Epidemiological and viral characteristics of undiagnosed HIV infections in Botswana.

BACKGROUND: HIV-1 is endemic in Botswana. The country's primary challenge is identifying people living with HIV who are unaware of their status. We evaluated factors associated with undiagnosed HIV infection using HIV-1 phylogenetic, behavioural, and demographic data. METHODS: As part of the Botswana Combination Prevention Project, 20% of households in 30 villages were tested for HIV and followed from 2013 to 2018. A total of 12,610 participants were enrolled, 3596 tested HIV-positive at enrolment, and 147 participants acquired HIV during the trial. Extensive socio-demographic and behavioural data were collected from participants and next-generation sequences were generated for HIV-positive cases. We compared three groups of participants: (1) those previously known to be HIV-positive at enrolment (n = 2995); (2) those newly diagnosed at enrolment (n = 601) and (3) those who tested HIV-negative at enrolment but tested HIV-positive during follow-up (n = 147). We searched for differences in demographic and behavioural factors between known and newly diagnosed group using logistic regression. We also compared the topology of each group in HIV-1 phylogenies and used a genetic diversity-based algorithm to classify infections as recent (< 1 year) or chronic (≥ 1 year). RESULTS: Being male (aOR = 2.23) and younger than 35 years old (aOR = 8.08) was associated with undiagnosed HIV infection (p < 0.001), as was inconsistent condom use (aOR = 1.76). Women were more likely to have undiagnosed infections if they were married, educated, and tested frequently. For men, being divorced increased their risk. The genetic diversity-based algorithm classified most incident infections as recent (75.0%), but almost none of known infections (2.0%). The estimated proportion of recent infections among new diagnoses was 37.0% (p < 0.001). CONCLUSION: Our results indicate that those with undiagnosed infections are likely to be young men and women who do not use condoms consistently. Among women, several factors were predictive: being married, educated, and testing frequently increased risk. Men at risk were more difficult to delineate. A sizeable proportion of undiagnosed infections were recent based on a genetic diversity-based classifier. In the era of "test and treat all", pre-exposure prophylaxis may be prioritized towards individuals who self-identify or who can be identified using these predictors in order to halt onward transmission in time.

High Prevalence of Biofilms on Retrieved Implants from Aseptic Pseudarthrosis Cases.

INTRODUCTION: Recent literature has associated pseudarthrosis and pedicle screw loosening with subchronic infection at the pedicle of the vertebra. The positive culture results of a previous retrieval analysis show that such patients have a high frequency of bacterial contamination. The objective of this study is to visually capture the architecture of these undiagnosed infections, which have been described in other studies as biofilms on supposedly "aseptic" screw loosening. METHODS: Explants from 10 consecutive patients undergoing revision spine surgery for pseudarthrosis were collected and fixed in glutaraldehyde solution. Each of these implants was imaged thoroughly by using scanning electron microscopy and x-ray spectroscopy to evaluate the architecture of the biofilm. Additionally, eight patient swabs from tissues around the implants were sent for cultures to assess bacterial infiltration in tissues beyond the biofilm. The implants were also analyzed using energy dispersive x-ray spectroscopy. The exclusion criteria included clinically diagnosed infection (current or previous) and/or mechanical failure of the implant due to falls/accidents. RESULTS: The study was successful in capturing the visual architecture of the biofilm on retrieved implants. A total of 77% of pseudarthrosis cases presented with loose pedicle screws, which were diagnosed by a preoperative computed tomography scan showing radiolucency along the screw track and were confirmed intraoperatively, and 72% of the cases showed biofilm on explants. CONCLUSIONS: In the absence of the clinical presentation of infection, impregnated bacteria could form a biofilm around an implant, and this biofilm can remain undetected via contemporary diagnostic methods, including swabbing. Implant biofilm is frequently present in "aseptic" pseudarthrosis cases.

Advanced liver fibrosis and care continuum in emergency department patients with chronic hepatitis C.

BACKGROUND: FIB-4, a non-invasive serum fibrosis index (which includes age, ALT, AST, and platelet count), is frequently available during ED visits. Our objective was to define 1-year HCV-related care outcomes of ED patients with known HCV, for the overall group, and both those with and without advanced fibrosis. METHODS: As part of an ongoing HCV linkage-to-care (LTC) program, HCV-infected ED patients were identified retrospectively via medical record review. Components of FIB-4 were abstracted, and patients with an FIB-4 > 3.25 were classified with advanced fibrosis and characterized with regards to downstream HCV care continuum outcomes at one-year after enrollment. RESULTS: Of the 113 patients with known HCV, 38 (33.6%) had advanced fibrosis. One-year outcomes along the HCV care continuum after ED encounter for 'all' 113, 75 'without advanced fibrosis', and 38 'advanced fibrosis' patients, respectively, were as follows: agreeing to be linked to care [106 (93.8%), 72 (96.0%), 34 (89.5%)]; LTC [38 (33.6%), 21 (28.0%), 17 (44.7%)]; treatment initiation among those linked [16 (42.1%), 9 (42.9%), 7 (41.2%)]; sustained virologic response 4 weeks post-treatment among those treated [15 (93.8%), 9 (100.0%), 6 (85.7%)]; documented all-cause mortality [10 (8.8%), 3 (4.0%), 7 (18.4%)]. Notably, 70% of those who died had advanced fibrosis. For those with advanced liver fibrosis, all-cause mortality was significantly higher, than those without (18.4% versus 4.0%, p = 0.030). CONCLUSIONS: Over one-third of HCV-infected ED patients have advanced liver fibrosis, incomplete LTC, and higher mortality, suggesting this readily-available FIB-4 might be used to prioritize LTC services for those with advanced fibrosis.

Estimating the HIV undiagnosed population in Catalonia, Spain: descriptive and comparative data analysis to identify differences in MSM stratified by migrant and Spanish-born population.

OBJECTIVE: Undiagnosed HIV continues to be a hindrance to efforts aimed at reducing incidence of HIV. The objective of this study was to provide an estimate of the HIV undiagnosed population in Catalonia and compare the HIV care cascade with this step included between high-risk populations. METHODS: To estimate HIV incidence, time between infection and diagnosis and the undiagnosed population stratified by CD4 count, we used the ECDC HIV Modelling Tool V.1.2.2. This model uses data on new HIV and AIDS diagnoses from the Catalan HIV/AIDS surveillance system from 2001 to 2013. Data used to estimate the proportion of people enrolled, on ART and virally suppressed in the HIV care cascade were derived from the PISCIS cohort. RESULTS: The total number of people living with HIV (PLHIV) in Catalonia in 2013 was 34 729 (32 740 to 36 827), with 12.3% (11.8 to 18.1) of whom were undiagnosed. By 2013, there were 8458 (8101 to 9079) Spanish-born men who have sex with men (MSM) and 2538 (2334 to 2918) migrant MSM living with HIV in Catalonia. A greater proportion of migrant MSM than local MSM was undiagnosed (32% vs 22%). In the subsequent steps of the HIV care cascade, migrants MSM experience greater losses than the Spanish-born MSM: in retention in care (74% vs 55%), in the proportion on combination antiretroviral treatment (70% vs 50%) and virally suppressed (65% vs 46%). CONCLUSIONS: By the end of 2013, there were an estimated 34 729 PLHIV in Catalonia, of whom 4271 were still undiagnosed. This study shows that the Catalan epidemic of HIV has continued to expand with the key group sustaining HIV transmission being MSM living with undiagnosed HIV.

Reduction in undiagnosed HIV infection in the European Union/European Economic Area, 2012 to 2016.

It is well-documented that early HIV diagnosis and linkage to care reduces morbidity and mortality as well as HIV transmission. We estimated the median time from HIV infection to diagnosis in the European Union/European Economic Area (EU/EEA) at 2.9 years in 2016, with regional variation. Despite evidence of a decline in the number of people living with undiagnosed HIV in the EU/EEA, many remain undiagnosed, including 33% with more advanced HIV infection (CD4 < 350 cells/mm3).

Undiagnosed HIV and Hepatitis C infection in people who inject drugs: From new evidence to better practice.

BACKGROUND: The objective of this study was to estimate the proportion of undiagnosed HIV or Hepatitis C virus (HCV) infection and to assess the risk factors associated with an undiagnosed infection. METHODS: A questionnaire was distributed among people who inject drugs (PWID) in harm reduction centres in Catalonia, Spain 2008-2012 (n=2243). Self-report of HIV and HCV was compared to oral fluid tests to calculate the proportion of undiagnosed infection. Associations of undiagnosed HIV and HCV with age, origin, risk and protective factors of infection and services use were calculated using a Poisson regression model with robust variance. RESULTS: The sensitivity of HIV self-report was 78.5% (75.2%-81.5%) and of HCV was 81.2% (79.1%-83.2%), being lower in younger and foreign-born PWID. Specificity for HCV was 55.9% (51.6%-60.1%). PWID who engaged in infection risk behaviors had lower risk of being undiagnosed. Being foreign-born and younger increased the risk of undiagnosed infection. PWID who had not accessed medical care in the last 6months had 1.46 (1.10-1.93) times more risk of undiagnosed HIV and 1.37 (1.11-1.70) times more risk of undiagnosed HCV. CONCLUSION: Outreach programmes are essential to provide PWID, specially foreign-born and younger PIWD, access to HIV and HCV test.

MSM in Bogotá are living with HIV for extended periods without diagnosis or treatment.

We examined recency of infection in serum samples obtained from 69 newly identified HIV-positive cases in a sample of 1000 men who have sex with men (MSM) in Bogotá. HIV antibody avidity assays were performed using the Architect HIV Ag/AB combo. Avidity indices ranged from 0.62 to 1.22, with a cut-off score below 0.80 indicative of recent infection. Two samples were classified as recent, six fell within the gray zone (0.75 to 0.85), and the remaining 61 were considered established infections. Results provided evidence of widespread, long-term, undiagnosed HIV infection, as well as an estimate of one-year incidence at .25 in the population of MSM in Bogotá. This incidence rate is approximately 8.5 times the rate estimated for the general adult population in Colombia. The large proportion of newly diagnosed cases found among individuals with established infections indicates that many MSM in Bogotá are living with HIV for extended periods without being diagnosed and treated. Greater efforts to detect and treat undiagnosed infections are crucial to decrease HIV incidence and increase maximum effectiveness of medical intervention. Given the over-representation of MSM and transgender women in the HIV epidemic in Colombia, such efforts should specifically target this population.

Evaluation of the Centers for Disease Control and Prevention Recommendations for Hepatitis C Virus Testing in an Urban Emergency Department.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) recommends 1-time hepatitis C virus (HCV) testing in the 1945-1965 birth cohort, in addition to targeted risk-based testing. Emergency departments (EDs) are key venues for HCV testing because of the population served and success in HIV screening. We determined the burden of undocumented HCV infection in our ED, providing guidance for implementation of ED-based HCV testing. METHODS: An 8-week seroprevalence study was conducted in an urban ED in 2013. All patients with excess blood collected for clinical purposes were included. Demographic and clinical information including documented HCV infection was obtained from electronic medical records. HCV antibody testing was performed on excess samples. RESULTS: Of 4713 patients, 652 (13.8%) were HCV antibody positive. Of these, 204 (31.3%) had undocumented HCV infection. Among patients with undocumented infections, 99 (48.5%) would have been diagnosed based on birth cohort testing, and an additional 54 (26.5%) would be identified by risk-based testing. If our ED adhered to the CDC guidelines, 51 (25.0%) patients with undocumented HCV would not have been tested. Given an estimated 7727 unique ED patients with HCV infection in a 1-year period, birth cohort plus risk-based testing would identify 1815 undocumented infections, and universal testing would identify additional 526 HCV-infected persons. CONCLUSIONS: Birth cohort-based testing would augment identification of undocumented HCV infections in this ED 2-fold, relative to risk-based testing only. However, our data demonstrate that one-quarter of infections would remain undiagnosed if current CDC birth cohort recommendations were employed, suggesting that in high-risk urban ED settings a practice of universal 1-time testing might be more effective.