Hepatitis C virus screening practices and seropositivity among US veterans born during 1945 - 1965.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) and the United States Preventive Services Task Force (USPSTF) recently augmented risk-based hepatitis C (HCV) screening guidelines with a recommendation to perform one-time screening in all persons born during 1945 - 1965, a birth cohort known to have a higher prevalence of HCV. We sought to estimate the proportion of veterans seen at the Atlanta VA Medical Center (AVAMC) who had ever been screened for HCV infection by birth year. METHODS: We used an administrative database of all veterans seen at the AVAMC between January 1, 2011 and December 31, 2011, and a laboratory generated list of all HCV antibody tests and HCV RNA viral loads that were performed at the AVAMC to determine receipt of screening and HCV antibody positivity. Odds ratios and 95% confidence intervals were estimated using SAS version 9.2 (SAS institute, Cary, North Carolina). RESULTS: HCV antibody testing had ever been performed on 48% (41,556) of the veterans seen in 2011; 10% of those tested had a positive antibody. Confirmatory viral loads were performed in 96% of those with a positive antibody screen. Those born during 1945 - 1965 were more likely to have a HCV antibody performed when compared with those born in other years (54% vs. 41%, odds ratio [OR] 1.70, 95% Confidence Interval [CI] 1.65-1.74). Among veterans ever tested for HCV antibody (n = 41,556), those born during 1945 - 1965 were 6 times more likely to have a positive HCV antibody (15% vs. 3%, OR 5.87, 95% CI 5.32-6.78), and 3 times more likely to have chronic HCV infection (76% vs. 50%, OR 3.25, 95% CI 2.65-4.00). CONCLUSIONS: Nearly half of the veterans seen in 2011 at the AVAMC had ever been tested for HCV infection. When examined by birth cohort, over half of the veterans born during 1945 - 1965 had been screened for HCV and 15% of those screened had a positive HCV antibody. Our findings confirm the increased prevalence of HCV infection in persons born during 1945 - 1965 as identified in the updated CDC and USPSTF recommendations

Methicillin-resistant Staphylococcus aureus in HIV-infected patients

Concordant with the emergence of methicillin-resistant Staphylococcus aureus (MRSA) in the community setting, colonization and infections with this pathogen have become a prevalent problem among the human immunodeficiency virus (HIV)-positive population. A variety of different host- and, possibly, pathogen-related factors may play a role in explaining the increased prevalence and incidence observed. In this article, we review pathophysiology, epidemiology, clinical manifestations, and treatment of MRSA in the HIV-infected population

A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus

<p>Abstract</p> <p>Background</p> <p>The major hurdle in the treatment of Human Immunodeficiency virus type 1 (HIV-1) includes the development of drug resistance-associated mutations in the target regions of the virus. Since reverse transcriptase (RT) is essential for HIV-1 replication, several nucleoside analogues have been developed to target RT of the virus. Clinical studies have shown that mutations at RT codon 65 and 74 which are located in β3-β4 linkage group of finger sub-domain of RT are selected during treatment with several RT inhibitors, including didanosine, deoxycytidine, abacavir and tenofovir. Interestingly, the co-selection of K65R and L74V is rare in clinical settings. We have previously shown that K65R and L74V are incompatible and a R→K reversion occurs at codon 65 during replication of the virus. Analysis of the HIV resistance database has revealed that similar to K65R+L74V, the double mutant K65R+L74I is also rare. We sought to compare the impact of L→V <it>versus </it>L→I change at codon 74 in the background of K65R mutation, on the replication of doubly mutant viruses.</p> <p>Methods</p> <p>Proviral clones containing K65R, L74V, L74I, K65R+L74V and K65R+L74I RT mutations were created in pNL4-3 backbone and viruses were produced in 293T cells. Replication efficiencies of all the viruses were compared in peripheral blood mononuclear (PBM) cells in the absence of selection pressure. Replication capacity (RC) of mutant viruses in relation to wild type was calculated on the basis of antigen p24 production and RT activity, and paired analysis by student t-test was performed among RCs of doubly mutant viruses. Reversion at RT codons 65 and 74 was monitored during replication in PBM cells. In vitro processivity of mutant RTs was measured to analyze the impact of amino acid changes at RT codon 74.</p> <p>Results</p> <p>Replication kinetics plot showed that all of the mutant viruses were attenuated as compared to wild type (WT) virus. Although attenuated in comparison to WT virus and single point mutants K65R, L74V and L74I; the double mutant K65R+L74I replicated efficiently in comparison to K65R+L74V mutant. The increased replication capacity of K65R+L74I viruses in comparison to K65R+L74V viruses was significant at multiplicity of infection 0.01 (p = 0.0004). Direct sequencing and sequencing after population cloning showed a more pronounced reversion at codon 65 in viruses containing K65R+L74V mutations in comparison to viruses with K65R+L74I mutations. In vitro processivity assays showed increased processivity of RT containing K65R+L74I in comparison to K65R+L74V RT.</p> <p>Conclusions</p> <p>The improved replication kinetics of K65R+L74I virus in comparison to K65R+L74V viruses was due to an increase in the processivity of RT containing K65R+L74I mutations. These observations support the rationale behind structural functional analysis to understand the interactions among unique RT mutations that may emerge during the treatment with specific drug regimens.</p

Cohort Profile: The HIV Atlanta Veterans Affairs Cohort Study (HAVACS).

The originally published version of this Profile contained an error in one of the author names. Vince D. Marconi should have read Vince C. Marconi. This has now been corrected

Transcriptional down-regulation of ccr5 in a subset of HIV+ controllers and their family members.

HIV +Elite and Viremic controllers (EC/VCs) are able to control virus infection, perhaps because of host genetic determinants. We identified 16% (21 of 131) EC/VCs with CD4 +T cells with resistance specific to R5-tropic HIV, reversed after introduction of ccr5. R5 resistance was not observed in macrophages and depended upon the method of T cell activation. CD4 +T cells of these EC/VCs had lower ccr2 and ccr5 RNA levels, reduced CCR2 and CCR5 cell-surface expression, and decreased levels of secreted chemokines. T cells had no changes in chemokine receptor mRNA half-life but instead had lower levels of active transcription of ccr2 and ccr5, despite having more accessible chromatin by ATAC-seq. Other nearby genes were also down-regulated, over a region of ~500 kb on chromosome 3p21. This same R5 resistance phenotype was observed in family members of an index VC, also associated with ccr2/ccr5 down-regulation, suggesting that the phenotype is heritable

Cost-Effectiveness of HIV Screening in STD Clinics, Emergency Departments, and Inpatient Units: A Model-Based Analysis

Identifying and treating persons with human immunodeficiency virus (HIV) infection early in their disease stage is considered an effective means of reducing the impact of the disease. We compared the cost-effectiveness of HIV screening in three settings, sexually transmitted disease (STD) clinics serving men who have sex with men, hospital emergency departments (EDs), settings where patients are likely to be diagnosed early, and inpatient diagnosis based on clinical manifestations.We developed the Progression and Transmission of HIV/AIDS model, a health state transition model that tracks index patients and their infected partners from HIV infection to death. We used program characteristics for each setting to compare the incremental cost per quality-adjusted life year gained from early versus late diagnosis and treatment. We ran the model for 10,000 index patients for each setting, examining alternative scenarios, excluding and including transmission to partners, and assuming HAART was initiated at a CD4 count of either 350 or 500 cells/µL. Screening in STD clinics and EDs was cost-effective compared with diagnosing inpatients, even when including only the benefits to the index patients. Screening patients in STD clinics, who have less-advanced disease, was cost-effective compared with ED screening when treatment with HAART was initiated at a CD4 count of 500 cells/µL. When the benefits of reduced transmission to partners from early diagnosis were included, screening in settings with less-advanced disease stages was cost-saving compared with screening later in the course of infection. The study was limited by a small number of observations on CD4 count at diagnosis and by including transmission only to first generation partners of the index patients.HIV prevention efforts can be advanced by screening in settings where patients present with less-advanced stages of HIV infection and by initiating treatment with HAART earlier in the course of infection

Development and Validation of an Algorithm to Identify Patients Newly Diagnosed with HIV Infection from Electronic Health Records

An algorithm was developed that identifies patients with new diagnoses of HIV infection by the use of electronic health records. It was based on the sequence of HIV diagnostic tests, entry of ICD-9-CM diagnostic codes, and measurement of HIV-1 plasma RNA levels in persons undergoing HIV testing from 2006 to 2012 at four large urban Veterans Health Administration (VHA) facilities. Source data were obtained from the VHA National Corporate Data Warehouse. Chart review was done by a single trained abstractor to validate site-level data regarding new diagnoses. We identified 1,153 patients as having a positive HIV diagnostic test within the VHA. Of these, 57% were determined to have prior knowledge of their HIV status from testing at non-VHA facilities. An algorithm based on the sequence and results of available laboratory tests and ICD-9-CM entries identified new HIV diagnoses with a sensitivity of 83%, specificity of 86%, positive predictive value of 85%, and negative predictive value of 90%. There were no meaningful demographic or clinical differences between newly diagnosed patients who were correctly or incorrectly classified by the algorithm. We have validated a method to identify cases of new diagnosis of HIV infection in large administrative datasets. This method, which has a sensitivity of 83%, specificity of 86%, positive predictive value of 85%, and negative predictive value of 90% can be used in analyses of the epidemiology of newly diagnosed HIV infection

A comparison of HAART outcomes between the US military HIV Natural History Study (NHS) and HIV Atlanta Veterans Affairs Cohort Study (HAVACS).

INTRODUCTION: The Department of Defense (DoD) and the Department of Veterans Affairs (VA) provide comprehensive HIV treatment and care to their beneficiaries with open access and few costs to the patient. Individuals who receive HIV care in the VA have higher rates of substance abuse, homelessness and unemployment than individuals who receive HIV care in the DoD. A comparison between individuals receiving HIV treatment and care from the DoD and the VA provides an opportunity to explore the impact of individual-level characteristics on clinical outcomes within two healthcare systems that are optimized for clinic retention and medication adherence. METHODS: Data were collected on 1065 patients from the HIV Atlanta VA Cohort Study (HAVACS) and 1199 patients from the US Military HIV Natural History Study (NHS). Patients were eligible if they had an HIV diagnosis and began HAART between January 1, 1996 and June 30, 2010. The analysis examined the survival from HAART initiation to all-cause mortality or an AIDS event. RESULTS: Although there was substantial between-cohort heterogeneity and the 12-year survival of participants in NHS was significantly higher than in HAVACS in crude analyses, this survival disparity was reduced from 21.5% to 1.6% (mortality only) and 26.8% to 4.1% (combined mortality or AIDS) when controlling for clinical and demographic variables. CONCLUSION: We assessed the clinical outcomes for individuals with HIV from two very similar government-sponsored healthcare systems that reduced or eliminated many barriers associated with accessing treatment and care. After controlling for clinical and demographic variables, both 12-year survival and AIDS-free survival rates were similar for the two study cohorts who have open access to care and medication despite dramatic differences in socioeconomic and behavioral characteristics