A retrospective review of 107 patient records of children with HIV infection on HAART treatment protocols was conducted. Four patients were identified who responded to protease inhibitor-containing HAART therapy with sustained viral load suppression, and stable immunologic and medical parameters, yet demonstrated significant cognitive decline. Such discordance between biological and clinical markers previously has been reported in adults with HIV disease but not in children. This observed decline in neurocognitive functioning despite stable medical parameters suggests that HAART regimens that are effective for systemic disease may not be as effective for the central nervous system (CNS), perhaps because the antiretrovirals do not penetrate adequately into the CNS.Of note, 3 of these 4 patients did not have zidovudine (ZDV) included in their HAART regimen. The only patient who was treated with ZDV containing regimen received 90 mg/m2 every 6 hours, which is at the lower end of the recommended ZDV pediatric full-dose range (90 mg/m2 to 120 mg/m2). Two of the 4 patients began ZDV at 120 mg/m2 every 6 hours following the decline in their cognitive test scores and subsequently showed improved or stable functioning as evidenced by the results of follow-up psychometric testing.Long-term prospective studies using both systemic and CNS measures are necessary to further investigate the effects of HAART in children with HIV disease. Longitudinal cognitive assessments of children receiving HAART appear indicated to identify cognitive decline and to provide appropriate therapeutic intervention when manifestations of HIV-related CNS disease progression occur.

HHV-8 CELLULAR IMMUNE RESPONSES IN HOMOSEXUAL MEN: ABSTRACT 5 Howard Strickler;James Goedert;F. Bethke;C. Trubey;Thomas O'Brien;Joel Palefsky;James Whitman;Dharam Ablashi;Steven Zeichner;Gene Shearer; JAIDS Journal of Acquired Immune Deficiency Syndromes

Viral Kinetics after Initiation of Therapy are Predictive of Long-Term Response in HIV-Infected Children ♦ 882

Fetal and neonatal infections can occur at different times during pregnancy, from conception to birth. Infections that take place near the time of conception often destroy the zygote or embryo and only rarely leave definitive evidence. The mother can transmit the infection to her fetus through several routes, but the most likely routes are through ascending infections and through the blood. The inability of most agents to infect the early embryo probably depends largely on local barriers to the infectious agent, such as the zona pellucida. Some viruses, however, because of their systems for gene regulation of expression, can infect only embryos of certain developmental stages. Certain retroviruses can infect embryos, integrate into cellular DNA, and become part of the germline. After implantation, most infectious agents reach the fetus hematogenously. Organisms circulating in the mother reach and infect the placenta. They then may breach the placenta, gain access to the fetal circulation, and disseminate through the fetal body. Agents with particular tropisms infect particular organs and cause particular symptom complexes. The damage done by the organisms depends largely on the gestational age of the fetus at the time of the infection. The ability of the agent to infect or damage the fetus at all often depends on whether the mother is experiencing a primary infection or has previously mounted an effective immune response. Agents harm the fetus through direct destruction of parenchymal cells, through destruction of blood vessels and resulting infarction, through continued replication in fetal and neonatal tissues, through altering the growth parameters of various fetal tissues, and through provoking autoimmune responses. Infections that begin in the perinatal period usually infect the fetus by direct inoculation from infected foci in the birth canal or through direct contact with large amounts of infected maternal body fluids. Direct tissue destruction of the immediate sequelae of invasive infections usually causes the fetal damage from these perinatally acquired agents. The clinical features of the disease that begin in this period provide an opportunity for effective therapeutic intervention. Understanding the routes of fetal infection and the mechanisms underlying fetal damage from infection will help in devising strategies for preventing and treating congenital infections.