Mixed Methods Evaluation of the Impact of the COVID-19 Pandemic on Immigrant Families.

Introduction: Little is known about the experiences of immigrant families with COVID-19 illness. This mixed methods study compared child and household experiences at the time of a child's COVID-19 diagnosis between immigrant and US-born parents and explored immigrant Latino perspectives on underlying causes of COVID-19 disparities between immigrant and US-born families. Methods: Study data includes surveys of parents of a child with a positive SARS-CoV2 test resulting at Children's Hospital Colorado and focus groups with Latino immigrant adults. We compared household COVID-19 experiences, use of mitigation measures, vaccine intention and sociodemographic information between survey participants stratified by nativity and completed thematic qualitative data analysis. Results: Findings from quantitative data were reinforced by qualitative data including: lower socio-economic status and higher employment in essential services increased infections and spread in immigrant families and higher risk of limited information access related to language barriers and prevalent misinformation. Survey results showed no difference in COVID-19 vaccine intention by nativity. Focus group participants reported limited access to non-English language culturally-tailored vaccine information and competing work demands decreased uptake. Conclusion: Avoiding exacerbating disparities in the face of another public health emergency requires focused investments in policies and approaches specifically directed at immigrant communities.

Modern antiretroviral regimens in pregnant women: virologic outcomes and durability.

OBJECTIVES: Data are lacking on the virologic efficacy and durability of modern antiretroviral treatment (ART) regimens during pregnancy. We compared virologic outcomes at delivery among women receiving dolutegravir versus other ART and the rate of change of the initial pregnancy regimen. DESIGN: Single-site retrospective cohort between 2009 and 2019. METHODS: We used univariable and multivariable generalized estimating equations to model the relationship between the maternal ART anchor and the proportion of women with a detectable viral load (greater than or equal to 20 HIV RNA copies/mL of plasma) closest to delivery (suboptimal virologic control) and with a detectable viral load at any time in the third trimester. We also compared changes in ART during pregnancy. RESULTS: We evaluated 230 pregnancies in 173 mothers. Rates of optimal virologic control at delivery did not significantly differ in mothers who received dolutegravir (93.1%), rilpivirine (92.1%), boosted darunavir (82.6%), or efavirenz (76.9%) but were significantly lower among mothers receiving atazanavir (49.0%) or lopinavir (40.9%). The odds of having a detectable viral load at any time in the third trimester was also higher for atazanavir and lopinavir. Raltegravir, elvitegravir, or bictegravir were used in less than 10 mothers at delivery, which precluded statistical analyses. The frequency of change in ART was significantly higher in mothers who initially received elvitegravir (68%) or efavirenz (47%) than dolutegravir (18%). CONCLUSION: Dolutegravir-containing, rilpivirine-containing, and boosted darunavir-containing regimens conferred excellent virologic control in pregnancy. Atazanavir and lopinavir, elvitegravir, and efavirenz were associated with either high rates of virologic failure or regimen change during pregnancy.

Variation over Time in Child and Neighborhood Characteristics Associated with COVID-19.

Introduction: To examine the associations between child and neighborhood characteristics and incidence of COVID-19 infection during the first 19 months of the pandemic. Study Design: We utilized individual electronic health record data and corresponding census tract characteristics for pediatric SARS-CoV-2 cases (age <18 years) from March 23, 2020 to September 30, 2021 with molecular tests resulted at a children's health system in Colorado. We compared associations between individual SARS-CoV-2 cases and census tract SARS-CoV-2 positivity rates over three time periods (TP1: March-September 2020; TP2: October 2020-March 2021; TP3: April-September 2021) using multinomial logistic regression for individual associations and negative binomial regression for census tract associations. Results: We included 7498 pediatric SARS-CoV-2 cases and data from 711 corresponding census tracts. Spanish preferred health care language was associated with SARS-CoV-2 positivity for TP1 (odds ratio [OR] 4.9, 95% confidence interval [CI] 3.7-6.5) and TP2 (OR 2.01, 95% CI 1.6-2.6) compared with TP3. Other non-English preferred health care language was associated with SARS-CoV-2 positivity in TP1 (OR 2.4, 95% CI 1.4-4.2). Increasing percentage internationally born in a census tract was associated with SARS-CoV-2 positivity for TP1 (multivariable incident rate ratio [IRR]=1.040, p<0.0001), TP2 (multivariable IRR=1.028, p<0.0001), and in all TP combined (multivariable IRR=1.024, p<0.0001). Discussion: Our study is notable for the identification of COVID-19 disparities among children in immigrant families and communities, particularly early in the pandemic. Addressing disparities for immigrant communities requires targeted investments in public health infrastructure.

Congenital malformations and preeclampsia associated with integrase inhibitor use in pregnancy: A single-center analysis.

BACKGROUND: Antiretroviral therapy (ART) decreases perinatal HIV transmission, but concerns exist regarding maternal and infant safety. We compared the incidence of congenital malformations and other adverse outcomes in pregnancies exposed to integrase inhibitor (INSTI) versus non-INSTI ART. SETTING: Single-site review of all pregnancies among women living with HIV between 2008 and 2018. METHODS: We used binomial family generalized estimating equations to model the relationship of congenital anomalies and pregnancy outcomes with exposure to INSTI or dolutegravir (DTG) versus non-INSTI ART. RESULTS: Among 257 pregnancies, 77 women received ≥1 INSTI (54 DTG, 14 elvitegravir, 15 raltegravir), 167 received non-INSTI, and 3 had missing data. Fifty congenital anomalies were identified in 36 infants. Infants with first-trimester DTG or any first-trimester INSTI exposure had higher odds of congenital anomalies than infants with first-trimester non-INSTI exposure (OR = 2.55; 95%CI = 1.07-6.10; OR = 2.61; 95%CI = 1.15-5.94, respectively). Infants with INSTI exposure after the second trimester had no increased odds of anomalies. Women with INSTI exposure had higher odds of preeclampsia (OR = 4.73; 95%CI = 1.70-13.19). Among women who received INSTI, grade ≥3 laboratory abnormalities were noted in 2.6% while receiving the INSTI and 3.9% while not receiving the INSTI, versus 16.2% in women who received non-INSTI. There was no association between INSTI exposure and other pregnancy outcomes. CONCLUSION: In our cohort, first-trimester INSTI exposure was associated with increased rates of congenital anomalies and use of INSTI during pregnancy was associated with preeclampsia. These findings underscore the need for continued monitoring of the safety of INSTI in pregnancy.

Development and Implementation of an Interdisciplinary Model for the Management of Breastfeeding in Women With HIV in the United States: Experience From the Children's Hospital Colorado Immunodeficiency Program.

BACKGROUND: Women with HIV in high-income settings have increasingly expressed a desire to breastfeed their infants. Although national guidelines now acknowledge this choice, detailed recommendations are not available. We describe the approach to managing care for breastfeeding women with HIV at a single large-volume site in the United States. METHODS: We convened an interdisciplinary group of providers to establish a protocol intended to minimize the risk of vertical transmission during breastfeeding. Programmatic experience and challenges are described. A retrospective chart review was conducted to report the characteristics of women who desired to or who did breastfeed between 2015 and 2022 and their infants. RESULTS: Our approach stresses the importance of early conversations about infant feeding, documentation of feeding decisions and management plans, and communication among the health care team. Mothers are encouraged to maintain excellent adherence to antiretroviral treatment, maintain an undetectable viral load, and breastfeed exclusively. Infants receive continuous single-drug antiretroviral prophylaxis until 4 weeks after cessation of breastfeeding. From 2015 to 2022, we counseled 21 women interested in breastfeeding, of whom 10 women breastfed 13 infants for a median of 62 days (range, 1-309). Challenges included mastitis (N = 3), need for supplementation (N = 4), maternal plasma viral load elevation of 50-70 copies/mL (N = 2), and difficulty weaning (N = 3). Six infants experienced at least 1 adverse event, most of which were attributed to antiretroviral prophylaxis. DISCUSSION: Many knowledge gaps remain in the management of breastfeeding among women with HIV in high-income settings, including approaches to infant prophylaxis. An interdisciplinary approach to minimizing risk is needed.

Changing Characteristics of Children With COVID-19 in Colorado Admitted During Different Variant Periods.

BACKGROUND: Data are lacking on the impact of different severe acute respiratory syndrome coronavirus 2 variants in children and on pediatric vaccine effectiveness. We examined differences among children requiring hospital admission associated with coronavirus disease 2019 (COVID-19) during wild type, Delta and Omicron variant periods and calculated vaccine effectiveness at preventing symptomatic hospitalization during the Delta and Omicron variant periods. METHODS: We conducted a retrospective review of children younger than 21 years of age hospitalized with symptomatic COVID-19. Characteristics were compared between variant periods using Kruskal-Wallis or generalized Fisher exact tests. We estimated vaccine effectiveness in preventing symptomatic hospitalization. RESULTS: We included 115 children admitted during the wild type period, 194 during Delta and 226 during the Omicron periods. Median age (years) decreased (12.2 wild type, 5.9 Delta, 1.3 Omicron periods, P < 0.0001) over time. Children were less likely to have a comorbid condition, including diabetes or obesity, and had shorter admissions during Omicron compared with the wild type and Delta periods. Intensive care unit admissions and respiratory support requirements were highest during the Delta period ( P = 0.05). Among children ≥12 years, adjusted vaccine effectiveness at preventing symptomatic hospitalization was 86% during Delta and 45% during Omicron periods. CONCLUSIONS: Children hospitalized with COVID-19 during later variant periods were younger and less likely to have comorbidities. Children admitted during the Delta variant period required more intensive care and respiratory support compared to other variant periods. Vaccination was less effective at preventing symptomatic hospital admission during the Omicron period compared to the Delta period.

Impaired functionality of antigen presenting cells in HIV- exposed uninfected infants in the first six months of life.

HIV-exposed uninfected infants (HEU) have increased morbidity and mortality due to infections in the first 6 months of life that tapers down to 2 years of life. The underlying immunologic defects remain undefined. We investigated antigen-presenting cells (APC) by comparing the phenotype of unstimulated APC, responses to toll-like receptor (TLR) stimulation, and ability to activate natural killer (NK) cells in 24 HEU and 64 HIV-unexposed infants (HUU) at 1-2 days of life (birth) and 28 HEU and 45 HUU at 6 months of life. At birth, unstimulated APC showed higher levels of activation and cytokine production in HEU than HUU and stimulation with TLR agonists revealed lower expression of inflammatory cytokines and activation markers, but similar expression of IL10 regulatory cytokine, in APC from HEU compared to HUU. Differences were still present at 6 months of life. From birth to 6 months, APC underwent extensive phenotypic and functional changes in HUU and minimal changes in HEU. TLR stimulation also generated lower NK cell expression of CD69 and/or IFNγ in HEU compared with HUU at birth and 6 months. In vitro experiments showed that NK IFNγ expression depended on APC cytokine secretion in response to TLR stimulation. Ex vivo IL10 supplementation decreased APC-mediated NK cell activation measured by IFNγ expression. We conclude that APC maturation was stunted or delayed in the first 6 months of life in HEU compared with HUU. Deficient inflammatory APC responses and/or the imbalance between inflammatory and regulatory responses in HEU may play an important role in their increased susceptibility to severe infections.

Upper airway gene expression shows a more robust adaptive immune response to SARS-CoV-2 in children.

Unlike other respiratory viruses, SARS-CoV-2 disproportionately causes severe disease in older adults whereas disease burden in children is lower. To investigate whether differences in the upper airway immune response may contribute to this disparity, we compare nasopharyngeal gene expression in 83 children (<19-years-old; 38 with SARS-CoV-2, 11 with other respiratory viruses, 34 with no virus) and 154 older adults (>40-years-old; 45 with SARS-CoV-2, 28 with other respiratory viruses, 81 with no virus). Expression of interferon-stimulated genes is robustly activated in both children and adults with SARS-CoV-2 infection compared to the respective non-viral groups, with only subtle distinctions. Children, however, demonstrate markedly greater upregulation of pathways related to B cell and T cell activation and proinflammatory cytokine signaling, including response to TNF and production of IFNγ, IL-2 and IL-4. Cell type deconvolution confirms greater recruitment of B cells, and to a lesser degree macrophages, to the upper airway of children. Only children exhibit a decrease in proportions of ciliated cells, among the primary targets of SARS-CoV-2, upon infection. These findings demonstrate that children elicit a more robust innate and especially adaptive immune response to SARS-CoV-2 in the upper airway that likely contributes to their protection from severe disease in the lower airway.

Congenital Co-infections Among HIV-Exposed Infants Born to Mothers on Antiretroviral Treatment in the United States.

Background: Many women living with HIV (WLHIV) are co-infected with cytomegalovirus (CMV), Toxoplasma gondii (T gondii), and/or hepatitis C virus (HCV). The rates of congenital or perinatal transmission of these co-infections are not well defined in the current era, when most WLHIV receive antiretroviral therapy (ART) during pregnancy. Methods: Retrospective review of infants of WLHIV born between 2009-2019. Mothers were screened for antibodies to CMV, T. gondii, and HCV; chronic HCV infection was confirmed using plasma RNA PCR. Infants whose mothers had positive/unknown serostatus were screened for CMV using urine or saliva DNA PCR or culture at ≤3 weeks of life; T. gondii using serology at ≤1 month; and HCV using plasma RNA PCR at ≤6 months and serology at ≥12 months. Results: The study included 264 infants from 255 pregnancies in 191 mothers. At delivery, the median (IQR) CD4 count was 569 (406-748) cells/mm3 and plasma HIV load was 0 (0-24) RNA copies/mL. Among 243 infants born to CMV-seropositive (209) or CMV-missed serostatus (25) mothers, 163 (67.1%) were tested for CMV. Four infants had CMV detected, resulting in a rate of congenital infection of 2.5%. Among 65 infants from 54 (21.2%) pregnancies in T. gondii-seropositive women and 8 in women with unknown T. gondii-serostatus, one acquired congenital toxoplasmosis in the setting of acute maternal T. gondii infection. There were no episodes of vertical transmission from mothers with latent toxoplasmosis. Among 18 infants from 13 (5.1%) pregnancies in HCV RNA PCR-positive women and 4 in women with unknown HCV serostatus, there were no congenital or perinatal HCV transmissions. Conclusions: In a US cohort of pregnant WLHIV on ART, we identified high maternal CMV seroprevalence and a high rate of congenital CMV infection. We did not identify any congenital or perinatal transmissions of T. gondii or HCV among mothers who had latent or chronic infections. Our data support screening pregnant WLHIV and their infants for CMV and suggest that the rates of congenital and perinatal T. gondii and HCV infections among infants born to WLHIV on ART may be lower in the era of effective ART.

The phytochemical diversity of commercial Cannabis in the United States.

The legal status of Cannabis is changing, fueling an increasing diversity of Cannabis-derived products. Because Cannabis contains dozens of chemical compounds with potential psychoactive or medicinal effects, understanding this phytochemical diversity is crucial. The legal Cannabis industry heavily markets products to consumers based on widely used labeling systems purported to predict the effects of different "strains." We analyzed the cannabinoid and terpene content of commercial Cannabis samples across six US states, finding distinct chemical phenotypes (chemotypes) which are reliably present. By comparing the observed phytochemical diversity to the commercial labels commonly attached to Cannabis-derived product samples, we show that commercial labels do not consistently align with the observed chemical diversity. However, certain labels do show a biased association with specific chemotypes. These results have implications for the classification of commercial Cannabis, design of animal and human research, and regulation of consumer marketing-areas which today are often divorced from the chemical reality of the Cannabis-derived material they wish to represent.

Immunologic and Virologic Factors Associated With Hospitalization in Human Immunodeficiency Virus-Exposed, Uninfected Infants in the United States.

BACKGROUND: Human immunodeficiency virus (HIV)-exposed, uninfected (HEU) infants experience higher rates of morbidity and mortality than HIV-unexposed, uninfected (HUU) infants. Few studies have examined whether particular infections and/or immune responses are associated with hospitalization among HEU infants born in the United States. METHODS: We evaluated a subset of HEU infants enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group P1025 and/or Pediatric HIV/AIDS Cohort Study Surveillance Monitoring for ART Toxicities studies. We determined seroconversion to 6 respiratory viruses and measured antibody concentrations to 9 vaccine antigens using quantitative ELISA or electrochemiluminescence. Multivariable modified Poisson regression models were fit to evaluate associations of seroconversion to each respiratory virus/family and antibody concentrations to vaccine antigens with risk of hospitalization in the first year of life. Antibody concentrations to vaccine antigens were compared between HEU infants and HUU infants from a single site using multivariable linear regression models. RESULTS: Among 556 HEU infants, seroconversion to respiratory syncytial virus (RSV) and parainfluenza was associated with hospitalization (adjusted risk ratio, 1.95 [95% CI, 1.21-3.15] and 2.30 [1.42-3.73], respectively). Antibody concentrations to tetanus toxoid, pertussis, and pneumococcal vaccine antigens were higher among 525 HEU compared with 100 HUU infants. No associations were observed between antibody concentrations with any vaccine and hospitalization among HEU infants. CONCLUSIONS: RSV and parainfluenza contribute to hospitalization among HEU infants in the first year of life. HEU infants demonstrate robust antibody responses to vaccine antigens; therefore, humoral immune defects likely do not explain the increased susceptibility to infection observed in this population.

Risk Factors for Severe COVID-19 in Children.

BACKGROUND: There are limited pediatric data regarding severe COVID-19 disease. Our study aims to describe the epidemiology and identify risk factors for severe COVID-19 disease in children. METHODS: This is a retrospective cohort study among children with positive SARS-CoV-2 PCR from March to July 2020 at Children's Hospital Colorado. Risk factors for severe disease were analyzed as defined by hospital admission, respiratory support, or critical care. Univariable and multivariable analyses were conducted. RESULTS: Among 454 patients identified with SARS-CoV-2, 191 (42.1%) were females, median age 11 years. Fifty-five percent of all patients identified as Hispanic compared with 29% among all hospital visits in 2019 (P < 0.0001). In multivariable analyses, age 0-3 months or >20 years [adjusted odds ratio (aOR), 7.85; P < 0.0001 and aOR, 5.1; P = 0.03, respectively], preterm birth history (aOR, 3.7; P = 0.03), comorbidities [including immunocompromise (aOR, 3.5; P = 0.004), gastrointestinal condition (aOR, 2.7; P = 0.009), diabetes (aOR, 6.6; P = 0.04), asthma (aOR, 2.2; P = 0.04)], and specific symptoms at presentation were predictors for admission. Age 0-3 months or >20 years, asthma, gastrointestinal condition, and similar symptoms at presentation were also predictors for respiratory support. Elevated C-reactive protein was associated with the need for critical care with median of 17.7 mg/dL (IQR, 5.3-22.9) versus 1.95 mg/dL (IQR, 0.7-5.5) among patients requiring critical versus no critical care (OR, 1.2; P = 0.02). CONCLUSIONS: Extremes of age, comorbid conditions, and elevated CRP are predictors of severe disease in children. Findings from this study can inform pediatric providers and public health officials to tailor clinical management, pandemic planning, and resource allocation.

Child HIV Exposure and CMV Seroprevalence in Botswana: No Associations With 24-Month Growth and Neurodevelopment.

BACKGROUND: We sought to identify predictors of child cytomegalovirus (CMV) infection overall and by maternal HIV status and to assess associations of child CMV status with growth and neurodevelopmental outcomes at 24 months of age in Botswana. METHODS: Data and samples were used from the Botswana-based observational Tshipidi study (2010-2014), enrolling pregnant women living with and without HIV and following their infants through 2 years of age. Child plasma samples were tested at 18 months of age for anti-CMV immunoglobulin G (IgG). Associations were assessed between detectable anti-CMV IgG and growth (using the World Health Organization Child Growth Standards) and neurodevelopment (using the Bayley Scales of Infant and Toddler Development III and the Developmental Milestones Checklist) at 24 months of age. RESULTS: Of 317 children, 215 (68%) had detectable anti-CMV IgG at 18 months of age. Comparatively, 83% (n = 178) of HIV-unexposed uninfected (HUU) children had positive CMV serology vs 47% (n = 139) of HIV-exposed uninfected (HEU) children (P < .01); 100% of HUU vs 10.5% of HEU children breastfed. Child CMV infection was not associated with weight-for-age, weight-for-length, or length-for-age z-scores at 24 months. In HUU children, CMV infection was associated with smaller head circumference (P < .01). No difference was observed by child CMV status in any neurodevelopmental domain at 24 months. CONCLUSIONS: We observed high CMV seropositivity in 18-month-old children in Botswana, with higher seropositivity among breastfed (HUU) children. Positive CMV serostatus was not associated with 24-month child growth or neurodevelopmental outcomes, with the exception of smaller head circumference among HUU CMV-positive children.

Comparison of Upper Respiratory Viral Load Distributions in Asymptomatic and Symptomatic Children Diagnosed with SARS-CoV-2 Infection in Pediatric Hospital Testing Programs.

The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were (i) adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay and (ii) converted to estimated VL (numbers of copies per milliliter) using internal or manufacturer data. Adjusted Ct values and estimated VL for asymptomatic versus symptomatic children (118 asymptomatic versus 197 symptomatic children aged 0 to 4 years, 79 asymptomatic versus 97 symptomatic children aged 5 to 9 years, 69 asymptomatic versus 75 symptomatic children aged 10 to 13 years, 73 asymptomatic versus 109 symptomatic children aged 14 to 17 years) were compared. The median adjusted Ct value for asymptomatic children was 10.3 cycles higher than for symptomatic children (P < 0.0001), and VL were 3 to 4 logs lower than for symptomatic children (P < 0.0001); differences were consistent (P < 0.0001) across all four age brackets. These differences were consistent across all institutions and by sex, ethnicity, and race. Asymptomatic children with diabetes (odds ratio [OR], 6.5; P = 0.01), a recent contact (OR, 2.3; P = 0.02), and testing for surveillance (OR, 2.7; P = 0.005) had higher estimated risks of having a Ct value in the lowest quartile than children without, while an immunocompromised status had no effect. Children with asymptomatic SARS-CoV-2 infection had lower levels of virus in their nasopharynx/oropharynx than symptomatic children, but the timing of infection relative to diagnosis likely impacted levels in asymptomatic children. Caution is recommended when choosing diagnostic tests for screening of asymptomatic children.

Human Immunodeficiency Virus Exposure but Not Early Cytomegalovirus Infection Is Associated With Increased Hospitalization and Decreased Memory T-Cell Responses to Tetanus Vaccine.

BACKGROUND: Human immunodeficiency virus (HIV)-exposed, uninfected (HEU) infants experience high rates of infectious morbidity. We hypothesized that early cytomegalovirus (CMV) infection was associated with increased hospitalization rates and decreased vaccine responses in HEU compared with HIV-unexposed (HUU) infants. METHODS: Among infants enrolled in the Tshipidi study in Botswana, we determined CMV infection status by 6 months of age and compared hospitalization rates and responses to tetanus and Bacille Calmette-Guérin vaccines among HEU and HUU vaccinees. RESULTS: Fifteen of 226 (6.6%) HEU infants and 17 (19.3%) of 88 HUU infants were CMV-infected by 6 months. The HEU infants were approximately 3 times as likely to be hospitalized compared with HUU infants (P = .02). The HEU peripheral blood cells produced less interleukin (IL)-2 (P = .004), but similar amounts of interferon-γ, after stimulation with tetanus toxoid. Antitetanus immunoglobulin G titers were similar between groups. Cellular responses to purified protein derivative stimulation did not differ between groups. Maternal receipt of 3-drug antiretroviral therapy compared with zidovudine was associated with increased IL-2 expression after tetanus toxoid stimulation. The infants' CMV infection status was not associated with clinical or vaccine response outcomes. CONCLUSIONS: We observed that increased rates of hospitalization and decreased memory T-cell responses to tetanus vaccine were associated with HIV exposure and incomplete treatment of maternal HIV infection, but not early CMV infection.

Rates of Hospitalization and Infection-Related Hospitalization Among Human Immunodeficiency Virus (HIV)-Exposed Uninfected Children Compared to HIV-Unexposed Uninfected Children in the United States, 2007-2016.

BACKGROUND: Studies from multiple countries have suggested impaired immunity in perinatally human immunodeficiency virus (HIV)-exposed uninfected children (HEU), with elevated rates of all-cause hospitalization and infections. We estimated and compared the incidence of all-cause hospitalization and infection-related hospitalization in the first 2 years of life among HEU and HIV-unexposed uninfected children (HUU) in the United States. Among HEU, we evaluated associations of maternal HIV disease-related factors during pregnancy with risk of child hospitalization. METHODS: HEU data from subjects enrolled in the Surveillance Monitoring for Antiretroviral Therapy Toxicities Study (SMARTT) cohort who were born during 2006-2017 were analyzed. HUU comparison data were obtained from the Medicaid Analytic Extract database, restricted to states participating in SMARTT. We compared rates of first hospitalization, total hospitalizations, first infection-related hospitalization, total infection-related hospitalizations, and mortality between HEU and HUU using Poisson regression. Among HEU, multivariable Poisson regression models were fitted to evaluate associations of maternal HIV factors with risk of hospitalization. RESULTS: A total of 2404 HEU and 3 605 864 HUU were included in the analysis. HEU children had approximately 2 times greater rates of first hospitalization, total hospitalizations, first infection-related hospitalization, and total infection-related hospitalizations compared with HUUs. There was no significant difference in mortality. Maternal HIV disease factors were not associated with the risk of child infection or hospitalization. CONCLUSIONS: Compared with HUU, HEU children in the United States have higher rates of hospitalization and infection-related hospitalization in the first 2 years of life, consistent with studies in other countries. Closer monitoring of HEU infants for infection and further elucidation of immune mechanisms is needed.

Disseminated Histoplasmosis as an AIDS-Defining Illness Presenting as Fever of Unknown Origin in an 11-Year-Old Female.

A previously healthy 11-year-old female, who emigrated from Central America four years prior, was admitted with eight days of fever, night sweats, and anorexia. Past medical history included severe bronchiolitis, varicella, and hepatitis A as a child. Upon admission, her physical exam was significant for nontender cervical lymphadenopathy, intermittent erythematous papules on the upper extremities, and mild abdominal tenderness. Initial laboratory studies revealed leukopenia, anemia, elevated inflammatory markers, and antibodies to HIV-1 in the patient's serum and cerebrospinal fluid. Computed tomography scan was remarkable for many small nodules throughout the lungs and widespread lymphadenopathy. Additional testing confirmed the diagnosis of HIV/AIDS with a CD4 count of 52 cells/mm3, complicated by disseminated histoplasmosis. This case is significant because it represents a late presentation of vertically transmitted HIV with disseminated histoplasmosis in a nonendemic region as the AIDS-defining illness. This highlights the importance of maintaining a broad differential for opportunistic infections, especially among those who have spent a significant amount of time in a country where unusual pathogens may be more common. This case also considers the utility of antigen testing as a sensitive diagnostic test in immunocompromised patients.

The relationship between alpha asymmetry and ADHD depends on negative affect level and parenting practices.

Atypical frontal alpha asymmetry is associated with the approach/withdrawal and affective processes implicated in many psychiatric disorders. Rightward alpha asymmetry, associated with high approach, is a putative endophenotype for attention deficit/hyperactivity disorder (ADHD). However, findings are inconsistent, likely because of a failure to consider emotional heterogeneity within the ADHD population. In addition, how this putative risk marker interacts with environmental factors known to increase symptom severity, such as parenting practices, has not been examined. The current study examined patterns of alpha asymmetry in a large sample of adolescents with and without ADHD, including the moderating role of negative affect and inconsistent discipline. Resting-state EEG was recorded from 169 well-characterized adolescents (nADHD = 79). Semi-structured clinical interviews and well-validated rating scales were used to create composites for negative affect and inconsistent discipline. The relationship between alpha asymmetry and ADHD diagnosis was moderated by negative affect. Right asymmetry was present only for those with ADHD and low levels of negative affect. In addition, greater right alpha asymmetry predicted severity of ADHD symptoms for those with the disorder, but only in the context of inconsistent parenting practices. Results confirm right alpha asymmetry is a possible endophenotype in ADHD but highlight the need to consider emotional heterogeneity and how biological risk interacts with child environment in order to fully characterize its relationship to disorder liability and severity.

Cytomegalovirus Viremia in HIV-1 Subtype C Positive Women at Delivery in Botswana and Adverse Birth/Infant Health Outcomes.

BACKGROUND: We evaluated the association between maternal cytomegalovirus (CMV) viremia during pregnancy and adverse birth and infant health outcomes in HIV-infected mothers and their HIV-exposed uninfected infants. METHODS: HIV-positive women and their infants were followed prospectively from pregnancy through 2 years postpartum in the "Tshipidi" study in Botswana. We analyzed the association between detectable CMV DNA in maternal blood at delivery and adverse birth outcomes (stillbirth, preterm delivery, small for gestational age, or birth defect), as well as infant hospitalization and mortality through 24 months. RESULTS: We measured CMV DNA in blood samples from 350 (77.1%) of 454 HIV-positive women from the Tshipidi study. The median maternal CD4 count was 422 cells/mL, and median HIV-1 RNA at entry was 3.2 log10 copies/mL. Fifty-one (14.6%) women had detectable CMV DNA. In unadjusted analyses, detectable CMV DNA was associated with higher maternal HIV-1 RNA [odds ratio (OR) 1.4, 95% confidence interval (CI): 1.1 to 1.9], presence of a birth defect (OR 9.8, 95% CI: 1.6 to 60.3), and occurrence of any adverse birth outcome (OR 2.0, 95% CI: 1.04 to 3.95). In multivariable analysis, we observed a trend toward association between detectable maternal CMV DNA and occurrence of any adverse birth outcome (adjusted OR 1.9, 95% CI: 0.96 to 3.8). Maternal CMV viremia was not associated with infant hospitalization and/or death by 24 months. CONCLUSIONS: Approximately 1 in 6 HIV-positive women in Botswana had detectable CMV DNA in blood at delivery. The presence of maternal CMV viremia had a borderline association with adverse birth outcomes but not with 24-month morbidity or mortality in HIV-exposed uninfected children.

Factors Associated with Lower Respiratory Tract Infections in HIV-Exposed Uninfected Infants.

To identify factors that predispose human immunodeficiency virus (HIV)-exposed uninfected infants (HEUs) to higher incidence of severe infections, hospitalization, and death in the first 6-24 months of life compared with HEUs with and without lower respiratory tract infection (LRTI) in the first 6 months of life. Nested case-control study of 107 LRTI+ infants enrolled in the International Site Development Initiative (NISDI) Perinatal and Longitudinal Study in Latin American Countries (LILAC) studies with and 140 LRTI- in the first 6 months, matched by date and place of birth. Infants and mothers had plasma antibodies measured against respiratory syncytial virus (RSV), parainfluenza (PIV) 1, 2, 3, influenza, and pneumococcus 1, 5, 6B, and 14. Compared with LRTI-, mothers of LRTI+ HEUs had lower years of education, lower CD4+ cells, and higher HIV plasma viral load at delivery, but similar use of antiretrovirals and cotrimoxazole and other sociodemographic characteristics. LRTI+ and LRTI- HEUs had similar demographic and hematological characteristics and antibody concentrations against respiratory pathogens at birth. At 6 months, the rates of seroconversions to respiratory pathogens and antibody responses to tetanus vaccine were also similar. However, antibody concentrations to RSV were significantly higher in LRTI+ compared with LRTI- HEUs and marginally higher to PIV1. Maternal factors associated with advanced HIV disease, but unrelated to the use of antiretrovirals, cotrimoxazole, or the level of maternal antibodies against respiratory pathogens, contribute to the increased risk of LRTI in HEUs. In HEUs, antiretroviral and cotrimoxazole use, exposure to respiratory pathogens and humoral immune responses were not associated with the incidence of LRTI.