Safety, Tolerability, and Pharmacokinetics of a Long-Acting Broadly Neutralizing Human Immunodeficiency Virus Type 1 (HIV-1) Monoclonal Antibody VRC01LS in HIV-1-Exposed Newborn Infants.

BACKGROUND: Perinatal human immunodeficiency virus type 1 (HIV-1) continues to occur due to barriers to effective antiretroviral prevention that might be mitigated by long-acting broadly neutralizing monoclonal antibodies (bNAbs). METHODS: An extended half-life bNAb, VRC01LS, was administered subcutaneously at 80 mg/dose after birth to HIV-1-exposed, nonbreastfed (cohort 1, n = 10) and breastfed (cohort 2, n = 11) infants. Cohort 2 received a second dose (100 mg) at 12 weeks. All received antiretroviral prophylaxis. VRC01LS levels were compared to VRC01 levels determined in a prior cohort. RESULTS: Local reactions (all grade ≤2) occurred in 67% and 20% after dose 1 and dose 2, respectively. The weight-banded dose (mean 28.8 mg/kg) of VRC01LS administered subcutaneously achieved a mean (standard deviation) plasma level of 222.3 (71.6) µg/mL by 24 hours and 44.0 (11.6) µg/mL at week 12, prior to dose 2. The preestablished target of ≥50 µg/mL was attained in 95% and 32% at weeks 8 and 12, respectively. The terminal half-life was 37-41 days. VRC01LS level after 1 dose was significantly greater (P <.002) than after a VRC01 dose (20 mg/kg). No infants acquired HIV-1. CONCLUSIONS: VRC01LS was well tolerated with pharmacokinetics that support further studies of more potent long-acting bNAbs as adjunct treatment with antiretrovirals to prevent infant HIV-1 transmission.

Recruitment of Youth Living With HIV to Optimize Adherence and Virologic Suppression: Testing the Design of Technology-Based Community Health Nursing to Improve Antiretroviral Therapy (ART) Clinical Trials.

BACKGROUND: Despite advances in HIV diagnosis and treatment, adolescents and young adults 12-25 years old have high HIV incidence, poor engagement and retention in treatment, and low rates of adherence and virologic suppression when compared to their older counterparts. HIV has emerged as a chronic disease for which antiretroviral therapy (ART) adherence is critical for virologic suppression and long-term survival. Virologic suppression has been elusive for many youth with HIV (YHIV). Novel strategies designed to facilitate health care systems' support for YHIV between medical visits are essential for improving ART adherence, virologic suppression, and long-term survival. OBJECTIVE: The aim of this study is to compare the effectiveness of a technology-enhanced community health nursing intervention (TECH2CHECK) to a standard of care (SOC) control group for improving ART adherence and subsequent viral suppression using a randomized trial design. The objectives are to assess the feasibility, acceptability, and cost-effectiveness of TECH2CHECK as compared to SOC for management of HIV in the outpatient setting and to examine the sustainability of self-care behavior, adherence, and virologic suppression among youth following the intervention period. METHODS: We will recruit 120 adherence-challenged YHIV being followed at clinics specializing in HIV care in the Baltimore-Washington metropolitan area and in Jacksonville. Eligible participants complete an audio, computer-assisted self-interview and are randomized to either TECH2CHECK intervention or the SOC (60 participants in each arm). The primary outcome of interest is virologic suppression (viral load <20 copies/mL) and improved treatment adherence. Participants in the intervention arm receive community health nursing visits at 2 weeks, 6 weeks, 10 weeks, 14 weeks, and 26 weeks. The intervention arm also receives SMS messaging comprising daily adherence and appointment reminders and positive reinforcement for medication adherence daily for 2 weeks, on alternate days for 2 weeks, thrice weekly for 1 month, weekly for 3 months, and every 2 weeks for the rest of the study duration. The control group receives appointment reminders and SOC per clinic protocol. Exploratory analysis will be conducted to determine differences in medication adherence and virologic suppression in the 2 arms and to assess cost-effectiveness and study feasibility and acceptability. RESULTS: In the first 23 months of the study (July 2018-April 2020), 56 (55%) of 102 eligible patients were enrolled and randomized. At present, participating youths are primarily African American (53/56, 95%), male (37/56, 66%), and ≥18 years old (53/56, 95%). Follow-up study visits, as required per the protocol, have been completed by 77% (43/56), 94% (45/48), 95% (37/39), 96% (24/25), and 100% (10/10) of participants at the 1-month, 3-month, 6-month, 12-month, and 18-month follow-ups, respectively. CONCLUSIONS: Preliminary accrual and retention data suggest that TECH2CHECK is feasible and acceptable. TRIAL REGISTRATION: ClinicalTrials.gov NCT03600103 https://clinicaltrials.gov/ct2/show/NCT03600103. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/23480.

The Relationship Between Individual Characteristics and Interest in Using a Mobile Phone App for HIV Self-Management: Observational Cohort Study of People Living With HIV.

BACKGROUND: The human immunodeficiency virus (HIV) continues to be a major health issue in the United States, and an estimated 1.2 million people in the United States are living with HIV. As part of Healthy People 2020, the Office of Disease Prevention and Health Promotion has targeted the persistent demographic and geographic disparities in HIV prevalence and management. Preliminary evidence suggests that mobile health technology (smartphone apps) may be a promising way to support HIV self-management among vulnerable populations of people living with HIV (PLWH) who lack access to appropriate health care services. OBJECTIVE: This study examines the association between individual characteristics of PLWH and level of interest in using a free mobile phone app for HIV self-management. METHODS: This study was conducted using cross-sectional survey data collected in the Florida Cohort Study between 2014 and 2016 (N=766). Associations between individual characteristics of PLWH and level of interest in using a free mobile phone app for HIV self-management were examined using bivariate analysis and logistic regression. RESULTS: Overall, 85.5% (655/766) of respondents were interested in using a free mobile phone app that supports HIV self-management. Participants expressed the highest interest in app functions that facilitate communication with health care providers (568/740, 76.8%) or help to identify relevant health care services (556/745 74.6%). Age (OR 0.959, 95% CI 0.936-0.982), education (OR 1.281, 95% CI 1.027-1.598) and disability or inability to work (OR 0.296, 95% CI 0.145-0.606) were all significantly associated with being interested in using a free mobile phone app for HIV self-management. CONCLUSIONS: This study indicates that a majority of PLWH are interested in using a free mobile phone app to self-manage their condition. The findings can inform the development of mobile phone apps that support effective HIV self-management.

Community-engaged strategies to promote hepatitis B testing and linkage to care in immigrants of Florida.

To improve early identification and linkage to treatment and preventive services for hepatitis B virus (HBV) in persons born in countries with intermediate or high (>2%) HBV prevalence, the University of Florida Center for HIV/AIDS Research, Education, and Services (UF CARES) employed community-engaged strategies to implement the Hepatitis B Awareness and Service Linkage (HBASL) program. In this brief report, we present a summary of program components, challenges, and successes. Faith and community-based networks were established to improve HBV testing and screening and to increase foreign born nationals (FBNs) access to HBV care. A total of 1516 FBNs were tested and screened for hepatitis B. The majority were females (50.4%), Asians (62.8%), non-Hispanic (87.2%), and they also received post-test counseling (54.8%). Noted program advantages included the development of community networks and outreach to a large population of FBNs. The major challenges were institutional delays, pressures related to meeting program deliverables, and diversity within FBNs populations. Community health workers in the United States can replicate this program in their respective communities and ensure success by maintaining a strong community presence, establishing partnerships and linkage processes, developing a sustainability plan, and ensuring the presence of dedicated program staff.

Salmonella Infections in Childhood.

Salmonella are gram-negative bacilli within the family Enterobacteriaceae. They are the cause of significant morbidity and mortality worldwide. Animals (pets) are an important reservoir for nontyphoidal Salmonella, whereas humans are the only natural host and reservoir for Salmonella Typhi. Salmonella infections are a major cause of gastroenteritis worldwide. They account for an estimated 2.8 billion cases of diarrheal disease each year. The transmission of Salmonella is frequently associated with the consumption of contaminated water and food of animal origin, and it is facilitated by conditions of poor hygiene. Nontyphoidal Salmonella infections have a worldwide distribution, whereas most typhoidal Salmonella infections in the United States are acquired abroad. In the United States, Salmonella is a common agent for food-borne­associated infections. Several outbreaks have been identified and are most commonly associated with agricultural products. Nontyphoidal Salmonella infection is usually characterized by a self-limited gastroenteritis in immunocompetent hosts in industrialized countries, but it may also cause invasive disease in vulnerable individuals (eg, children less than 1 year of age, immunocompromised). Antibiotic treatment is not recommended for treatment of mild to moderate gastroenteritis by nontyphoidal Salmonella in immunocompetent adults or children more than 1 year of age. Antibiotic treatment is recommended for nontyphoidal Salmonella infections in infants less than 3 months of age, because they are at higher risk for bacteremia and extraintestinal complications. Typhoid (enteric) fever and its potential complications have a significant impact on children, especially those who live in developing countries. Antibiotic treatment of typhoid fever has become challenging because of the emergence of Salmonella Typhi strains that are resistant to classically used first-line agents: ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol. The choice of antibiotics for the management of typhoid fever should be guided by the local resistance pattern. Recommendations include using an extended spectrum cephalosporin, azithromycin, or a fluoroquinolone. Fecal carriage of Salmonella is an important factor in the spread of the organism to healthy individuals. The most important measures to prevent the spread and outbreaks of Salmonella infections and typhoid fever are adequate sanitation protocols for food processing and handling as well as hand hygiene. In the United States, 2 vaccines are commercially available against Salmonella Typhi. The WHO recommends the use of these vaccines in endemic areas and for outbreak control.

Pediatric HIV Infection.

As this article was written, celebrating another World AIDS Day, which falls on December 1 each year, was just days away. Not only is this a time to reflect on all the success with the treatment and management of HIV infection, in particular MTCT but also a time to reflect on the challenges ahead. As champions of children, pediatricians need to be more vocal in educating patients, families, and their communities about the risks of sexually transmitted infections and HIV infection and the need for testing as part of routine primary care. This needs to be the norm rather than the exception. All persons should be aware of their HIV status; until and unless this approach is taken, new infections will continue to be seen in young people, and even those who are aware of their status will continue to be wary of seeking care.

Renal microabscesses due to Bartonella infection.

We report a case of cat scratch disease with bilateral renal microabscesses. This case is unique in that there were no other abscesses found intrabdominally. A previously healthy child was admitted with a 12-day history of fever and headaches. Bartonella henselae titers were initially IgG 1:640 and IgM 1:100, and later IgG >1:2560 and IgM >1:800. An abdominal ultrasound examination was normal but CT scan revealed microabscesses in both kidneys.

Impact of protease inhibitor substitution with efavirenz in HIV-infected children: results of the First Pediatric Switch Study.

OBJECTIVE: Simplification of antiretroviral regimen in human immunodeficiency virus (HIV)-infected children has not yet been investigated. In general, children have a more difficult time maintaining viral suppression because of many factors, including frequent nonadherence and less availability of antiretrovirals in palatable forms. In addition, many serious metabolic complications have emerged in HIV-infected adults and are believed to be attributable to antiretroviral therapy. Some of these complications--hypercholesterolemia, hypertriglyceridemia, and insulin resistance--are believed to be the result of the use of protease inhibitor (PI) therapy, whereas the cause of others, such as lipodystrophy, remains undetermined. Recent reports underline that children experience long-term metabolic abnormalities in the same manner that adults do, and perhaps these consequences are even more worrisome in children secondary to long-term expected survival. We report here the results of the first open-label PI-switch study in HIV-infected children. METHODS: Seventeen children, 24 to 160 months of age (median: 120), were enrolled into the study. All were receiving a stable PI-containing antiretroviral regimen that containing 2 to 3 nucleoside analogue reverse transcriptase inhibitors (NRTIs) in addition to 1 to 2 PIs for a median duration of 21 months (range: 5-50) before study entry. All children had HIV-1 RNA <400 copies/mL at screening; their baseline plasma HIV-1 RNA level had been <400 copies/mL for a median of 13 months (range: 4-55) before study entry. All patients were naïve to nonnucleoside reverse transcriptase inhibitor therapy. Their protease inhibitor(s) was switched to efavirenz while their NRTI therapy was maintained. RESULTS: All children were heavily pretreated; 88% of the patients had previous NRTIs, and 41% had previous PI use. The most common PI at study entry was nelfinavir (47%), followed by ritonavir (29%), then amprenavir (18%); only 1 was on saquinavir/ritonavir. At study entry, the duration of previous antiretroviral therapy was between 21 and 123 months (median: 88). All patients completed the 48-week study. No acquired immunodeficiency syndrome-defining events occurred. There were no rashes and no changes in liver transaminases. Mild, transient insomnia and dizziness each occurred in 1 child. Two other subjects (6 and 8 years old) experienced unusual vivid dreams, mostly pleasant, which decreased in intensity and frequency after the first 12 weeks of the study. One subject, a 10-year-old girl, had an episode of generalized seizure at week 6; study drugs were not interrupted, and seizure never recurred. The patient had a strong family history of epilepsy, although she had never experienced previous seizures. No anticonvulsants were given. Sixteen of 17 patients had HIV-1 RNA levels of <50 copies/mL (1 HIV-1 RNA was 61 copies/mL) at week 48. The mean CD4% remained stable initially from a mean of 35.1% (+/-2.8%) at baseline to 36.8% (+/-5%) at week 24, but increased to 38% (+/-6%) at week 48. Fasting triglycerides decreased from a mean of 126 mg/dL (+/-50) at baseline to 86 mg/dL (+/-45) at week 24 and to 94 mg/dL (+/-38) at week 48. At study entry, 12 (71%) of 17 children had triglyceride levels greater than the 95th percentile for age, race, and gender, compared with only 6 (35%) of 17 at week 48. Fasting cholesterol levels decreased from a mean of 203 mg/dL (+/-50) at baseline to 173 mg/dL (+/-31) at week 24 and to 174 mg/dL (+/-27) at week 48. At study entry, 5 (29%) of 17 children had cholesterol levels greater than the 95th percentile for age, race, and gender, compared with only 1 (6%) of 17 at week 48. The decrease in low-density lipoprotein cholesterol was also significant, from a mean baseline of 124 mg/dL (+/-42) to 100 mg/dL (+/-28) at week 24 and to 105 mg/dL (+/-20) at week 48. High-density lipoprotein (HDL) cholesterol did not change significantly, but the changes in cholesterol:HDL ratio, a better marker of atherogenic risk, significantly decreased from a mean baseline of 3.8 (+/-0.8) to 3.2 (+/-0.7) at week 24 and to 3 (+/-0.6) at week 48. Detailed dietary history revealed no significant changes during the study. In addition, none of the patients initiated therapy with lipid-lowering agents. There were no significant changes in insulin or C-peptide throughout the study period. In addition, anthropometric measurements that included mid-thigh and mid-arm circumferences, triceps and thigh skinfolds, and waist:hip ratio were stable throughout the study period. For bioelectrical impedance measurements, lean body mass increased from a mean baseline of 32.1 lb (+/-9.3) to 35.7 lb (+/-11.4) at week 24 and to 36.5 lb (+/-11.5) at week 48. Bioelectrical impedance measurements of fat content were unchanged throughout the study period. CONCLUSION: This is the first study in children to evaluate the substitution of PI in a virologically successful regimen with efavirenz, a potent once-daily nonnucleoside reverse transcriptase inhibitor therapy. We were able to show significant improvement in fasting total cholesterol, low-density lipoprotein cholesterol, triglycerides, and, more important, the cholesterol:HDL ratio. In addition, switching to an efavirenz-containing regimen was well tolerated and successfully maintained virologic suppression in all HIV-infected children in this study. This study should encourage large randomized trials to investigate simplification strategies in HIV-infected children.

The impact of race/ethnicity on mother-to-child HIV transmission in the United States in Pediatric AIDS Clinical Trials Group Protocol 316.

The present analysis was designed to determine whether race/ethnicity was independently associated with mother-to-child HIV-1 transmission risk in subjects enrolled in a trial of 2-dose intra-partum nevirapine in combination with standard antiretroviral therapy and to determine what factors, including race/ethnicity, predicted maternal viral suppression at the time of delivery. Women enrolled in Pediatric AIDS Clinical Trials Group (PACTG) 316 from sites in the United States and Puerto Rico were included. Distribution of selected maternal disease and treatment characteristics was assessed by race/ethnicity category. Logistic regression models were fit to evaluate possible association of factors with HIV transmission and with viral load at delivery. Variables associated with the outcome at P < 0.05 level were retained in the final models. Of 1052 women randomized at PACTG sites, 891 were included in the present analysis: 572 (64%) were black; 206 (23%) were Hispanic; and 113 (13%) were white. All women who had infected infants were black or Hispanic (11/572 and 3/206, respectively), whereas none of the women identified as white had an infected infant (0/113). This difference was not statistically significant (P = 0.54). White women had higher entry CD4 cell counts and lower HIV-1 RNA at delivery than women of other races/ethnicities. Black and Hispanic women were more likely than white women to start therapy during their current pregnancy but did not initiate prenatal care later. In bivariate models that included antiretroviral type and variables that had values of P < or = 0.25 in univariate analysis, time of antiretroviral initiation, time of prenatal care initiation, and race/ethnicity each retained significance in predicting viral suppression at delivery. Race/ethnicity remained predictive of viral suppression at delivery in a multivariate model incorporating all of these variables (P = 0.01). Higher HIV-1 RNA and lower CD4 cell counts in women identified as black or Hispanic have significant implications for the health of these women and their newborns. Race/ethnicity is significant in predicting viral suppression at the time of delivery.