HIV infection in the elderly

In the US, an estimated 1 million people are infected with HIV, although one-third of this population are unaware of their diagnosis. While HIV infection is commonly thought to affect younger adults, there are an increasing number of patients over 50 years of age living with the condition. UNAIDS and WHO estimate that of the 40 million people living with HIV/AIDS in the world, approximately 2.8 million are 50 years and older. With the introduction of highly active antiretroviral therapy (HAART) in the mid-1990s, survival following HIV diagnosis has risen dramatically and HIV infection has evolved from an acute disease process to being managed as a chronic medical condition. As treated HIV-infected patients live longer and the number of new HIV diagnoses in older patients rise, clinicians need to be aware of these trends and become familiar with the management of HIV infection in the older patient. This article is intended for the general clinician, including geriatricians, and will review epidemiologic data and HIV treatment as well as provide a discussion on medical management issues affecting the older HIV-infected patient

The Relationship Between HIV Infection and Cardiovascular Disease

Over 30 million people are currently living with human immunodeficiency virus (HIV) infection, and over 2 million new infections occur per year. HIV has been found to directly affect vascular biology resulting in an increased risk of cardiovascular disease compared to uninfected persons. Although HIV infection can now be treated effectively with combination antiretroviral medications, significant toxicities such as hyperlipidemia, diabetes, and excess cardiovascular co-morbidity; as well as the potential for significant drug-drug interactions between HIV and cardiovascular medications, present new challenges for the management of persons infected with HIV. We first review basic principles of HIV pathogenesis and treatment and then discuss relevant clinical management strategies that will be useful for cardiologists who might be involved in the care of HIV infected patients

Is spinal tuberculosis contagious?

SummaryWhile pulmonary Mycobacterium tuberculosis infections are recognized for their public health implications, less is known about the infectiousness of extrapulmonary tuberculosis, specifically, spinal tuberculosis or Pott's disease. We present a case of spinal tuberculosis with concomitant active pulmonary tuberculosis in the absence of chest radiographic abnormalities or symptoms, and review the literature regarding infectiousness of concomitant spinal and pulmonary tuberculosis

Genetic Variation in the IL-6 and HLA-DQB1 Genes Is Associated with Spontaneous Clearance of Hepatitis C Virus Infection.

Background. Millions of people are infected with hepatitis C virus (HCV) worldwide and 30% spontaneously clear the infection. Reasons for HCV clearance without antiviral treatment are not well understood. Methods. Blood was collected for DNA analysis from patients with chronic HCV infection or evidence of spontaneous clearance. To overcome anticipated limitations of small sample size, primary analyses consisted of a candidate gene analysis of 12 preselected genes based on known association with host immunologic response to HCV infection. To further reduce the impact of multiple testing on power, a single likelihood ratio test was conducted for each gene using all associated SNPs assayed on the Illumina Quad 610/660W chip. Step-down permutation methods were used to adjust for multiple testing in all analyses. Results. Ninety-five and 62 patients with HCV chronic infection or spontaneous clearance, respectively, were included for analysis. HLA-DQB1 (p = 1.76⁎10(-5)) and IL-6 (p = 0.0007) genes were significantly associated with spontaneous HCV clearance. IL-28B was not significantly associated with spontaneous clearance (p = 0.17). Conclusion. Our whole-gene analytic strategy identified a previously unreported association of IL-6 with spontaneous clearance of HCV infection. We also confirmed the finding that HLA-DQB1 is associated with spontaneous resolution of HCV infection

Effective Detection of the 2009 H1N1 Influenza Pandemic in U.S. Veterans Affairs Medical Centers Using a National Electronic Biosurveillance System

The 2008-09 influenza season was the time in which the Department of Veterans Affairs (VA) utilized an electronic biosurveillance system for tracking and monitoring of influenza trends. The system, known as ESSENCE or Electronic Surveillance System for the Early Notification of Community-based Epidemics, was monitored for the influenza season as well as for a rise in influenza cases at the start of the H1N1 2009 influenza pandemic. We also describe trends noted in influenza-like illness (ILI) outpatient encounter data in VA medical centers during the 2008-09 influenza season, before and after the recognition of pandemic H1N1 2009 influenza virus.We determined prevalence of ILI coded visits using VA's ESSENCE for 2008-09 seasonal influenza (Sept. 28, 2008-April 25, 2009 corresponding to CDC 2008-2009 flu season weeks 40-16) and the early period of pandemic H1N1 2009 (April 26, 2009-July 31, 2009 corresponding to CDC 2008-2009 flu season weeks 17-30). Differences in diagnostic ICD-9-CM code frequencies were analyzed using Chi-square and odds ratios. There were 649,574 ILI encounters captured representing 633,893 patients. The prevalence of VA ILI visits mirrored the CDC's Outpatient ILI Surveillance Network (ILINet) data with peaks in late December, early February, and late April/early May, mirroring the ILINet data; however, the peaks seen in the VA were smaller. Of 31 ILI codes, 6 decreased and 11 increased significantly during the early period of pandemic H1N1 2009. The ILI codes that significantly increased were more likely to be symptom codes. Although influenza with respiratory manifestation (487.1) was the most common code used among 150 confirmed pandemic H1N1 2009 cases, overall it significantly decreased since the start of the pandemic.VA ESSENCE effectively detected and tracked changing ILI trends during pandemic H1N1 2009 and represents an important temporal alerting system for monitoring health events in VA facilities

Acute cardiac injury events ≤30 days after laboratory-confirmed influenza virus infection among U.S. veterans, 2010–2012

<div><p>The Rnd family of proteins, Rnd1, Rnd2 and Rnd3, are atypical Rho family GTPases, which bind to but do not hydrolyse GTP. They interact with plexins, which are receptors for semaphorins, and are hypothesised to regulate plexin signalling. We recently showed that each Rnd protein has a distinct profile of interaction with three plexins, Plexin-B1, Plexin-B2 and Plexin-B3, in mammalian cells, although it is unclear which region(s) of these plexins contribute to this specificity. Here we characterise the binary interactions of the Rnd proteins with the Rho-binding domain (RBD) of Plexin-B1 and Plexin-B2 using biophysical approaches. Isothermal titration calorimetry (ITC) experiments for each of the Rnd proteins with Plexin-B1-RBD and Plexin-B2-RBD showed similar association constants for all six interactions, although Rnd1 displayed a small preference for Plexin-B1-RBD and Rnd3 for Plexin-B2-RBD. Furthermore, mutagenic analysis of Rnd3 suggested similarities in its interaction with both Plexin-B1-RBD and Plexin-B2-RBD. These results suggest that Rnd proteins do not have a clear-cut specificity for different Plexin-B-RBDs, possibly implying the contribution of additional regions of Plexin-B proteins in conferring functional substrate selection.</p></div

Enhanced health event detection and influenza surveillance using a joint Veterans Affairs and Department of Defense biosurveillance application

<p>Abstract</p> <p>Background</p> <p>The establishment of robust biosurveillance capabilities is an important component of the U.S. strategy for identifying disease outbreaks, environmental exposures and bioterrorism events. Currently, U.S. Departments of Defense (DoD) and Veterans Affairs (VA) perform biosurveillance independently. This article describes a joint VA/DoD biosurveillance project at North Chicago-VA Medical Center (NC-VAMC). The Naval Health Clinics-Great Lakes facility physically merged with NC-VAMC beginning in 2006 with the full merger completed in October 2010 at which time all DoD care and medical personnel had relocated to the expanded and remodeled NC-VAMC campus and the combined facility was renamed the Lovell Federal Health Care Center (FHCC). The goal of this study was to evaluate disease surveillance using a biosurveillance application which combined data from both populations.</p> <p>Methods</p> <p>A retrospective analysis of NC-VAMC/Lovell FHCC and other Chicago-area VAMC data was performed using the ESSENCE biosurveillance system, including one infectious disease outbreak (Salmonella/Taste of Chicago-July 2007) and one weather event (Heat Wave-July 2006). Influenza-like-illness (ILI) data from these same facilities was compared with CDC/Illinois Sentinel Provider and Cook County ESSENCE data for 2007-2008.</p> <p>Results</p> <p>Following consolidation of VA and DoD facilities in North Chicago, median number of visits more than doubled, median patient age dropped and proportion of females rose significantly in comparison with the pre-merger NC-VAMC facility. A high-level gastrointestinal alert was detected in July 2007, but only low-level alerts at other Chicago-area VAMCs. Heat-injury alerts were triggered for the merged facility in June 2006, but not at the other facilities. There was also limited evidence in these events that surveillance of the combined population provided utility above and beyond the VA-only and DoD-only components. Recorded ILI activity for NC-VAMC/Lovell FHCC was more pronounced in the DoD component, likely due to pediatric data in this population. NC-VAMC/Lovell FHCC had two weeks of ILI activity exceeding both the Illinois State and East North Central Regional baselines, whereas Hines VAMC had one and Jesse Brown VAMC had zero.</p> <p>Conclusions</p> <p>Biosurveillance in a joint VA/DoD facility showed potential utility as a tool to improve surveillance and situational awareness in an area with Veteran, active duty and beneficiary populations. Based in part on the results of this pilot demonstration, both agencies have agreed to support the creation of a combined VA/DoD ESSENCE biosurveillance system which is now under development.</p

HIV-1 Protease, Reverse Transcriptase, and Integrase Variation

ABSTRACT HIV-1 protease (PR), reverse transcriptase (RT), and integrase (IN) variability presents a challenge to laboratories performing genotypic resistance testing. This challenge will grow with increased sequencing of samples enriched for proviral DNA such as dried blood spots and increased use of next-generation sequencing (NGS) to detect low-abundance HIV-1 variants. We analyzed PR and RT sequences from >100,000 individuals and IN sequences from >10,000 individuals to characterize variation at each amino acid position, identify mutations indicating APOBEC-mediated G-to-A editing, and identify mutations resulting from selective drug pressure. Forty-seven percent of PR, 37% of RT, and 34% of IN positions had one or more amino acid variants with a prevalence of ≥1%. Seventy percent of PR, 60% of RT, and 60% of IN positions had one or more variants with a prevalence of ≥0.1%. Overall 201 PR, 636 RT, and 346 IN variants had a prevalence of ≥0.1%. The median intersubtype prevalence ratios were 2.9-, 2.1-, and 1.9-fold for these PR, RT, and IN variants, respectively. Only 5.0% of PR, 3.7% of RT, and 2.0% of IN variants had a median intersubtype prevalence ratio of ≥10-fold. Variants at lower prevalences were more likely to differ biochemically and to be part of an electrophoretic mixture compared to high-prevalence variants. There were 209 mutations indicative of APOBEC-mediated G-to-A editing and 326 mutations nonpolymorphic treatment selected. Identification of viruses with a high number of APOBEC-associated mutations will facilitate the quality control of dried blood spot sequencing. Identifying sequences with a high proportion of rare mutations will facilitate the quality control of NGS. IMPORTANCE Most antiretroviral drugs target three HIV-1 proteins: PR, RT, and IN. These proteins are highly variable: many different amino acids can be present at the same position in viruses from different individuals. Some of the amino acid variants cause drug resistance and occur mainly in individuals receiving antiretroviral drugs. Some variants result from a human cellular defense mechanism called APOBEC-mediated hypermutation. Many variants result from naturally occurring mutation. Some variants may represent technical artifacts. We studied PR and RT sequences from >100,000 individuals and IN sequences from >10,000 individuals to quantify variation at each amino acid position in these three HIV-1 proteins. We performed analyses to determine which amino acid variants resulted from antiretroviral drug selection pressure, APOBEC-mediated editing, and naturally occurring variation. Our results provide information essential to clinical, research, and public health laboratories performing genotypic resistance testing by sequencing HIV-1 PR, RT, and IN

Emergence of Hemagglutinin Mutations during the Course of Influenza Infection

Influenza remains a significant cause of disease mortality. The ongoing threat of influenza infection is partly attributable to the emergence of new mutations in the influenza genome. Among the influenza viral gene products, the hemagglutinin (HA) glycoprotein plays a critical role in influenza pathogenesis, is the target for vaccines and accumulates new mutations that may alter the efficacy of immunization. To study the emergence of HA mutations during the course of infection, we employed a deep-targeted sequencing method. We used samples from 17 patients with active H1N1 or H3N2 influenza infections. These patients were not treated with antivirals. In addition, we had samples from five patients who were analyzed longitudinally. Thus, we determined the quantitative changes in the fractional representation of HA mutations during the course of infection. Across individuals in the study, a series of novel HA mutations directly altered the HA coding sequence were identified. Serial viral sampling revealed HA mutations that either were stable, expanded or were reduced in representation during the course of the infection. Overall, we demonstrated the emergence of unique mutations specific to an infected individual and temporal genetic variation during infection

Mapping MOS-HIV to HUI3 and EQ-5D-3L in Patients With HIV

Objectives: The Medical Outcomes Study HIV Health Survey (MOS-HIV) is frequently used in HIV clinical trials; however, scores generated from the MOS-HIV are not suited for cost-effectiveness analyses as they do not assign utility values to health states. Our objective was to estimate and externally validate several mapping algorithms to predict Health Utilities Index Mark 3 (HUI3) and EQ-5D-3L utility values from the MOS-HIV. Methods: We developed and validated mapping algorithms using data from two HIV clinical trials. Data from the first trial (n = 367) formed the estimation data set for the HUI3 (4,610 observations) and EQ-5D-3L (4,662 observations) mapping algorithms; data from the second trial (n = 168) formed the HUI3 (1,135 observations) and EQ-5D-3L (1,152 observations) external validation data set. We compared ordinary least squares (OLS) models of increasing complexity with the more flexible two-part, beta regression, and finite mixture models. We assessed model performance using mean absolute error (MAE) and mean squared error (MSE). Results: The OLS model that used MOS-HIV dimension scores along with squared terms gave the best HUI3 predictions (mean observed 0.84; mean predicted 0.80; MAE 0.0961); the finite mixture model gave the best EQ-5D-3L predictions (mean observed 0.90; mean predicted 0.88; MAE 0.0567). All models produced higher prediction errors at the lower end of the HUI3 and EQ-5D-3L score ranges