Who Is at Risk for New Hepatitis B Infections Among People With HIV?

Hepatitis B virus (HBV) increases morbidity and mortality among people with HIV (PWH). We retrospectively analyzed HBV incidence among 5785 PWH. Fourteen had newly positive hepatitis B s antigen (mean 5.2 person-years of follow-up, 46.4/100 000 infections/year). These data show gaps in HBV vaccination and in the preventative efficacy of HBV-specific antiretroviral therapy.

Persistent low prevalence of hepatitis B vaccination among people with HIV: Time for a change?

Hepatitis B virus (HBV) infection is one of the leading causes of hepatocellular carcinoma and mortality among people living with HIV (PLWH). HBV vaccination provides protection from infection; however, vaccination rates are low. We conducted a retrospective analysis at three HIV centres in Texas to determine the proportion of PLWH who received the recommended 3 doses of hepatitis B vaccine within 1 year. Factors associated with vaccination completion were explored. In our sample of three sites in a state with high HIV transmission and high rates of liver disease from 2011 to 2021, showed low rates of hepatitis B vaccination. Among eligible PLWH, only 9% completed the 3-dose hepatitis B vaccine series in 1 year. There is an urgent need to improve HBV vaccination to reach 2030 target for hepatitis B elimination.

Incidence and Predictors of Hepatitis B Surface Antigen Clearance in HIV Patients: A Retrospective Multisite Study.

BACKGROUND: New therapies to achieve hepatitis B surface antigen (HBsAg) clearance are under development. However, gaps in knowledge exist in understanding the incidence and predictors of HBsAg clearance in a racially diverse HIV population. METHODS: We examined the incidence and risk of HBsAg clearance in a retrospective cohort of people with HIV/hepatitis B virus (HBV). Included patients had sufficient data to establish chronic infection based on Centers for Disease Control and Prevention guidelines. We examined the incident rate for HBsAg loss and hazard rate ratios to evaluate predictors for HBsAg clearance in a multivariable model. RESULTS: Among 571 HIV/HBV patients, 87% were male, 61% were Black, 45% had AIDS, 48% were HBeAg positive, and the median follow-up was 88 months. Incident HBsAg clearance was 1.5 per 100 person-years. In the multivariate model, those with AIDS at baseline (adjusted hazard ratio [aHR], 2.43; 95% CI, 1.37-4.32), Hispanics (aHR, 3.57; 95% CI, 1.33-9.58), and those with injection drug use as an HIV risk factor (aHR, 3.35; 95% CI, 1.26-8.89) were more likely to lose HBsAg, whereas those who were HBeAg positive (aHR, 0.34; 95% CI, 0.19-0.63) were less likely to lose HBsAg. The median change in CD4 cell count during the observation period was 231 cells/mm3 in those with HBsAg loss vs 112 cells/mm3 in those with HBsAg persistence (P = .004). CONCLUSIONS: HBsAg loss occurs in about 10% of those with chronic HBV infection. Being Hispanic, having AIDS at baseline, having an injection drug use history, and having HBeAg-negative status at baseline predicted the likelihood of HBsAg loss. Immune restoration may be a mechanism through which HBsAg loss occurs in HIV patients.

HIV Testing in Adults Presenting With Central Nervous System Infections.

BACKGROUND: Universal HIV testing in adults presenting to a health care setting was recommended by the Centers for Disease Control and Prevention (CDC) in 2006, but compliance in central nervous system (CNS) infections is unknown. METHODS: A multicenter study of adults presenting with CNS infections to 18 hospitals in Houston and New Orleans between 2000 and 2015 was done to characterize HIV testing and explore factors associated with a positive HIV test. RESULTS: A total of 1478 patients with a diagnosis of meningitis or encephalitis were identified; 180 were excluded because of known HIV diagnosis (n = 100) or were <17 years old (n = 80). Out of 1292 patients, 642 (49.7%) had HIV testing, and testing did not differ significantly before or after the CDC recommendations in 2006 (53% vs 48%; P = .068). An HIV test was more commonly done in patients who were non-Caucasian, had fever >38°C, or had seizures on presentation, and of those tested, non-Caucasian patients and those with photophobia were more likely to have a positive HIV test (P < .05). HIV testing also varied by type of CNS infection: community-acquired bacterial meningitis (98/130, 75.4%), encephalitis (174/255, 68.2%), aseptic meningitis (285/619, 46.0%), and health care-associated meningitis (85/288, 29.5%; P < .001). CONCLUSIONS: Even though HIV testing should be done in all adults presenting with a CNS infection, testing remains ~50% and did not improve after the recommendation for universal testing by the CDC in 2006.

Evaluation of Six Weekly Oral Fecal Microbiota Transplants in People with HIV.

BACKGROUND: Reduced microbiota diversity (dysbiosis) in people with HIV (PWH) likely contributes to inflammation, a driver of morbidity and mortality. We aimed to evaluate the safety and tolerability of 6 weekly oral fecal microbiota transplants (FMT) administered to reverse this dysbiosis. METHODS: Six PWH on suppressive antiretroviral therapy (ART) received 6 weekly doses of lyophilized fecal microbiota product from healthy donors. Shotgun sequencing on stool before, after last FMT, and 20 weeks thereafter was performed. Inflammation and gut permeability biomarkers were measured. RESULTS: Median age at week 0 was 39 years, CD4+ T cell count 496 cells/mm3, HIV RNA levels <20 copies/mL. FMT was safe and well-tolerated. α diversity increased in 4 participants from weeks 0 to 6, including the 3 with the lowest α diversity at week 0. At week 26, α diversity more closely resembled week 0 than week 6 in these 4 participants. Metagenomic analysis showed no consistent changes across all participants. One participant had high gut permeability and inflammation biomarker levels and low α diversity that improved between weeks 0 and 6 with a shift in distribution. CONCLUSIONS: Weekly FMT was safe and well-tolerated. α diversity increased in participants with the lowest baseline α diversity during the treatment period. Future randomized, controlled trials of FMT should consider evaluating PWH with greater inflammation, gut damage, or dysbiosis as this population may be most likely to show a significant response.ClinicalTrials.gov Identifier: NCT03329560.

Timing of Antiretroviral Therapy Initiation Determines Rectal Natural Killer Cell Populations.

Despite antiretroviral therapy (ART), innate and adaptive immunologic damage persists in the periphery and gut. T memory stem cells (Tscm) and natural killer (NK) cells are pivotal for host defense. Tscm are memory cells capable of antigen response and self-renewal, and circulating and gut NK cell populations may facilitate HIV control. The impact of early ART on circulating and gut Tscm and NK cells is unknown. We enrolled participants who initiated ART during acute versus chronic HIV-1 infection versus no ART in chronic infection. We performed flow cytometry to identify NK and Tscm cells in the blood and rectum and polymerase chain reaction to quantify the HIV-1 reservoir in both sites. We used the Mann-Whitney U-test and Spearman correlation coefficients for analysis. Participants who started ART in acute infection had lower rectal CD56brightCD16dim cell frequencies than participants who started ART in chronic HIV-1 infection and lower CD56bright and CD56brightCD16- cell frequencies than participants with chronic infection without ART. Higher circulating NK cell, CD56-CD16bright, CD56dim, and CD56dimCD16bright frequencies correlated with higher HIV-1 DNA levels in rectal CD4+ T cells, whereas higher circulating CD4+ T cell counts correlated with higher rectal NK, CD56brightCD16dim, and CD56dimCD16bright frequencies. Peripheral CD56brightCD16- cells were inversely associated with rectal CD56-CD16bright cells. Rectal CD8+ Tscm frequencies were higher in participants without ART than participants with chronic infection on ART. Timing of ART initiation determines rectal NK cell populations, and ART may influence rectal Tscm populations. Whether the gut reservoir contributes to NK cell activation requires further study.

Seroprevalence of Strongyloides stercoralis and Evaluation of Universal Screening in Kidney Transplant Candidates: A Single-Center Experience in Houston (2012-2017).

BACKGROUND: Disseminated strongyloidiasis in solid organ transplant recipients is a rare but devastating infection. In our center, we implemented a universal screening of all candidates for kidney transplantation. We assessed the seroprevalence and utility of universal screening for strongyloidiasis in our center. METHODS: Patients were identified from our transplant referral list (from July 2012 to June 2017). Demographics, pretransplant laboratory, and serological screenings were retrospectively collected. For Strongyloides-seropositive (SSp) patients, data on travel history, symptoms, treatment, and stool ova and parasite examinations were extracted. Logistic regression and multiple imputation for missing data were performed. RESULTS: A total of 1689 patients underwent serological screening, of whom 168 (9.9%) were SSp. Univariate analysis revealed that SSp patients had higher rates of eosinophilia, diabetes mellitus, latent tuberculosis and were likely to be either Hispanic or Asian (P < .05). In multivariate analysis, eosinophilia (P = .01), diabetes mellitus (P = .02), and Asian race (P = .03) were associated with being SSp, but 45 (27%) of the SSp patients did not have any of these 3 factors, and 18 SSp patients (11%) had no epidemiological risk factors. All patients received ivermectin, and none developed disseminated strongyloidiasis. Of patients who underwent serological screening on multiple occasions, 6.8% seroconverted while waiting for kidney transplantation. CONCLUSIONS: We found a high rate of Strongyloides seropositivity among our kidney transplantation candidates. No epidemiological risk factors effectively predicted SSp status in our population, and universal screening identified a large number of patients without such factors. Serial screening should be considered when a long wait time is expected before transplantation.

Sources of clinical information used in HIV care and treatment: Are providers' choices related to their demographic and practice characteristics?

HIV medical care providers need a wide range of evidence-based clinical information resources to manage their patients' health. We determined whether providers' choice of information sources for HIV care and treatment are associated with their demographic and medical practice characteristics. Data used for this study were obtained from a probability sample of HIV medical care providers in 13 outpatient HIV facilities in Houston/Harris County, Texas, surveyed between June and September 2009. The mean number of information sources used by HIV medical care providers for HIV care and treatment was 5.83 (95% confidence interval: 4.90-6.75). Antiretroviral therapy guidelines (95.6%), medical journals and textbooks (82.6%), and Internet sources (69.5%) were ranked first, second, and third as sources of clinical information. At least one of the providers' demographic or medical practice characteristics was significantly (p ⩽ 0.05) associated with six of the clinical information sources. Integration of these information resources into clinicians' workflow may enhance efficiency of HIV care and treatment and facilitate improved patients' care and health outcomes.

Outpatient Infection Prevention: A Practical Primer.

As more patients seek care in the outpatient setting, the opportunities for health care-acquired infections and associated outbreaks will increase. Without uptake of core infection prevention and control strategies through formal initiation of infection prevention programs, outbreaks and patient safety issues will surface. This review provides a step-wise approach for implementing an outpatient infection control program, highlighting some of the common pitfalls and high-priority areas.

Community-Acquired Meningitis in HIV-Infected Patients in the United States.

We conducted a retrospective study of 549 adults admitted with community-acquired meningitis (CAM) to several hospitals in New Orleans, LA and Houston, TX between 1999 and 2014 to characterize the current epidemiology, clinical manifestations, cerebrospinal fluid (CSF) characteristics, and outcomes of CAM between HIV-infected and uninfected patients and to identify risk factors for adverse outcomes in CAM. Bivariate analysis and logistic regression analysis were used to identify prognostic factors. A total of 1022 patients with CAM were screened. Only 549 (53.7%) subjects had an HIV test and were included in the study. Of those, 138 (25%) had HIV infection. HIV-infected patients presented with less meningeal symptoms (headache, neck stiffness, and Kernig sign), but with higher rates of hypoglycorrhachia, elevated CSF protein, and an abnormal cranial imaging (p < 0.05). More than 50% of all the patients had an unknown etiology. Cryptococcal meningitis was the most common identified etiology of CAM in HIV-infected patients followed by neurosyphilis and varicella-zoster virus (VZV). Viral and bacterial etiologies were the most frequent etiologies in non-HIV-infected patients. Streptococcus pneumoniae was the most common bacterial pathogen in both groups, but it was rare overall (2%). Adverse clinical outcomes were similar in both groups (27% vs. 24%). Logistic regression identified hypoglycorrhachia and an abnormal neurological examination as independent predictor factors of worse outcome in all patients with meningitis. Our results demonstrate that the etiology, clinical presentation, and CSF findings differ between HIV-infected and HIV-uninfected adults with CAM, but clinical outcomes are similar.

Carbapenem-resistant Lactobacillus intra-abdominal infection in a renal transplant recipient with a history of probiotic consumption.

BACKGROUND: Lactobacillus sp. is a low virulence bacterium, which rarely causes infection in immunocompetent individuals and usually is considered a contaminant. Normally this organism is susceptible to ß-lactam antibiotics, yet resistant strains have been reported. CASE PRESENTATION AND DISCUSSION: Here, we report a case of a 60-year-old renal transplant recipient who developed an intra-abdominal abscess which grew a carbapenem-resistant Lactobacillus casei. This is significant since it is the first report of a clinical isolate of Lactobacillus sp. that demonstrated both microbiological and clinical resistance to carbapenem use. Moreover, the probiotic supplement that the patient had taken also grew a similar organism raising the concern of probiotic associated infection in immunocompromised individual.

A multicenter study of pandemic influenza A (H1N1) infection in patients with solid tumors in 3 countries: early therapy improves outcomes.

BACKGROUND: Pandemic influenza A (hereafter 2009/H1N1) caused significant morbidity and mortality during the 2009 pandemia. Patients with chronic medical conditions and immunosuppressive diseases had a greater risk of complications. However, data regarding the characteristics and outcome of 2009/H1N1 infection in patients with solid tumors are nonexistent. Herein, the authors describe a series of influenza 2009/H1N1 in patients with solid malignancies at 3 major cancer hospitals worldwide. METHODS: The authors retrospectively reviewed the records of patients with solid organ malignancies and 2009/H1N1 from The University of Texas M. D. Anderson Cancer Center in Houston, Texas; the Mexican National Cancer Institute, Federal District of Mexico; and King Hussein Cancer Center in Amman, Jordan from the period of the 2009 H1N1 pandemia. Data on demographics, disease characteristics, and outcome were extracted. RESULTS: In total, 115 cases were identified during the pandemic influenza among the 3 institutions. High rates of hospitalization (50%), pneumonia (23%), and death (9.5%) were reported. Patients who developed pneumonia and those who died were moderately to severely immunocompromised (P = .001 and P = .006, respectively). A multivariate competing risk analysis demonstrated that a delay >48 hours in starting antiviral therapy was associated significantly with an increased risk of developing pneumonia (P = .013). CONCLUSIONS: The 2009/H1N1 pandemic caused severe illness in immunocompromised patients with cancer who had solid tumors, and heavily immunosuppressed patients were at greater risk of developing pneumonia and death. Early initiation of antiviral therapy is crucial in this patient population to decrease morbidity and probably mortality.

Absence of XMRV in peripheral blood mononuclear cells of ARV-treatment naïve HIV-1 infected and HIV-1/HCV coinfected individuals and blood donors.

BACKGROUND: Xenotropic murine leukemia virus-related virus (XMRV) has been found in the prostatic tissue of prostate cancer patients and in the blood of chronic fatigue syndrome patients. However, numerous studies have found little to no trace of XMRV in different human cohorts. Based on evidence suggesting common transmission routes between XMRV and HIV-1, HIV-1 infected individuals may represent a high-risk group for XMRV infection and spread. METHODOLOGY/PRINCIPAL FINDINGS: DNA was isolated from the peripheral blood mononuclear cells (PBMCs) of 179 HIV-1 infected treatment naïve patients, 86 of which were coinfected with HCV, and 54 healthy blood donors. DNA was screened for XMRV provirus with two sensitive, published PCR assays targeting XMRV gag and env and one sensitive, published nested PCR assay targeting env. Detection of XMRV was confirmed by DNA sequencing. One of the 179 HIV-1 infected patients tested positive for gag by non-nested PCR whereas the two other assays did not detect XMRV in any specimen. All healthy blood donors were negative for XMRV proviral sequences. Sera from 23 HIV-1 infected patients (15 HCV(+)) and 12 healthy donors were screened for the presence of XMRV-reactive antibodies by Western blot. Thirteen sera (57%) from HIV-1(+) patients and 6 sera (50%) from healthy donors showed reactivity to XMRV-infected cell lysate. CONCLUSIONS/SIGNIFICANCE: The virtual absence of XMRV in PBMCs suggests that XMRV is not associated with HIV-1 infected or HIV-1/HCV coinfected patients, or blood donors. Although we noted isolated incidents of serum reactivity to XMRV, we are unable to verify the antibodies as XMRV specific.

Characteristics and outcomes of pandemic 2009/H1N1 versus seasonal influenza in children with cancer.

BACKGROUND: Novel 2009/H1N1 influenza has significant impact on immunocompromised children with cancer; however, it is uncertain how it compares with seasonal influenza (SFlu) in this vulnerable population. We compared clinical characteristics and outcomes for these 2 infections in children with cancer and identified risk factors for progression to lower respiratory infection (LRI) and/or death. METHODS: Influenza infections confirmed by positive viral culture and/or fluorescence antigen test between January 1998 and February 2010 were identified from microbiology databases at a comprehensive cancer center. Characteristics and outcomes were compared for the 2 groups. Kaplan-Meier survival curves and Cox proportional hazards model were generated to identify risk factors for LRI and/or death. RESULTS: When compared with SFlu, 2009/H1N1 cases had significantly lower acute physiology and chronic health evaluation II score (median: 9 versus 14), fewer comorbidities (15% versus 46%), fewer hematopoietic stem-cell transplantation (5% versus 16%), more solid tumors (45% versus 16%), higher LRI at presentation (20% versus 4%), higher rates of antiviral therapy (90% versus 48%) and higher mortality (10% versus 0%). Male gender (hazard ratio [HR]: 8.4, 95% confidence interval [CI]: 1.08-65.2, P = 0.042), acute physiology and chronic health evaluation II score > 15 (HR: 3.29, 95% CI: 1.04-10.39, P = 0.027) and a 24-hour delay in initiation of antiviral treatment (HR: 1.12, 95% CI: 1.02-1.23, P = 0.015) were the most significant predictors of progression to LRI and mortality, regardless of virus strain. CONCLUSIONS: Significant differences between 2009/H1N1 and SFlu with respect to clinical presentation, management and associated outcomes were identified. Early diagnosis and prompt initiation of antiviral therapy may prevent serious complications of influenza in children with cancer.

Valacyclovir: approved and off-label uses for the treatment of herpes virus infections in immunocompetent and immunocompromised adults.

IMPORTANCE OF THE FIELD: Herpes viruses are associated with a wide spectrum of clinical diseases and impose considerable morbidity and even mortality in immunosuppressed hosts. Although there is no cure for these conditions, available treatments alleviate symptoms, suppress recurrences and reduce the risk of transmission. Valacyclovir was discovered in 1988 and revolutionized the treatment of these infections by virtue of its less frequent dosing regimen, which promotes patient adherence. AREAS COVERED IN THIS REVIEW: This review focuses on the basic principles, mechanisms of action, safety and approved and off-label usage of valacyclovir in the immunocompetent and immunocompromised host. WHAT THE READER WILL GAIN: The reader will have available the current and most up-to-date information on the pharmacology of valacyclovir as well as its clinical use. TAKE HOME MESSAGE: Valacyclovir is a great alternative for the treatment of herpes infections. Now that its patent has expired, new cheaper formulations may start to appear.

Escherichia coli Pyomyositis: an emerging infectious disease among patients with hematologic malignancies.

BACKGROUND: Pyomyositis is typically caused by gram-positive bacteria, especially Staphylococcus aureus. Few cases of Escherichia coli pyomyositis have been reported, including only 1 involving a patient with a hematologic malignancy. METHODS: The clinical microbiology database at The M. D. Anderson Cancer Center (Houston, TX) was reviewed for the period January 2003 through December 2007 to identify cases of E. coli pyomyositis. Clinical characteristics, laboratory and radiologic findings, treatment, and outcomes were recorded. Available isolates underwent phylogenetic group determination, virulence genotyping, multilocus sequence typing, repetitive-element polymerase chain reaction, and pulsed-field gel electrophoresis. RESULTS: Six cases of E. coli pyomyositis were identified. All patients were receiving chemotherapy for a hematologic malignancy; 5 were severely neutropenic. Three patients became hypotensive, 2 required intensive care, and 2 (33%) died, despite receiving carbapenem therapy. All E. coli isolates were fluoroquinolone resistant; 55% produced an extended-spectrum beta-lactamase (ESBL). Five of 6 available isolates belonged to phylogenetic group B2, had similar virulence factor profiles, exhibited > 95% similar repetitive-element polymerase chain reaction profiles, and represented sequence type ST131; however, all had unique pulsed-field gel electrophoresis profiles. CONCLUSIONS: E. coli pyomyositis has emerged as a serious problem among our patients with hematologic malignancy. It usually is caused by members of E. coli ST131, a recently identified cause of fluoroquinolone-resistant, ESBL-positive E. coli infection worldwide. Awareness of this emerging syndrome and the usual causative agent is important to ensure appropriate management when febrile, neutropenic patients with hematologic malignancy exhibit signs of localized muscle infection.

Multidrug-resistant Escherichia coli bacteremia in cancer patients.

BACKGROUND: Multidrug-resistant (MDR) Escherichia coli is a serious threat to cancer patients. We aimed to determine the risk factors associated with the development of MDR E coli bacteremia in cancer patients and the possibility of horizontal transmission. METHODS: We conducted a 1:2 case-control study of 58 patients with MDR E coli bacteremia. The patient's demographics, clinical characteristics, and antibiotic use were obtained. MDR E coli was defined as resistant strains to quinolones plus 1 of the following: piperacillin, ceftazidime, or cefepime. Repetitive sequence-based polymerase chain reaction (Rep-PCR) was used to identify DNA interstrain similarities. RESULTS: Conditional multiple logistic analysis showed that admission to the hospital within the 30 days prior to infection and chemotherapy use were risk factors for infection with MDR E coli. Rep-PCR showed that, among the MDR E coli strains recovered, 48.6% showed >95% similarity, representing a possible clonal outbreak. Infection control measures were implemented and controlled this horizontal transmission. CONCLUSION: Prior admission to the hospital and previous chemotherapy were independent risk factors of acquiring MDR E coli. Molecular fingerprinting techniques detected a possible nosocomial clonal outbreak of MDR E coli, which was aborted through infection control measures.

Coliform and Escherichia coli contamination of desserts served in public restaurants from Guadalajara, Mexico, and Houston, Texas.

Bacterial enteropathogens acquired from contaminated food are the principal causes of travelers' diarrhea (TD). We evaluated desserts obtained from popular restaurants in the tourist city of Guadalajara, Mexico, and Houston, Texas, to determine coliform and Escherichia coli contamination levels and presence of diarrheagenic E. coli known to be important in TD. Contamination for all organisms was seen for desserts served in Guadalajara restaurants. Desserts should be considered as potentially risky foods for development of TD among international visitors to developing regions of the world.

Prevalence of type 2 diabetes mellitus in patients with primary hyperparathyroidism.

INTRODUCTION: To determine the prevalence of type 2 diabetes mellitus (DM) in patients with primary hyperparathyroidism. METHODS: Prevalence of type 2 DM in 609 patients with surgically verified primary hyperparathyroidism presenting between 1992 and 2003 in a tertiary care hospital setting was assessed retrospectively and compared with published data of type 2 DM prevalence in Michigan's general population. Diagnosis of type 2 DM was made on the basis of documentation in the medical record of fasting or random blood glucose level thresholds according to the 1997 American Diabetes Association criteria, history of diabetes mellitus, or therapy with antidiabetic medications. RESULTS: The crude prevalence rate of type 2 DM in patients with primary hyperparathyroidism was significantly higher than the prevalence in the Michigan general population (15.9% vs 7.8%, respectively; P<.001). However, this difference was not significant after age stratification except for the age group of 64 to 75 years. Because of the differential distribution of participants across age categories in the 2 groups, a standardized prevalence ratio (SPR) was estimated to account for the variance. After adjustment, there was no significant difference in the prevalence of DM between patients with primary hyperparathyroidism and the control population (SPR, 1.19 [95% confidence interval, 0.96-1.45]) except in men. CONCLUSION: The reported higher prevalence of type 2 DM in patients with primary hyperparathyroidism could not be confirmed in this large cohort of patients except for in older patients and in men. Because of the retrospective nature the study and the lack of appropriate controls, further studies are needed to confirm or refute these findings.