A Digital Platform to Support HIV Case Management for Youth and Young Adults: Mixed Methods Feasibility Study.

Background: Advances in medical treatments in recent years have contributed to an overall decline in HIV-related opportunistic infections and deaths in youth; however, mortality and morbidity rates in perinatally and nonperinatally infected adolescents and young adults (AYA) living with HIV remain relatively high today.

Objective: The goal of this project was to assess the use, utility, and cost-effectiveness of PlusCare, a digital app for HIV case management in AYA living with HIV. The app supports routine case management tasks, such as scheduling follow-up visits, sharing documents for review and signature, laboratory test results, and between-visit communications (eg, encouraging messages).

Presentation and outcomes of post-transplant lymphoproliferative disorder at a single institution pediatric transplant center.

Background: This study aimed to characterize features present at the time of diagnosis and describe outcomes in patients with post-transplant lymphoproliferative disorder (PTLD) following pediatric solid organ transplantation.

Methods: We performed a retrospective review of solid organ transplant patients who developed pathologically confirmed PTLD at our center from 2006 to 2016.

Results: Of 594 patients included in this study, 41(6.

Immune imbalance and activation are associated with lower lung function in youth with perinatally acquired HIV.

High CD8 T-cells and low CD4/CD8 are associated with lower lung function among youth living with perinatally-acquired HIV, despite antiretroviral therapy and CD4 preservation/reconstitution. Understanding these underlying mechanisms is critical to mitigate lung function impairment.

Birth Weight and Preterm Delivery Outcomes of Perinatally vs Nonperinatally Human Immunodeficiency Virus-Infected Pregnant Women in the United States: Results From the PHACS SMARTT Study and IMPAACT P1025 Protocol.

Background: Pregnancy outcomes of perinatally human immunodeficiency virus-infected women (PHIV) are poorly defined.

Methods: We compared preterm delivery and birth weight (BW) outcomes (low BW [LBW], <2500 g), small-for-gestational-age [SGA], and BW z scores [BWZ]) in HIV-exposed uninfected infants of PHIV vs nonperinatally HIV-infected (NPHIV) pregnant women in the Pediatric HIV/AIDS Cohort Study Surveillance Monitoring of ART Toxicities or International Maternal Pediatric Adolescent AIDS Clinical Trials P1025 studies. Mixed effects models and log binomial models were used to assess the association of maternal PHIV status with infant outcomes.

Association of Risk of Viremia, Immunosuppression, Serious Clinical Events, and Mortality With Increasing Age in Perinatally Human Immunodeficiency Virus-Infected Youth.

Importance: As perinatally human immunodeficiency virus-infected youth (PHIVY) in the United States grow older and more treatment experienced, clinicians need updated information about the association of age, CD4 cell count, viral load (VL), and antiretroviral (ARV) drug use with risk of opportunistic infections, key clinical events, and mortality to understand patient risks and improve care.

Objective: To examine the incidence or first occurrence during follow-up of key clinical events (including Centers for Disease Control and Prevention stage B [CDC-B] and stage C [CDC-C] events) and mortality among PHIVY stratified by age, CD4 cell count, and VL and ARV status.

Design, Setting, And Participants: Combining data from the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol and International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1074 multicenter cohort studies (March 2007 through April 2015), we estimated event rates during person-time spent in key strata of age (7-12, 13-17, and 18-30 years), CD4 cell count (<200, 200-499, and ≥500/μL), and a combined measure of VL and ARV status (VL <400 or ≥400 copies/mL; ARV therapy or no ARV therapy).

Lymphocyte subsets in HIV-exposed uninfected infants and HIV-unexposed uninfected infants.

HEU infants had higher CD19 B cell counts and % than HUU infants after the first 3 months of life, suggesting a B cell immune response with intrauterine exposure to maternal HIV or other pathogens.

Case Report of a Child after Hematopoietic Cell Transplantation with Acute Tracheobronchitis as a Cause for Respiratory Failure.

Rapid respiratory failure due to invasive mycosis of the airways is an uncommon presentation of infection, even in immunocompromised patients, and very few pediatric cases have been reported. Patients with tracheobronchitis present with nonspecific symptoms, and radiologic studies are often noninformative, leading to a delay in diagnosis. Prompt initiation of adequate antifungal therapies is of utmost importance to improve outcome.

Phenotypic Coreceptor Tropism in Perinatally HIV-infected Youth Failing Antiretroviral Therapy.

Background: Perinatally HIV-infected (PHIV) children and youth are often heavily treatment-experienced, with resultant antiretroviral resistance and limited treatment options. For those with virologic failure (VF), new agents such as CCR5 (R5) antagonists may be useful; however, reports of R5 antagonist susceptibility in children have mostly relied on genotypic testing, which may not accurately reflect the phenotypic tropism of the viral populations. We characterized phenotypic coreceptor usage among PHIV children and youth with VF on antiretroviral treatment to identify predictors of CXCR4 (X4) tropism which preclude R5 antagonist use.

Pharmacokinetics of Rilpivirine in HIV-Infected Pregnant Women.

Background: Rilpivirine pharmacokinetics is defined by its absorption, distribution, metabolism, and excretion. Pregnancy can affect these factors by changes in cardiac output, protein binding, volume of distribution, and cytochrome P450 (CYP) 3A4 activity. Rilpivirine is metabolized by CYP3A4.

Prevalence and Persistence of Varicella Antibodies in Previously Immunized Children and Youth With Perinatal HIV-1 Infection.

Background: Two doses of live-attenuated varicella-zoster vaccine are recommended for human immunodeficiency virus 1 (HIV-1)-infected children with CD4% ≥ 15%. We determined the prevalence and persistence of antibody in immunized children with perinatal HIV (PHIV) and their association with number of vaccinations, combination antiretroviral therapy (cART), and HIV status.

Methods: The Adolescent Master Protocol is an observational study of children with PHIV and perinatally HIV-exposed but uninfected (PHEU) children conducted at 15 US sites.

Immunity to Measles, Mumps, and Rubella in US Children With Perinatal HIV Infection or Perinatal HIV Exposure Without Infection.

Background: Children with perinatal human immunodeficiency virus (HIV) infection (PHIV) may not be protected against measles, mumps, and rubella (MMR) because of impaired initial vaccine response or waning immunity. Our objectives were to estimate seroimmunity in PHIV-infected and perinatally HIV-exposed but uninfected (HEU) children and identify predictors of immunity in the PHIV cohort.

Methods: PHIV and HEU children were enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) at ages 7-15 years from 2007 to 2009.

Pharmacokinetics of Once Versus Twice Daily Darunavir in Pregnant HIV-Infected Women.

Objective: To describe darunavir (DRV) pharmacokinetics with once-and twice-daily dosing during pregnancy and postpartum in HIV-infected women.

Design: Women were enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials Network Protocol P1026s, a prospective nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included separate cohorts receiving DRV/ritonavir dosed at either 800 mg/100 mg once daily or 600 mg/100 mg twice daily.

Methods: Intensive steady-state 12- or 24-hour pharmacokinetic profiles were performed during the second trimester, third trimester, and postpartum.

Raltegravir pharmacokinetics during pregnancy.

Objective: We evaluated the pharmacokinetics (PK) of raltegravir in HIV-infected women during pregnancy and postpartum.

Methods: International Maternal Pediatric Adolescent AIDS Clinical Trials 1026s is an ongoing prospective study of antiretroviral PK during pregnancy (NCT00042289). Women receiving 400 mg raltegravir twice daily in combination antiretroviral therapy had intensive steady-state 12-hour PK profiles performed during pregnancy and at 6- to 12-week postpartum.

Immunogenicity and tolerability to human papillomavirus-like particle vaccine in girls and young women with inflammatory bowel disease.

Background: Female patients receiving immunosuppressive therapy may be at increased risk for human papillomavirus (HPV) infection and cervical neoplasia.

Methods: We administered the 3-dose HPV vaccine Gardasil to 37 females aged 9 to 26 years with inflammatory bowel disease (IBD) prescribed immunosuppressive therapy (prospective cohort). Geometric mean titers (GMT) in milli-Merck (mMu/mL) units were determined before dose 1 and 1 month after dose 3 by competitive Luminex immunoassay (cLIA) and qualitatively compared with healthy females of similar age from Merck's database.

Pharmacokinetics of an increased atazanavir dose with and without tenofovir during the third trimester of pregnancy.

Background: Reduced atazanavir exposure has been demonstrated during pregnancy with standard atazanavir/ritonavir dosing. We studied an increased dose during the third trimester of pregnancy.

Methods: International Maternal Pediatric Adolescent AIDS Clinical Trials Group 1026s is a prospective, nonblinded, pharmacokinetic study of HIV-infected pregnant women taking antiretrovirals for clinical indications, including 2 cohorts (with or without tenofovir) receiving atazanavir/ritonavir 300/100 mg once daily during the second trimester, 400/100 mg during the third trimester, and 300/100 mg postpartum (PP).

The impact of RSV, adenovirus, influenza, and parainfluenza infection in pediatric patients receiving stem cell transplant, solid organ transplant, or cancer chemotherapy.

RVIs are a significant cause of morbidity and mortality in immunocompromised children. We analyzed the characteristics and outcomes of infection by four respiratory viruses (RSV, adenovirus, influenza, and parainfluenza) treated at a pediatric tertiary care hospital in a retrospective cohort of patients who had received cancer chemotherapy, hematopoietic stem cell, or SOT. A total of 208 infections were studied among 166 unique patients over a time period of 1993-2006 for transplant recipients, and 2000-2005 for patients with cancer.

T-cell activation and neurodevelopmental outcomes in perinatally HIV-infected children.

Objective: To evaluate baseline T-cell activation and neurodevelopmental outcomes over time in a cohort of perinatally HIV-infected (PHIV-infected) children with severe disease.

Design: Pediatric AIDS Clinical Trials Group protocol 366 (PACTG 366) was a partially randomized, open-label, multicenter 96-week antiretroviral treatment-algorithm study. Neurodevelopmental status, measured by age-dependent evaluations (Bayley scales of infant development-II; Wechsler preschool and primary scale of intelligence-revised; Wechsler intelligence scale for children-III), was a secondary outcome.

Maternal cytomegalovirus-specific immune responses and symptomatic postnatal cytomegalovirus transmission in very low-birth-weight preterm infants.

Introduction: Transmission of cytomegalovirus (CMV) via breast milk can lead to severe acute illness in very low-birth-weight (VLBW) preterm infants. Although the majority of CMV-seropositive women shed CMV in milk, symptomatic postnatal infection of VLBW infants occurs infrequently, suggesting that virologic or immunologic factors in milk may be associated with the risk and severity of postnatal CMV infection.

Methods: We investigated the magnitude of CMV-specific cellular and humoral immune responses in milk of 30 seropositive mothers of VLWB preterm infants and assessed their relationship to milk CMV load and symptomatic CMV transmission.

Wide prevalence of heterosubtypic broadly neutralizing human anti-influenza A antibodies.

Background: Lack of life-long immunity against influenza viruses represents a major global health care problem with profound medical and economic consequences. A greater understanding of the broad-spectrum "heterosubtypic" neutralizing human antibody (BnAb) response to influenza should bring us closer toward a universal influenza vaccine.

Methods: Serum samples obtained from 77 volunteers in an H5N1 vaccine study were analyzed for cross-reactive antibodies (Abs) against both subtype hemagglutinins (HAs) and a highly conserved pocket on the HA stem of Group 1 viruses.

CD4+ lymphocyte-based immunologic outcomes of perinatally HIV-infected children during antiretroviral therapy interruption.

Objective: To assess the characteristics and outcomes of antiretroviral treatment (ART) interruption (TI) in perinatally HIV-infected children.

Design: The Adolescent Master Protocol (AMP) of the Pediatric HIV/AIDS Cohort Study is a prospective cohort study that enrolled 7- to 16-year-old perinatally HIV-infected children between 2007 and 2009 from 15 sites in the United States and Puerto Rico.

Methods: TI was defined as ART discontinuation for ≥ 3 months after ≥ 6 months of continuous ART.

Antiretroviral treatment of US children with perinatally acquired HIV infection: temporal changes in therapy between 1991 and 2009 and predictors of immunologic and virologic outcomes.

Background: Advances in therapy have allowed children with perinatal HIV infection in the United States to survive into adolescence. We sought to describe the disease status of a large cohort of such children and identify predictors of their current CD4 count and HIV viral load (VL).

Methods: The Pediatric HIV/AIDS Cohort Study AMP Protocol is an ongoing prospective study conducted at 15 sites in the United States.

Atazanavir pharmacokinetics with and without tenofovir during pregnancy.

Background: Few data are available describing atazanavir exposure during pregnancy, especially when used in combination with tenofovir, whose coadministration with atazanavir results in decreased atazanavir exposure.

Design: International Maternal Pediatric Adolescent AIDS Clinical Trials 1026 s is an ongoing, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included 2 cohorts receiving atazanavir/ritonavir 300 mg/100 mg once daily, either with or without tenofovir.

Methods: Intensive steady-state 24-hour pharmacokinetic profiles were performed during the third trimester and at 6-12 weeks postpartum.

Lopinavir tablet pharmacokinetics with an increased dose during pregnancy.

Objective: Reduced lopinavir concentrations have been demonstrated with use of the capsule formulation during the third trimester of pregnancy. This study determined lopinavir exposure with an increased dose of the new tablet formulation during the third trimester.

Design: International Maternal Pediatric Adolescent AIDS Clinical Trials 1026s is a prospective nonblinded pharmacokinetic study in HIV-infected pregnant women, including a cohort receiving 2 lopinavir/ritonavir tablets (400 mg/100 mg) twice daily during the second trimester, 3 tablets (600 mg/150 mg) twice daily during the third trimester, and 2 tablets (400 mg/100 mg) twice daily post delivery through 2 weeks postpartum.