Primary isoniazid prophylaxis against tuberculosis in HIV-exposed children.

BACKGROUND: The dual epidemic of human immunodeficiency virus (HIV) and tuberculosis is a major cause of sickness and death in sub-Saharan Africa. We conducted a double-blind, randomized, placebo-controlled trial of preexposure isoniazid prophylaxis against tuberculosis in HIV-infected children and uninfected children exposed to HIV during the perinatal period. METHODS: We randomly assigned 548 HIV-infected and 804 HIV-uninfected infants (91 to 120 days of age) to isoniazid (10 to 20 mg per kilogram of body weight per day) or matching placebo for 96 weeks. All patients received bacille Calmette-Guérin (BCG) vaccination against tuberculosis within 30 days after birth. HIV-infected children had access to antiretroviral therapy. The primary outcome measures were tuberculosis disease and death in HIV-infected children and latent tuberculosis infection, tuberculosis disease, and death in HIV-uninfected children within 96 to 108 weeks after randomization. RESULTS: Antiretroviral therapy was initiated in 98.9% of HIV-infected children during the study. Among HIV-infected children, protocol-defined tuberculosis or death occurred in 52 children (19.0%) in the isoniazid group and 53 (19.3%) in the placebo group (P=0.93). Among HIV-uninfected children, there was no significant difference in the combined incidence of tuberculosis infection, tuberculosis disease, or death between the isoniazid group (39 children, 10%) and the placebo group (45 children, 11%; P=0.44). The rate of tuberculosis was 121 cases per 1000 child-years (95% confidence interval [CI], 95 to 153) among HIV-infected children as compared with 41 per 1000 child-years (95% CI, 31 to 52) among HIV-uninfected children. There were no significant differences in clinical or severe laboratory toxic effects between treatment groups. CONCLUSIONS: Primary isoniazid prophylaxis did not improve tuberculosis-disease-free survival among HIV-infected children or tuberculosis-infection-free survival among HIV-uninfected children immunized with BCG vaccine. Despite access to antiretroviral therapy, the burden of tuberculosis remained high among HIV-infected children. (Funded by the National Institutes of Health and Secure the Future; ClinicalTrials.gov number, NCT00080119.).

The association between the ratio of monocytes:lymphocytes at age 3 months and risk of tuberculosis (TB) in the first two years of life.

BACKGROUND: Recent transcriptomic studies revived a hypothesis suggested by historical studies in rabbits that the ratio of peripheral blood monocytes to lymphocytes (ML) is associated with risk of tuberculosis (TB) disease. Recent data confirmed the hypothesis in cattle and in adults infected with HIV. METHODS: We tested this hypothesis in 1,336 infants (540 HIV-infected, 796 HIV-exposed, uninfected (HEU)) prospectively followed in a randomized controlled trial of isoniazid prophylaxis in Southern Africa, the IMPAACT P1041 study. We modeled the relationship between ML ratio at enrollment (91 to 120 days after birth) and TB disease or death in HIV-infected children and latent Mycobacterium tuberculosis (MTB) infection, TB disease or death in HEU children within 96 weeks (with 12 week window) of randomization. Infants were followed-up prospectively and routinely assessed for MTB exposure and outcomes. Cox proportional hazards models allowing for non-linear associations were used; in all cases linear models were the most parsimonious. RESULTS: Increasing ML ratio at baseline was significantly associated with TB disease/death within two years (adjusted hazard ratio (HR) 1.17 per unit increase in ML ratio; 95% confidence interval (CI) 1.01 to 1.34; P = 0.03). Neither monocyte count nor lymphocyte counts alone were associated with TB disease. The association was not statistically dissimilar between HIV infected and HEU children. Baseline ML ratio was associated with composite endpoints of TB disease and death and/or TB infection. It was strongest when restricted to probable and definite TB disease (HR 1.50; 95% CI 1.19 to 1.89; P = 0.006). Therefore, per 0.1 unit increase in the ML ratio at three to four months of age, the hazard of probable or definite TB disease before two years was increased by roughly 4% (95% CI 1.7% to 6.6%). CONCLUSION: Elevated ML ratio at three- to four-months old is associated with increased hazards of TB disease before two years among children in Southern Africa. While significant, the modest effect size suggests that the ML ratio plays a modest role in predicting TB disease-free survival; its utility may, therefore, be limited to combination with existing tools to stratify TB risk, or to inform underlying pathophysiologic determinants of TB disease.

Isoniazid pharmacokinetics, pharmacodynamics, and dosing in South African infants.

AIMS: There are limited data on isoniazid (INH) pharmacokinetics in infants and young children and, therefore, uncertainty on appropriate dosing. METHODS: Pharmacokinetic data were obtained from perinatally HIV-exposed South African infants aged 3-24 months receiving INH 10-20 mg·kg·d orally for Mycobacterium tuberculosis prophylaxis. INH pharmacokinetic parameters were characterized using a population pharmacokinetic approach. Dosing simulations were performed to evaluate weight-based INH doses in children based on N-acetyltransferase 2 enzyme (NAT2) genotype, age, maximum concentrations (Cmax) ≥3 mg/L, and area under the curve (AUC0-24) ≥10.52 mg·h/L. RESULTS: In 151 infants (53% female, 48% HIV positive) receiving a mean INH dose of 14.5 mg·kg·d, mean (±SD) Cmax at 3, 6, and 23 months of age were 10.0 (3.5), 8.6 (2.6), and 9.3 (3.8) mg/L, respectively, mean (±SD) AUC0-24 were 53.6 (26.8), 42 (19.9), and 44 (30.7) mg·h/L, respectively, and mean (±SD) half-lives were 2.1 (0.7), 1.9 (0.6), and 1.8 (0.9) hours, respectively. A trimodal apparent oral clearance of INH as a function of the NAT2 genotype was apparent as early as 3 months. INH was well tolerated. At an average INH dose of 14.5 mg·kg·d, 99% of infants aged 3-24 months have an INH Cmax ≥3 mg/L, and 98% have an INH AUC0-24 ≥10.52 mg·h/L. CONCLUSIONS: INH at an average dose of 14.5 mg/kg once daily was well tolerated in infants and achieved INH Cmax values ≥3 mg/L and AUC0-24 values ≥10.52 mg·h/L.

Anti-NMDAR Encephalitis After Neonatal HSV-1 Infection in a Child With Low TLR-3 Function.

Neonatal herpes simplex virus encephalitis (HSVE) often results in long-lasting neuro-disability in affected children. In addition to primary HSVE and HSVE relapses, children with herpes simplex virus are at increased risk of developing anti-N-methyl-d-aspartate receptor encephalitis (NMDARe), an autoimmune encephalitis. In this study, we describe a patient with neonatal disseminated herpes infection, who developed HSVE after discontinuation of 2 years of acyclovir suppressive therapy. After resolution of HSVE, the patient rapidly deteriorated with significant behavioral and neurologic changes including emotional outbursts, fearfulness, involuntary movements, and focal seizures. The patient was diagnosed with anti-NMDARe and was later found to have low toll-like receptor-3 function. In this study, we review published pediatric cases of anti-NMDARe after HSVE as well as previous literature and primary data examining the presentation, predisposing risk factors, predictive outcomes, future directions, and the role of immunodeficiency in HSVE-mediated anti-NMDARe. The neonatal immune system and developing brain are disproportionately vulnerable to early viral exposure; therefore, it is important to recognize the value of early immunodeficiency screening in patients with neonatal herpes simplex virus. By understanding the immune landscape within this patient population, we can mitigate long-term neurologic disability and improve the quality of life of affected children.

Long-term follow-up of post-cardiac surgery Mycobacterium chimaera infections: A 5-center case series.

OBJECTIVES: In multiple countries, endovascular/disseminated Mycobacterium chimaera infections have occurred in post-cardiac surgery patients in association with contaminated, widely-distributed cardiac bypass heater-cooler devices. To contribute to long-term characterization of this recently recognized infection, we describe the clinical course of 28 patients with 3-7 years of follow-up for survivors. METHODS: Identified at five hospitals in the United States 2010-2016, post-cardiac surgery patients in the cohort had growth of Mycobacterium avium complex (MAC)/M. chimaera from a sterile site or surgical wound, or a clinically compatible febrile illness with granulomatous inflammation on biopsy. Case follow-up was conducted in May 2019. RESULTS: Of 28 patients, infection appeared to be localized to the sternum in four patients. Among 18 with endovascular/disseminated infection who received combination anti-mycobacterial treatment and had sufficient follow-up, 39% appeared to have controlled infection (>12 months), 56% died, and one patient is alive with relapsed bacteremia. While the number of patients is small and interpretation is limited, four (67%) of six patients who had cardiac prosthesis removal/replacement appeared to have controlled infection compared to three (25%) of 12 with retained cardiac prosthesis (p >0.14; Fisher's exact test). CONCLUSIONS: Given poor response to treatment and potential for delayed relapses, post-cardiac surgery M. chimaera infection warrants aggressive treatment and long-term monitoring.

Management of newborns exposed to mothers with confirmed or suspected COVID-19.

There is limited information about newborns with confirmed or suspected COVID-19. Particularly in the hospital after delivery, clinicians have refined practices in order to prevent secondary infection. While guidance from international associations is continuously being updated, all facets of care of neonates born to women with confirmed or suspected COVID-19 are center-specific, given local customs, building infrastructure constraints, and availability of protective equipment. Based on anecdotal reports from institutions in the epicenter of the COVID-19 pandemic close to our hospital, together with our limited experience, in anticipation of increasing numbers of exposed newborns, we have developed a triage algorithm at the Penn State Hospital at Milton S. Hershey Medical Center that may be useful for other centers anticipating a similar surge. We discuss several care practices that have changed in the COVID-19 era including the use of antenatal steroids, delayed cord clamping (DCC), mother-newborn separation, and breastfeeding. Moreover, this paper provides comprehensive guidance on the most suitable respiratory support for newborns during the COVID-19 pandemic. We also present detailed recommendations about the discharge process and beyond, including providing scales and home phototherapy to families, parental teaching via telehealth and in-person education at the doors of the hospital, and telehealth newborn follow-up.

Customizing an Electronic Medical Record to Automate the Workflow and Tracking of an Antimicrobial Stewardship Program.

BACKGROUND: Documenting the actions and effects of an antimicrobial stewardship program (ASP) is essential for quality improvement and support by hospital leadership. Thus, our ASP tallies the number of charts reviewed, types of recommendations, how and to whom they were communicated, whether they were followed, and any effects on antimicrobial days of therapy. Here we describe how we customized the electronic medical record at our institution to facilitate our workflow and data analysis, while highlighting principles that should be adaptable to other ASPs. METHODS: The documentation system involves creation of a novel and intuitive ASP form in each chart reviewed and 2 mutually exclusive tracking systems: 1 for active forms to facilitate the daily ASP workflow and 1 for finalized forms to generate cumulative reports. The ASP form is created by the ASP pharmacist, edited by the ASP physician, reopened by the pharmacist to assess whether the recommendation was followed and to quantify any antimicrobial days avoided or added, then reviewed and finalized by the ASP physician. Active forms are visible on a real-time "MPage," whereas all finalized forms are compiled nightly into 65 informative tables and associated graphs. RESULTS AND CONCLUSIONS: This system and its underlying principles have automated much of the documentation, facilitated follow-up of interventions, improved the completeness and validity of recorded data and analysis, enabled our ASP to expand its activities, and been associated with decreased antimicrobial usage, drug resistance, and C. difficile infections.

Pediatric tuberculosis consultations across 5 CDC regional tuberculosis training and medical consultation Centers.

BACKGROUND: The U.S. Centers for Disease Control and Prevention (CDC) funds five Regional Tuberculosis Training and Medical Consultation Centers (RTMCCs) that provide training and consultation for tuberculosis (TB) control and management. RTMCC utilization for assistance with diagnosis and management of TB in children has not been described. We analyzed pediatric TB consultations performed across all RTMCCs in terms of question type, provider type, and setting. METHODS: The CDC medical consultation database was queried for consultations regarding patients ≤ 18 years provided between 1/1/13-4/22/15 by all RTMCCs (Curry International TB Center, Heartland National TB Center, Mayo Clinic Center for TB, New Jersey Medical School Global TB Institute, Southeastern National TB Center). Each query was categorized into multiple subject areas based on provider type, setting, consultation topic, and patient age. RESULTS: The 5 RTMCCs received 1164 pediatric consultation requests, representing approximately 20% of all consultations performed by the centers during the study period. Providers requesting consults were primarily physicians (46.3%) or nurses (45.0%). The majority of pediatric consult requests were from state and local public health departments (679, 58.3%) followed by hospital providers (199, 17.1%); fewer requests came from clinicians in private practice (84, 7.2%) or academic institutions (40, 3.4%). Consults addressed 14 different topics, most commonly management of children with TB disease (19.1%), latent TB infection (LTBI) (18.2%), diagnosis or laboratory testing (18.7%), and pharmacology (9.2%). DISCUSSION: Pediatric consultations accounted for approximately 20% of all consultations performed by RTMCCs during the study period. RTMCCs were utilized primarily by public health departments regarding management of TB disease, LTBI, and diagnosis or laboratory testing. The relative underutilization of the RTMCCs by clinicians in non-public health settings, who often manage children with TB exposure or infection, warrants further study. As US TB case rates decline and providers become less experienced with childhood TB, medical consultation support may become increasingly important.

High Incidence of Tuberculosis Infection in HIV-exposed Children Exiting an Isoniazid Preventive Therapy Trial.

Young HIV-exposed children are at high risk for TB infection. We performed QuantiFERON-TB Gold among HIV-exposed children in South Africa at enrolment and 1-year follow-up. The incidence of TB infection was high for HIV+ (11 cases per 100 child-years) and HIV-exposed uninfected children (15 cases per 100 child-years). QuantiFERON-TB Gold may identify HIV-exposed children at risk for TB disease progression.

Malignancy in perinatally human immunodeficiency virus-infected children in the United States.

OBJECTIVES: To determine the incidence of and factors associated with malignancy in perinatally human immunodeficiency virus (HIV)-infected children in the United States. METHODS: Included were 2969 children followed in the Pediatric AIDS Clinical Trials Group (PACTG) 219/219C cohort from 1993 through 2003. Cancer incidence by sex, race, age, histology and highly active antiretroviral therapy (HAART) era (pre-HAART, 1993-1997; HAART, 1998-2003) was estimated, and the standardized incidence ratio contrasting infected and uninfected children was determined. Poisson regression was used to further investigate the relation between HAART use (> or =3 drugs of > or =2 classes, 1 of which was a protease inhibitor), CD4% and cancer. RESULTS: There were 37 cancers (17 prevalent and 20 incident) diagnosed in 2969 children for a prevalence of 0.6% [95% confidence interval (CI), 0.3, 0.9] and an incidence of 1.56/1000 person-years (95% CI 0.95, 2.41). Compared with uninfected children, the standardized incidence ratio was 10.08 (95% CI 5.87, 16.14). Incidence did not significantly differ by sex, race, age or HAART era. Of the cases, 35% were immunocompetent (CD4 > or =25%), 25% were moderately immunosuppressed (15%< or = CD4 < or =24%) and 40% were severely immunosuppressed (CD4 <15%) at diagnosis. In multivariate regression, the cancer rate was 3.09 (95% CI 1.22, 7.85) times higher in children with < or =2 years of HAART use than in children with >2 years of HAART and 3.20 (95% CI 1.32, 7.76) times higher in children with CD4 <15% at cohort enrollment than in children with CD4 > or =15%. CONCLUSION: Cancer incidence in this U.S. pediatric cohort was lower than that of European cohorts but was markedly higher than that of HIV-uninfected children. Cancer incidence was highest in children who were severely immunosuppressed and in children who received HAART for < or =2 years.

Protracted symptoms in lymphocytic choriomeningitis: a case report.

Assumed to be underreported and underrecognized, lymphocytic choriomeningitis presents as a febrile illness transmitted by the common house mouse, Mus musculus. Although asymptomatic or mild febrile illnesses are commonplace, meningitis and meningoencephalitis may develop after symptoms have seemed to improve. Neurologic sequelae are not typical but have been reported and can persist for months. We report a documented case of lymphocytic choriomeningitis in which a previously healthy 17-year-old girl experienced debilitating recurrent headaches and arthralgias for more than a year after discharge. Neuropsychological testing and visual changes were also documented. Further research is needed to estimate the prevalence of this infection, although it has been estimated that 5% of American adults have antibodies to lymphocytic choriomeningitis virus. Education and awareness of the medical community as well as the general public will be critical in prevention as well as advancing future treatment modalities of lymphocytic choriomeningitis virus.

Persistent non-gastrointestinal metabolic acidosis in pediatric HIV-1 infection.

OBJECTIVES: To determine the incidence and to identify the clinical parameters associated with non-gastrointestinal renal tubular and high anion gap acidosis in a cohort of HIV-1-infected children. METHODS: Records of 202 HIV-1-infected children were reviewed to identify patients with metabolic acidosis. Serum and urine chemistries of those children with persistent non-gastrointestinal acidosis were then studied prospectively. Serum and urinary anion gaps (SAG and UAG) were calculated. Those with acidosis (group 1) were compared with children without acidosis (group 2). Associations were determined with Pediatric HIV classification, height, weight, antiretroviral therapy, and Pneumocystis carinii pneumonia prophylaxis. RESULTS: Persistent acidosis was noted in 34 out of 202 children (17%): 16 out of 34 (47%, group 1A) had elevated SAG acidosis, and 18 out of 34 (53%) had normal SAG acidosis with a positive UAG (distal renal tubular) acidosis (group 1B). Those with acidifying defects more often received P. carinii pneumonia prophylaxis (P = 0.02 and 0.01 for groups 1 and 1A, respectively) independently of HIV-1 classification. This group was shorter in height than group 2 (P = 0.007). Differences in weight were not significant (P = 0.1). However, acidotic subjects were more immunocompromised than those in group 2 (multivariate P < 0.001 for HIV classification C3). CONCLUSIONS: Elevated SAG acidosis and renal tubular acidosis are not uncommon among HIV-infected children with advanced disease. These disorders may be associated with height growth failure and prophylaxis with sulfur/sulfone containing antibiotics. HIV infection and/or its associated therapies may cause renal tubular damage. The causes of elevated SAG acidosis require further investigation.

Testing for meningitis in children with bronchiolitis.

Viral bronchiolitis accounts for almost 20% of all-cause hospitalizations of infants (ie, children younger than age 1 year). The annual incidence of fever in viral bronchiolitis has been documented at 23% to 31%. However the incidence of concurrent serious bacterial infections is low (1%-7%), with meningitis occurring in less than 1% to 2% of cases, but lumbar puncture is performed in up to 9% of viral bronchiolitis cases. To our knowledge, no study has examined clinical factors that influence a physician's decision to perform a lumbar puncture in the setting of viral bronchiolitis. We present a retrospective, case-control study of hospitalized infants younger than one year diagnosed with viral bronchiolitis who underwent lumbar puncture as part of an evaluation for meningitis. The objective of the study was to determine clinical factors that influence a physician's decision to perform a lumbar puncture in the setting of viral bronchiolitis. Although the presence of apnea, cyanosis, meningeal signs, positive urine culture results, and young age were factors found to be preliminarily associated with the performance of a lumbar puncture in the setting of bronchiolitis, young age was the only significant clinical factor found after multivariable regression; no other demographic, clinical, laboratory, or radiologic variables were found to be significant.

Clostridium septicum gas gangrene in a previously healthy 8-year-old female with survival.

We present the only reported case of an immunocompetent pediatric patient in the literature to have fulminate gas gangrene of the lower extremity and concomitant gastrointestinal tract infection due to Clostridium septicum coinfected with Clostridium difficile colitis respectively. The patient survived with aggressive medical and surgical treatment.

Residual NADPH oxidase activity and isolated lung involvement in x-linked chronic granulomatous disease.

Chronic granulomatous disease (CGD) is characterized by inherited immune defects resulting from mutations in the NADPH oxidase complex genes. The X-linked type of CGD is caused by defects in the CYBB gene that encodes gp91-phox, a fundamental component of the NADPH oxidase complex. This mutation originates the most common and severe form of CGD, which typically has absence of NADPH oxidase function and aggressive multisystemic infections. We present the case of a 9-year-old child with a rare CYBB mutation that preserves some NADPH oxidase activity, resulting in an atypical mild form of X-linked CGD with isolated lung involvement. Although the clinical picture and partially preserved oxidase function suggested an autosomal recessive form of CGD, genetic testing demonstrated a mutation in the exon 3 of CYBB gene (c.252 G>A, p.Ala84Ala), an uncommon X-linked CGD variant that affects splicing. Atypical presentation and diagnostic difficulties are discussed. This case highlights that the diagnosis of mild forms of X-linked CGD caused by rare CYBB mutations and partially preserved NADPH function should be considered early in the evaluation of atypical and recurrent lung infections.

Psychological factors, beliefs about medication, and adherence of youth with human immunodeficiency virus in a multisite directly observed therapy pilot study.

This study examined psychological functioning and beliefs about medicine in adolescents with human immunodeficiency virus (HIV) on highly active antiretroviral therapy in a community-based directly observed therapy (DOT) pilot feasibility study. Participants were youth with behaviorally acquired HIV (n = 20; 65% female; median age, 21 years) with adherence problems, who received once-daily DOT. Youth were assessed at baseline, week 12 (post-DOT), and week 24 (follow-up). At baseline, 55% of youth reported having clinical depressive symptoms compared to 27% at week 12 with sustained improvements at week 24. At baseline, substance use was reported within the borderline clinical range (T(score) = 68), with clinical but statistically nonsignificant improvement (T(score) = 61) at week 12. Hopelessness scores reflected optimism for the future. Coping strategies showed significantly decreased cognitive avoidance (p = .02), emotional discharge (p = .004), and acceptance/resignation ("nothing I can do," p = .004), whereas positive reappraisal and seeking support emerged. With the exception of depressive symptoms, week 12 improvements were not sustained at week 24. DOT adherence was predicted by higher baseline depression (p = .05), beliefs about medicine (p = .006) and perceived threat of illness scores (p = .03). Youth with behaviorally acquired HIV and adherence problems who participated in a community-based DOT intervention reported clinically improved depressive symptoms, and temporarily reduced substance use and negative coping strategies. Depressive symptoms, beliefs about medicine, and viewing HIV as a potential threat predicted better DOT adherence.

Directly observed therapy (DOT) for nonadherent HIV-infected youth: lessons learned, challenges ahead.

Adherence to medications is critical to optimizing HIV care and is a major challenge in youth. The utility of directly observed therapy (DOT) to improve adherence in youth with HIV remains undefined and prompted this pilot study. Four U.S. sites were selected for this 24-week cooperative group study to assess feasibility and to identify the logistics of providing DOT to HIV-infected youth with demonstrated adherence problems. Once-a-day DOT was provided by DOT facilitators at the participant's choice of a community-based location and DOT tapered over 12 weeks to self-administered therapy based on ongoing adherence assessments. Twenty participants, median age 21 years and median CD4 227 cells/microl, were enrolled. Participants chose their homes for 82% of DOT visits. Compliance with recommended DOT visits was (median) 91%, 91%, and 83% at weeks 4, 8, and 12, respectively. Six participants completed >90% of the study-specified DOT visits and successfully progressed to self-administered therapy (DOT success); only half sustained >90% medication adherence 12 weeks after discontinuing DOT. Participants considered DOT successes were more likely to have higher baseline depression scores (p = 0.046). Via exit surveys participants reported that meeting with the facilitator was easy, DOT increased their motivation to take medications, they felt sad when DOT ended, and 100% would recommend DOT to a friend. In conclusion, this study shows that while community-based DOT is safe, feasible, and as per participant feedback, acceptable to youth, DOT is not for all and the benefits appear short-lived. Depressed youth appear to be one subgroup that would benefit from this intervention. Study findings should help inform the design of larger community-based DOT intervention studies in youth.

Development of a directly observed therapy adherence intervention for adolescents with human immunodeficiency virus-1: application of focus group methodology to inform design, feasibility, and acceptability.

PURPOSE: To obtain input from adolescents with human immunodeficiency virus-1 (HIV-1) infection to inform the design of a community-based modified directly observed therapy (MDOT) antiretroviral adherence intervention. METHODS: Pediatric AIDS Clinical Trials Group (PACTG) protocol 1036A conducted three focus groups with 17 adolescents aged 17-22 years (10 female, 65% African-American) from three geographically distinct US PACTG sites. Focus group sessions were scripted, audio-taped, and transcribed verbatim. A coding dictionary was developed and validated; Ethnograph version 5.08 was used to summarize coded data across and within the three sites. Prevalent themes were identified via frequencies and are reported as percentages. RESULTS: Adolescents provided the following specific input: the MDOT provider should be familiar with the participant and empathic; the MDOT location should be mutually agreed on, flexible, and private; and participant and provider communication should be bidirectional, preferably by phone. Ideally the MDOT program should be continued until adolescents independently demonstrate adherence and should include a weaning phase as a test of skill acquisition. The most commonly endorsed barrier to the proposed program was that MDOT would be an invasion of privacy. Initially, after introduction to the purpose of the focus group, all but one adolescent expressed the belief that MDOT could benefit persons other than themselves; however, at the conclusion of the focus group discussion, a significant shift in openness to the intervention occurred, in that 11 participants indicated they would consider participation in an MDOT program if such a program were offered. CONCLUSIONS: Focus group feedback clarified the feasibility, logistics, and patient concerns about the design and implementation of a proposed MDOT intervention for adolescents with HIV-1 infection who struggle with medication adherence.

Adjunctive treatment of disseminated Mycobacterium avium complex infection with interferon alpha-2b in a patient with complete interferon-gamma receptor R1 deficiency.

We report adjunct treatment of (interferon) IFN-alpha2b (Intron-A) in a patient with complete interferon-gamma receptor R1 (IFNGR1) deficiency suffering from disseminated infection with Mycobacterium avium complex (MAC) resistant to multiple anti-mycobacterial agents. A low dose of IFN-alpha2b (3 x 10(6) units/m(2) three times weekly subcutaneously) successfully attenuated progressive hepatosplenomegaly and abdominal/retroperitoneal/pelvic lymphadenopathy, although the patient continued to be mycobacteremic. This is the first report of a complete IFNGR1 deficiency treated with adjuvant IFN-alpha2b for disseminated MAC infection.

Clinical response and tolerability to and safety of saquinavir with low-dose ritonavir in human immunodeficiency virus type 1-infected mothers and their infants.

Saquinavir boosted with low-dose ritonavir given with zidovudine and lamivudine was well tolerated by pregnant women and their infants. All mothers had <400 human immunodeficiency virus type 1 RNA copies/ml at delivery. Two had elevated liver transaminases and amylase. Seven infant adverse events were possibly treatment related (anemia, neutropenia, and hyperbilirubinemia).