Association of Age and Pediatric Household Transmission of SARS-CoV-2 Infection.

Importance: As a result of low numbers of pediatric cases early in the COVID-19 pandemic, pediatric household transmission of SARS-CoV-2 remains an understudied topic. Objective: To determine whether there are differences in the odds of household transmission by younger children compared with older children. Design, Setting, and Participants: This population-based cohort study took place between June 1 and December 31, 2020, in Ontario, Canada. Private households in which the index case individual of laboratory-confirmed SARS-CoV-2 infection was younger than 18 years were included. Individuals were excluded if they resided in apartments missing suite information, in households with multiple index cases, or in households where the age of the index case individual was missing. Exposures: Age group of pediatric index cases categorized as 0 to 3, 4 to 8, 9 to 13, and 14 to 17 years. Main Outcomes and Measures: Household transmission, defined as households where at least 1 secondary case occurred 1 to 14 days after the pediatric index case. Results: A total of 6280 households had pediatric index cases, and 1717 households (27.3%) experienced secondary transmission. The mean (SD) age of pediatric index case individuals was 10.7 (5.1) years and 2863 (45.6%) were female individuals. Children aged 0 to 3 years had the highest odds of transmitting SARS-CoV-2 to household contacts compared with children aged 14 to 17 years (odds ratio, 1.43; 95% CI, 1.17-1.75). This association was similarly observed in sensitivity analyses defining secondary cases as 2 to 14 days or 4 to 14 days after the index case and stratified analyses by presence of symptoms, association with a school/childcare outbreak, or school/childcare reopening. Children aged 4 to 8 years and 9 to 13 years also had increased odds of transmission (aged 4-8 years: odds ratio, 1.40; 95% CI, 1.18-1.67; aged 9-13 years: odds ratio, 1.13; 95% CI, 0.97-1.32). Conclusions and Relevance: This study suggests that younger children may be more likely to transmit SARS-CoV-2 infection compared with older children, and the highest odds of transmission was observed for children aged 0 to 3 years. Differential infectivity of pediatric age groups has implications for infection prevention within households, as well as schools/childcare, to minimize risk of household secondary transmission. Additional population-based studies are required to establish the risk of transmission by younger pediatric index cases.

Four Weeks of Treatment With Rifaximin Fails to Significantly Alter Microbial Diversity in Rectal Samples of HIV-Infected Immune Non-Responders (ACTG A5286) Which May be Attributed to Rectal Swab Use.

INTRODUCTION: HIV-infected individuals have evidence of intestinal microbial translocation which is associated with immune activation and unfavorable clinical outcomes. Rifaximin, a non-absorbable antibiotic which reduces microbial translocation in other disease states, was shown to have a marginal beneficial effect on microbial translocation, T-cell activation, and inflammation in a multisite randomized trial (ACTG A5286; NCT01466595) of HIV-infected persons with poor immunologic recovery receiving ART. Here, we report analysis of the rectal microbiome changes associated with that trial. METHODS: HIV-1-infected individuals receiving ART with CD4-T cell count < 350cells/mm3 and viral suppression were randomized 2:1 to rifaximin or no therapy for 4 weeks. Rectal swabs were collected at baseline (pre-treatment) and at week 4 of rifaximin therapy. Genomic DNA extracted from rectal swab samples was analyzed using high throughput sequencing and quantitative PCR of bacterial 16S ribosomal RNA (rRNA) genes. RESULTS: Forty-eight HIV-infected participants (31 received rifaximin, 17 no treatment) were included. There was broad variability in the recovery of bacterial rRNA from the specimens at baseline. No major significant (FDR P < 0.05) effects of rifaximin treatment on alpha- or beta-diversity or individual taxa were observed between or within the treatment arms, with analyses conducted at taxonomic levels from phylum to genus. CONCLUSIONS: Rifaximin did not meaningfully alter the diversity or composition of the rectal microbiome of HIV-infected individuals after 4 weeks of therapy, although rectal swab specimens varied widely in their microbial load.

Vitamin D does not modulate immune-mediated bone loss during ART initiation.

BACKGROUND: Vitamin D (VitD) and calcium (Ca) supplementation attenuates antiretroviral therapy (ART)-associated bone loss, but it is unclear whether this effect is mediated through immunomodulation. METHODS: In this exploratory analysis of A5280, a 48-week, randomized, double-blind, placebo-controlled study of VitD/Ca supplementation with ART initiation, we characterized lymphocyte phenotypes and receptor activator of nuclear factor kappa-B ligand (RANKL) expression by median fluorescence intensity (MFI) at baseline and 48 weeks. Changes were evaluated within and between treatment groups by Wilcoxon signed rank and rank sum tests, respectively. Spearman correlations estimated relationships between cellular phenotypes and bone mineral density (BMD). RESULTS: Of 165 participants enrolled, 138 had samples for cellular phenotypes (64 VitD/Ca, 74 placebo). Markers of CD4, CD8 activation (CD38+HLA-DR+) declined (all P<0.001), but did not differ between arms. There was no decline in either %T-cells (CD4 and CD8) expressing RANKL or expression of RANKL by MFI. CD4 and CD8 activation markers were not correlated with BMD at baseline (r<0.15 and P>0.09 for all), but greater declines in CD4 activation correlated with greater declines in hip and spine BMD in both arms (0.25 ≤r ≤0.37, all P<0.05). A greater decline in CD8 activation was correlated with greater declines in both hip and spine BMD in the placebo arm only (hip r=0.31, P=0.009; spine r=0.25, P=0.035). CONCLUSIONS: Reductions in T-cell activation are characteristic of ART initiation, but only correlated modestly with bone loss. VitD/Ca supplementation does not appear to mitigate bone loss through modulation of immune activation or expression of RANKL. TRIAL REGISTRATION NUMBER: NCT01403051.

A Randomized, Double-blinded, Placebo-controlled Trial of Sitagliptin for Reducing Inflammation and Immune Activation in Treated and Suppressed Human Immunodeficiency Virus Infection.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have pleotropic anti-inflammatory and immune regulatory effects in addition to glucoregulation. We evaluated inflammation and immune markers in suppressed human immunodeficiency virus (HIV) infection during treatment with the DPP-4 inhibitor sitagliptin. METHODS: Virologically suppressed adults with HIV without diabetes on stable antiretroviral therapy (ART) with ≥100/µL CD4 cells were randomized to 16 weeks of sitagliptin 100 mg/day vs placebo in a multicenter trial. The primary endpoint was the change in plasma soluble CD14 (sCD14) from baseline to week 15-16. RESULTS: Ninety participants were randomized, and 42 from each arm were included in per-protocol analyses. Participants were 45% non-Hispanic white, 38% non-Hispanic black, and 15% Hispanic, with a median age of 51 years; 83% were male; and the median CD4 count was 602 cells/µL. At week 15-16, there was no difference in sCD14 change between the 2 arms (P = .69). Relative to placebo, the sitagliptin arm had 47% greater decline in CXCL10 (95% confidence interval, -57% to -35%) at week 15 (P < .001). There were no significant between-arm differences in other soluble biomarkers, total CD4 and CD8 counts, or markers of lymphocyte or monocyte activation. Sitagliptin was well tolerated. CONCLUSIONS: Sixteen weeks of sitagliptin had no effect on sCD14 levels in virologically suppressed participants with HIV. CXCL10, a chemokine involved in atherogenesis that predicts non-AIDS events during ART, declined markedly with sitagliptin. This suggests that DPP-4 inhibition has the potential to reduce cardiovascular morbidity in treated HIV infection. CLINICAL TRIALS REGISTRATION: NCT01426438.

An Evaluation of Provincial Infectious Disease Surveillance Reports in Ontario.

CONTEXT: Public Health Ontario (PHO) publishes various infectious disease surveillance reports, but none have yet been formally evaluated. OBJECTIVE: PHO evaluated its monthly and annual infectious disease surveillance reports to assess public health stakeholders' current perception of the products and to develop recommendations for improving future products. DESIGN: An evaluation consisting of an online survey and a review of public Web sites of other jurisdictions with similar annual reports. SETTING: For the online survey, stakeholder organizations targeted were the 36 local public health units and the Health health ministry in Ontario, Canada. PARTICIPANTS: Survey participants included epidemiologists, managers, directors, and other public health practitioners from participating organizations. MAIN OUTCOME MEASURES: Online survey respondents' awareness and access to the reports, their rated usefulness of reports and subsections, and suggestions for improving usefulness; timeliness of select annual reports from other jurisdictions based on the period from data described to report publication. RESULTS: Among 57 survey respondents, between 74% and 97% rated each report as useful; the most common use was for situational awareness. Respondents ranked timeliness as the most important attribute of surveillance reports, followed by data completeness. Among 6 annual reports reviewed, the median time to publication was 11.5 months compared with 23.2 months for PHO. CONCLUSION: Recommendations based on this evaluation have already been applied to the monthly report (eg, focusing on the most useful sections) and have become key considerations when developing future annual reports and other surveillance reporting tools (eg, need to provide more timely reports). Other public health organizations may also use this evaluation to inform aspects of their surveillance report development and evaluation. The evaluation results have provided PHO with direction on how to improve its provincial infectious disease surveillance reporting moving forward, and formed a basis for future work in surveillance product development and evaluation.

Systems Addressing Frail Elder Care: Description of a Successful Model.

OBJECTIVE: The aim of this article is to describe the Systems Addressing Frail Elder (SAFE) Care model, features of the interprofessional team and reengineered workflow, and details of the intervention. BACKGROUND: Older inpatients are vulnerable to adverse events related to frailty. SAFE Care, an interprofessional team-based program, was developed and evaluated in a cluster randomized controlled trial (C-RCT). Results found reduced length of stay and complications. The purpose of this article is to support and encourage the replication of this innovation or to help facilitate implementation of a similar process of organizational change. METHODS: This was a review of model features and intervention data abstracted from electronic health records. RESULTS: Salient features of team composition, training, and workflow are presented. The C-RCT intention-to-treat sample included 792 patients, of whom 307 received the SAFE Care huddle intervention. The most frequent problem was mobility (85.7%), and most frequent recommendation was fall precautions protocol (83.1%). CONCLUSIONS: The SAFE Care model may provide a standardized framework to approach, assess, and address the risks of hospitalized older adults.

Vitamin D Supplementation Does Not Affect Metabolic Changes Seen With ART Initiation.

BACKGROUND: Insulin resistance and lipid changes are common after antiretroviral therapy (ART) initiation. Observational studies suggest that vitamin D supplementation reduces the risk of developing diabetes and improves lipid profiles. METHODS: This 48-week prospective, randomized, double-blind, placebo-controlled study evaluated high-dose vitamin D3 (4000 IU daily) plus calcium supplementation (1000 mg calcium carbonate daily) in HIV-infected participants initiating ART with efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF). Changes in insulin resistance (as estimated by homeostatic model assessment), fasting lipid profile, and components of the metabolic syndrome were assessed at baseline, 24 weeks, and 48 weeks. Stratified Wilcoxon rank sum tests and stratified normal score tests were used to evaluate differences between treatment arms, stratified by screening 25-OH vitamin D stratum (≤/>20 ng/mL). RESULTS: A total of 165 participants enrolled: 79 in the vitamin D/calcium (Vit D/Cal) arm and 86 in the placebo arm. Only the placebo arm experienced a modest increase in insulin resistance at week 24 (P < .001). While increases in total and high-density lipoprotein cholesterol were significant in both arms at weeks 24 and 48, increases in low-density lipoprotein cholesterol at week 24 were only identified in the placebo arm (P = .011). Body mass index remained stable, whereas modest increases in waist circumference were observed in the placebo arm. Metabolic syndrome was present in 19 participants (12%) at baseline and 20 participants (14%) at week 48, without differences between arms. CONCLUSIONS: Vit D/Cal supplementation over 48 weeks did not alter the lipid profile or glucose metabolism experienced with initiation of EFV/FTC/TDF in ART-naïve persons. Vitamin D supplementation is unlikely to be an effective strategy to attenuate metabolic dysregulations with ART initiation.

Racial differences in calculated bioavailable vitamin D with vitamin D/calcium supplementation.

OBJECTIVES: Some studies suggest that bioavailable 25-dihydroxyvitamin D [25-(OH)D] is more accurate than total 25-(OH)D as an assessment of vitamin D (VitD) status in black individuals. We hypothesized that increases in bioavailable 25-(OH)D would correlate better with improvement in bone outcomes among black HIV-infected adults. DESIGN: This is a secondary analysis of AIDS Clinical Trials Group A5280, a randomized, double-blind study of VitD3 and calcium supplementation in HIV-infected participants initiating antiretroviral therapy. METHODS: Effect of VitD/calcium on total and calculated bioavailable 25-(OH)D, parathyroid hormone, bone turnover markers, and bone mineral density in black and nonblack participants were evaluated at 48 weeks. Wilcoxon signed-rank tests and Wilcoxon rank sum tests assessed within and between-race differences. RESULTS: Of 165 participants enrolled, 129 (40 black and 89 nonblack) had complete data. At baseline, black participants had lower total 25-(OH)D [median (Q1,Q3) 22.6 (15.8, 26.9) vs. 31.1 (23.1, 38.8) ng/ml, P < 0.001] but higher bioavailable 25-(OH)D [2.9 (1.5, 5.2) vs. 2.0 (1.5, 3.0) ng/ml, P = 0.022] than nonblack participants. After 48 weeks of VitD/calcium supplementation, bioavailable 25-(OH)D increased more in black than nonblack participants, but there were no between-race differences change in bone turnover markers or bone mineral density. The associations between increases in 25-(OH)D levels and change in bone outcomes appeared similar for both total and bioavailable 25-(OH)D. CONCLUSION: Baseline and change in bioavailable 25-(OH)D were higher among black adults initiating antiretroviral therapy with VitD/calcium; however, associations between 25-(OH)D and bone outcomes appeared similar for total and bioavailable 25-(OH)D. The assessment of total 25-(OH)D may be sufficient for evaluation of VitD status in black HIV-infected individuals. TRIAL REGISTRATION NUMBER: NCT01403051.

Effects of atorvastatin on biomarkers of immune activation, inflammation, and lipids in virologically suppressed, human immunodeficiency virus-1-infected individuals with low-density lipoprotein cholesterol <130 mg/dL (AIDS Clinical Trials Group Study A5275).

BACKGROUND: Persistent immune activation and inflammation in virologically suppressed human immunodeficiency virus (HIV) infection are linked to excess cardiovascular risk. OBJECTIVE: To evaluate atorvastatin as a strategy to reduce cardiovascular risk. METHODS: A5275 was a multicenter, prospective, randomized, double-blind, placebo-controlled, cross-over pilot study of atorvastatin (10 mg/day for 4 weeks then 20 mg/day for 16 weeks) with a planned enrollment of 97 HIV-infected participants ≥18 years old, receiving boosted protease inhibitor-based antiretroviral therapy for ≥6 months, with plasma HIV-1 RNAs below limits of quantification ≥180 days, and fasting low-density lipoprotein (LDL) cholesterol ≥70 and <130 mg/dL. Primary endpoints were differences of changes ([week 44-week 24]-[week 20-baseline]) in CD4+ and CD8+ T-lymphocyte activation (% CD38+/DR+) and plasma levels of IL-6 and D-dimer. Arms were compared using the Wilcoxon rank-sum tests and also summarized changes pre-to-post atorvastatin treatment. Analyses were as-treated. RESULTS: Ninety-eight participants were enrolled at 31 U S sites and 73 completed study treatment. Atorvastatin treatment did not decrease T-lymphocyte or monocyte activation, circulating biomarker levels (interleukin-6, D-dimer, soluble CD14, soluble CD163, monocyte chemoattractant protein-1, interferon-gamma-induced protein-10, high-sensitivity C-reactive protein, CD40L, and P-selectin) or white blood cell Krüppel-like Factor 2/4 messenger RNA levels. Pre-to-post atorvastatin reductions in calculated LDL (-38%), oxidized-LDL (-33%), and lipoprotein-associated phospholipase A2 (-31%) were significant (P < .01). CONCLUSION: In virologically suppressed individuals with HIV infection, atorvastatin did not significantly decrease levels of soluble or cellular biomarkers of immune activation and inflammation but resulted in robust reductions in LDL cholesterol, oxLDL, and lipoprotein-associated phospholipase A2, biomarkers associated with cardiovascular risk.

Neurocognition with maraviroc compared with tenofovir in HIV.

OBJECTIVE: The objective was to determine whether maraviroc (MVC) has unique neurocognitive benefits in the context of initial antiretroviral therapy (ART). DESIGN: Randomized, double-blind, placebo-controlled, 48-week trial. SETTING: Participants were enrolled in US AIDS Clinical Trials Group clinical trial sites. PARTICIPANTS: Total 262 ART-naive, chemokine coreceptor 5 tropic HIV, and HIV RNA greater than 1000 copies/ml participants were randomized, 230 participants completed the study. INTERVENTION: Participants received MVC 150 mg or tenofovir disoproxil fumarate (TDF) 300 mg on a background of ritonavir-boosted darunavir and emtricitabine. MAIN OUTCOME MEASURE(S): The neuropsychological battery of 15 tests done at baseline, week 24 and week 48 assessed seven domains, and were standardized into z-scores then converted into deficit scores and a global deficit score. The 48-week changes from baseline in the neuropsychological scores and the global deficit score were compared by Wilcoxon or Kruskal-Wallis test between arms, and among baseline impairment groups [classified as normal, mild (2 deficit scores ≥1) and moderate (2 deficit scores ≥2)]. It was hypothesized that the MVC arm would have improved neuropsychological performance over TDF. RESULTS: In this double-blind, randomized, placebo-controlled trial, there were no differences in neuropsychological performance between MVC and TDF. Those with moderate neuropsychological impairment at baseline experienced greater ART-mediated neuropsychological improvement than those with mild or no neuropsychological impairment. CONCLUSION: Improvement in neurocognitive functioning was greater with more baseline impairment but was comparable with MVC or TDF.

Differential CD4+ cell count increase and CD4+ :  CD8+ ratio normalization with maraviroc compared with tenofovir.

OBJECTIVE: Studies exploring the immunologic effects of maraviroc (MVC) have produced mixed results; hence, it remains unclear whether MVC has unique immunologic effects in comparison with other antiretroviral drugs. We sought to determine whether MVC has differential effects compared with tenofovir disoproxil fumarate (TDF) during initial antiretroviral therapy. DESIGN: Prospective study in AIDS Clinical Trials Group A5303, a double-blind, placebo-controlled trial (N = 262) of MVC vs. TDF, each combined with boosted darunavir and emtricitabine. METHODS: A total of 31 cellular and soluble biomarkers were assayed at weeks 0 and 48. Polychromatic flow cytometry was performed on cryopreserved peripheral blood mononuclear cells. Soluble markers were assayed in plasma using ELISA kits. Analyses were as treated. RESULTS: Analyses included 230 participants (119 in MVC arm and 111 in TDF arm). Over 48 weeks of treatment, no significant differences were detected in declines in markers of inflammation and activation with MVC vs. TDF. A greater CD4 T-cell count increase (median +234 vs. +188 cells/µl, P = 0.036), a smaller CD8 T-cell count decrease (-6 vs. -109 cells/µl, P = 0.008), and a smaller CD4 : CD8 ratio increase (0.26 vs. 0.39, P = 0.003) occurred with MVC. Among participants with a baseline CD4 : CD8 ratio less than 1, a smaller proportion of MVC group normalized to a ratio greater than 1 at week 48 (15 and 36%, P < 0.001). CONCLUSION: MVC resulted in less improvement in the CD4 : CD8 ratio driven by greater increase in CD4 cell count but smaller decline in CD8 cell count. Changes in soluble or cellular biomarkers of inflammation and immune activation were not different between MVC and TDF.

Identification and team-based interprofessional management of hospitalized vulnerable older adults.

BACKGROUND: Extended hospital stays and complications are common among older adults and may lead to morbidity and loss of independence. Specialized geriatric units have been shown to improve outcomes but, with the growing numbers of older adults, may be difficult to scale to meet needs. PURPOSE: The purpose was to evaluate a quality improvement initiative that redesigned unit-based workflow and trained interprofessional teams on general medical/surgical units to create care plans for vulnerable older adults using principles of comprehensive geriatric assessment and team management. METHOD: The evaluation included a cluster randomized controlled trial of 10 medical/surgical units and intention-to-treat analysis of all patients meeting risk screening criteria. RESULTS: N = 1,384, median age = 80.9 years, and 53.5% female. Mean difference in observed vs. expected length of stay was 1.03 days shorter (p = .006); incidence of complications (odds ratio [OR] = 0.45; 95% confidence interval [CI] = 0.21-0.98) and transfer to intensive care (OR = 0.45; 95% CI = 0.25-0.79) lower among patients admitted to intervention units; incidence of discharge to institutional care was higher (OR = 1.43; 95% CI = 1.06-1.93). Mortality during hospitalization (OR = 0.64; 95% CI = 0.37-1.11) did not differ between groups. CONCLUSION: Reorganizing general medical/surgical units to provide team-based interprofessional care can improve outcomes among hospitalized older adults.

Vitamin D and Calcium Attenuate Bone Loss With Antiretroviral Therapy Initiation: A Randomized Trial.

BACKGROUND: Antiretroviral therapy initiation for HIV-1 infection is associated with 2% to 6% loss of bone mineral density (BMD). OBJECTIVE: To evaluate the effect of vitamin D3 plus calcium supplementation on bone loss associated with antiretroviral therapy initiation. DESIGN: 48-week prospective, randomized, double-blind, placebo-controlled study. (ClinicalTrials.gov: NCT01403051). SETTING: 39 AIDS Clinical Trials Group units. PATIENTS: Adults with antiretroviral therapy-naive HIV. MEASUREMENTS: BMD by dual-energy x-ray absorptiometry, 25-hydroxyvitamin D levels, and other laboratory assessments. RESULTS: 165 eligible patients were randomly assigned (79 received vitamin D3 plus calcium and 86 received placebo). The study groups were well-balanced at baseline: 90% were men, 33% were non-Hispanic black, and the median CD4 count was 0.341 × 109 cells/L. At 48 weeks, the percentage of decline in total hip BMD was smaller in the vitamin D3 plus calcium group than in the placebo group: Medians were -1.36% (interquartile range [IQR], -3.43% to 0.50%) and -3.22% (IQR, -5.56% to -0.88%), respectively (P = 0.004). Similar results were seen at the lumbar spine. At 48 weeks, 90% of patients achieved HIV-1 RNA levels less than 50 copies/mL. Levels of 25-hydroxyvitamin D3 increased with vitamin D3 plus calcium but not with placebo: Median change was 61.2 nmol/L (IQR, 36.4 to 94.3) versus 1.7 nmol/L (IQR, -13.2 to 10.7) (P < 0.001). Overall, 103 patients (62%) reported 1 or more adverse event, with similar distribution between groups; no cases of hypercalcemia and 1 case of nephrolithiasis were reported in the placebo group. LIMITATION: No international sites were included, and follow-up was only 48 weeks. CONCLUSION: Vitamin D3 plus calcium supplementation mitigates the BMD loss seen with initiation of efavirenz/emtricitabine/tenofovir disoproxil fumarate.

Less Bone Loss With Maraviroc- Versus Tenofovir-Containing Antiretroviral Therapy in the AIDS Clinical Trials Group A5303 Study.

BACKGROUND: There is a need to prevent or minimize bone loss associated with antiretroviral treatment (ART) initiation. We compared maraviroc (MVC)- to tenofovir disoproxil fumarate (TDF)-containing ART. METHODS: This was a double-blind, placebo-controlled trial. ART-naive subjects with human immunodeficiency virus type 1 RNA load (viral load [VL]) >1000 copies/mL and R5 tropism were randomized to MVC 150 mg or TDF 300 mg once daily (1:1), stratified by VL <100 000 or ≥100 000 copies/mL and age <30 or ≥30 years. All subjects received darunavir 800 mg, ritonavir 100 mg, and emtricitabine 200 mg daily. Dual-energy X-ray absorptiometry scanning was done at baseline and week 48. The primary endpoint was percentage change in total hip bone mineral density (BMD) from baseline to week 48 in the as-treated population. RESULTS: We enrolled 262 subjects. A total of 259 subjects (130 MVC, 129 TDF) contributed to the analyses (91% male; median age, 33 years; 45% white, 30% black, 22% Hispanic). Baseline median VL was 4.5 log10 copies/mL and CD4 count was 390 cells/µL. The decline in hip BMD (n = 115 for MVC, n = 109 for TDF) at week 48 was less with MVC (median [Q1, Q3] of -1.51% [-2.93%, -0.11%] vs -2.40% [-4.30%, -1.32%] for TDF (P < .001). Lumbar spine BMD decline was also less with MVC (median -0.88% vs -2.35%; P < .001). Similar proportions of subjects in both arms achieved VL ≤50 copies/mL in as-treated and ITT analyses. CONCLUSIONS: MVC was associated with less bone loss at the hip and lumbar spine compared with TDF. MVC may be an option to attenuate ART-associated bone loss. CLINICAL TRIALS REGISTRATION: NCT01400412.

Rifaximin has a marginal impact on microbial translocation, T-cell activation and inflammation in HIV-positive immune non-responders to antiretroviral therapy - ACTG A5286.

BACKGROUND: Rifaximin, a nonabsorbable antibiotic that decreases lipopolysaccharide (LPS) in cirrhotics, may decrease the elevated levels of microbial translocation, T-cell activation and inflammation in human immunodeficiency virus (HIV)-positive immune nonresponders to antiretroviral therapy (ART). METHODS: HIV-positive adults receiving ART for ≥96 weeks with undetectable viremia for ≥48 weeks and CD4(+) T-cell counts <350 cells/mm(3) were randomized 2:1 to rifaximin versus no study treatment for 4 weeks. T-cell activation, LPS, and soluble CD14 were measured at baseline and at weeks 2, 4, and 8. Wilcoxon rank sum tests compared changes between arms. RESULTS: Compared with no study treatment (n = 22), rifaximin (n = 43) use was associated with a significant difference between study arms in the change from baseline to week 4 for CD8(+)T-cell activation (median change, 0.0% with rifaximin vs +0.6% with no treatment; P = .03). This difference was driven by an increase in the no-study-treatment arm because there was no significant change within the rifaximin arm. Similarly, although there were significant differences between study arms in change from baseline to week 2 for LPS and soluble CD14, there were no significant changes within the rifaximin arm. CONCLUSIONS: In immune nonresponders to ART, rifaximin minimally affected microbial translocation and CD8(+)T-cell activation. Trial registration number. NCT01466595.

Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207.

BACKGROUND: Intrapartum single-dose nevirapine (sdNVP) reduces HIV-1 perinatal transmission but selects NVP resistance among mothers and infants. We evaluated the frequency of antiretroviral resistance among infants with intrauterine HIV-1 infection exposed to sdNVP and maternal antenatal or breastfeeding antiretroviral therapy. METHODS: This analysis included 429 infants from sub-Saharan Africa, India and Haiti whose 422 mothers received sdNVP plus maternal study treatment. At entry mothers had CD4>250/µL and were ART-naïve except for antenatal ZDV per local standard of care. Maternal study treatment started intrapartum and included ZDV/3TC, TDF/FTC or LPV/r for 7 or 21 days in a randomized factorial design. Infants received sdNVP study treatment and ZDV if local standard of care. Infant HIV RNA or DNA PCR and samples for genotype were obtained at birth and weeks 2, 4 and 12; infants who ever breast-fed were also tested at weeks 16, 24, 48 and 96. Samples from HIV-1-infected infants were tested for drug resistance by population genotype (ViroSeq). NVP or NRTI resistance mutations were assessed using the IAS-USA mutation list. RESULTS: Perinatal HIV-1 transmission occurred in 17 (4.0%) infants including 12 intrauterine infections. Resistance mutations were detected among 5 (42%) intrauterine-infected infants; of these, 3 had mutations conferring resistance to NVP alone, 1 had resistance to NRTI alone, and 1 had dual-class resistance mutations. Among the 2 infants with NRTI mutations, one (K70R) was likely maternally transmitted and one (K65R) occurred in the context of breastfeeding exposure to maternal antiretroviral therapy. CONCLUSIONS: Infants with intrauterine HIV infection are at risk of acquiring resistance mutations from exposure to maternal antiretroviral medications intrapartum and/or during breastfeeding. New approaches are needed to lower the risk of antiretroviral resistance in these infants.

Dynamics of immune reconstitution and activation markers in HIV+ treatment-naïve patients treated with raltegravir, tenofovir disoproxil fumarate and emtricitabine.

BACKGROUND: The dynamics of CD4+ T cell reconstitution and changes in immune activation and inflammation in HIV-1 disease following initiation of antiretroviral therapy (ART) are incompletely defined and their underlying mechanisms poorly understood. METHODS: Thirty-nine treatment-naïve patients were treated with raltegravir, tenofovir DF and emtricitabine. Immunologic and inflammatory indices were examined in persons with sustained virologic control during 48 weeks of therapy. RESULTS: Initiation of ART increased CD4+ T cell numbers and decreased activation and cell cycle entry among CD4+ and CD8+ T cell subsets, and attenuated markers of coagulation (D-dimer levels) and inflammation (IL-6 and TNFr1). These indices decayed at different rates and almost all remained elevated above levels measured in HIV-seronegatives through 48 weeks of viral control. Greater first and second phase CD4+ T cell restoration was related to lower T cell activation and cell cycling at baseline, to their decay with treatment, and to baseline levels of selected inflammatory indices, but less so to their changes on therapy. CONCLUSIONS: ART initiation results in dynamic changes in viral replication, T cell restoration, and indices of immune activation, inflammation, and coagulation. These findings suggest that determinants of T cell activation/cycling and inflammation/coagulation may have distinguishable impact on immune homeostasis. TRIAL REGISTRATION: Clinicaltrials.gov NCT00660972.

Analysis of females with Chlamydia trachomatis infections attending a sexually transmissible infection clinic in Singapore in 2010.

BACKGROUND: Chlamydia (Chlamydia trachomatis) is the most commonly diagnosed sexually transmissible infection (STI) in Singapore, with rising incidence. METHOD: Random sampling was performed on all chlamydia-positive samples collected from female patients who attended a women's clinic from January 2010 to December 2010. Some 250 electronic medical records were analysed. Population demographics, sexual histories, symptoms, diagnostic methods and management were recorded. RESULTS: One hundred and forty-two (56.8%) patients were under 25 years of age. The predominant race diagnosed with Chlamydia cervicitis were Chinese (116 cases, 46.4%) followed by 86 (34.4%) Malays and 20 (8%) Filipinos. Sixty-three (25.2%) were skilled workers and (47) 18.8% were students. Professionals and office workers together formed 68 (27.2%) of the patients. Some 248 (99.2%) patients were heterosexual and 2 (0.8%) patients were bisexual; 229 (91.6%) patients had regular partners, 18 (7.2%) had casual partners and 3 (1.2%) had both. Concurrency prevalence accounted for 49 cases (19.6%) and condom use was less common. Patients were generally asymptomatic, with 114 (45.5%) presenting with symptoms. One hundred and eight (43.2%) patients had 2-5 sexual partners in their lifetime. Patients with a termination made up 12% of our cohort. This episode of infection was the first diagnosis of an STI for 198 (79.2%) patients; 24 (9.6%) of patients had been previously diagnosed with chlamydia. CONCLUSION: Chlamydia infection was most prevalent in skilled workers and their regular partners with heterosexual practices under 25 years old. Most patients had 2-5 sexual partners and did not use condoms consistently or at all.

Development and maintenance of a controlled vocabulary via an electronic collaborative platform.

The development of electronic health records and clinical information systems has been progressing at a quickened pace in recent years. With such change, the use of standard vocabulary has aroused much interest. However, classification code sets are developed for their distinctive purposes, no single vocabulary set could satisfy the needs of all specialties; moreover, local customization would be inevitable. This poster describes how a controlled vocabulary with contribution from frontline clinicians was set up in Hong Kong Hospital Authority (HA). The adoption of an electronic maintenance portal with collaboration of representatives from all institutions would also be discussed. The use of such table has helped to maintain the interoperability of captured data between departments, specialties and institutions.

Higher expression of several interferon-stimulated genes in HIV-1-infected females after adjusting for the level of viral replication.

BACKGROUND: Clinical studies have shown faster disease progression and stronger immune activation in human immunodeficiency virus (HIV)-1-infected females when compared with males for the same level of HIV-1 replication. Here we determine whether the elevated levels of HIV-1-induced interferon-alpha (IFN-α) production observed in females are associated with higher interferon-stimulated gene (ISG) expression levels in T cells, hence suggesting type-I IFN as a mechanism for the higher HIV-1-associated immune activation observed. METHODS: T-cell and dendritic cell populations were isolated from treatment-naive chronically HIV-1-infected individuals enrolled in the Adult Clinical Trials Group 384 by fluorescence-activated cell sorting. The expression of 98 genes involved in Toll-like receptor and type I IFN signaling pathways were quantified using Nanostring technology. RESULTS: Several ISGs were significantly correlated with HIV-1 viral load and/or CD4(+) T-cell count. Higher expression levels of a subset of these ISGs were observed in cells derived from females as compared to males after adjusting for viral load and were correlated to higher levels of T-cell activation. CONCLUSION: These data show that higher IFN-α production is associated with higher ex vivo expression of several ISGs in females. This might contribute to higher levels of immune activation and the observed faster HIV-1 disease progression in females for a given level of viral replication.