Viral blood-borne infections testing and linkage to care cascade among persons who experience homelessness in the United States: a systematic review and meta-analysis.

BACKGROUND: Persons who experience homelessness remain at increased risk for three viral blood-borne infections: human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). We assessed the yield of testing and linkage to care programs targeting this population for these infections in the United States (US). METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Central for peer-reviewed articles through August 27, 2020. Additionally, we searched the grey literature. Two individuals independently reviewed all relevant studies to check for eligibility and extracted data for each step in the care cascade. We used random-effects model to generate weighted pooled proportions to assess yield at each step. Cumulative proportions were calculated as products of adjacent-step pooled proportions. We quantitatively synthesized data from the studies that focused on non-drug injecting individuals. RESULTS: We identified 24 studies published between 1996-2019 conducted in 19 US states. Seventeen studies screened for HIV, 12 for HCV, and two screened for HBV. For HIV, 72% of approached were recruited, 64% had valid results, 4% tested positive, 2% were given results, and 1% were referred and attended follow-up. Of positives, 25% were referred to treatment and started care. For HCV, 69% of approached were recruited, 63% had valid results, 16% tested positive, 14% were given results, and 3% attended follow-up. Of positives, 30% were referred for treatment and 19% started care. The yield at each care cascade step differs widely by recruitment strategy (for example, for HIV: 71.6% recruited of reached under service-based with zero yield under healthcare facility-based and outreach). CONCLUSIONS: A very large proportion of this population reached for HIV and HCV care were lost in the follow-up steps and never received treatment. Future programs should examine drop-out reasons and intervene to reduce health disparities in this population.

Decreased Time to Viral Suppression After Implementation of Targeted Testing and Immediate Initiation of Treatment of Acute Human Immunodeficiency Virus Infection Among Men Who Have Sex With Men in Amsterdam.

BACKGROUND: Men who have sex with men (MSM) with acute human immunodeficiency virus (HIV) infection (AHI) are a key source of new infections. To curb transmission, we implemented a strategy for rapid AHI diagnosis and immediate initiation of combination antiretroviral therapy (cART) in Amsterdam MSM. We assessed its effectiveness in diagnosing AHI and decreasing the time to viral suppression. METHODS: We included 63 278 HIV testing visits in 2008-2017, during which 1013 MSM were diagnosed. Standard of care (SOC) included HIV diagnosis confirmation in < 1 week and cART initiation in < 1 month. The AHI strategy comprised same-visit diagnosis confirmation and immediate cART. Time from diagnosis to viral suppression was assessed for 3 cART initiation periods: (1) 2008-2011: cART initiation if CD4 < 500 cells/µL (SOC); (2) January 2012-July 2015: cART initiation if CD4 < 500 cells/µL, or if AHI or early HIV infection (SOC); and (3a) August 2015-June 2017: universal cART initiation (SOC) or (3b) August 2015-June 2017 (the AHI strategy). RESULTS: Before implementation of the AHI strategy, the proportion of AHI among HIV diagnoses was 0.6% (5/876); after implementation this was 11.0% (15/137). Median time (in days) to viral suppression during periods 1, 2, 3a, and 3b was 584 (interquartile range [IQR], 267-1065), 230 (IQR, 132-480), 95 (IQR, 63-136), and 55 (IQR, 31-72), respectively (P < .001). CONCLUSIONS: Implementing the AHI strategy was successful in diagnosing AHI and significantly decreasing the time between HIV diagnosis and viral suppression.

Age-group-targeted testing for COVID-19 as a new prevention strategy.

Robust testing and tracing are key to fighting the menace of coronavirus disease 2019 (COVID-19). This outbreak has progressed with tremendous impact on human life, society and economy. In this paper, we propose an age-structured SIQR model to track the progression of the pandemic in India, Italy and USA, taking into account the different age structures of these countries. We have made predictions about the disease dynamics, identified the most infected age groups and analysed the effectiveness of social distancing measures taken in the early stages of infection. The basic reproductive ratio R 0 has been numerically calculated for each country. We propose a strategy of age-targeted testing, with increased testing in the most proportionally infected age groups. We observe a marked flattening of the infection curve upon simulating increased testing in the 15-40 year age groups in India. Thus, we conclude that social distancing and widespread testing are effective methods of control, with emphasis on testing and identifying the hot spots of highly infected populations. It has also been suggested that a complete lockdown, followed by lockdowns in selected regions, is more effective than the reverse.

Routine HIV testing program in the University Infectious Diseases Centre in Lithuania: a four-year analysis.

BACKGROUND: HIV transmission remains a major concern in Eastern Europe, and too many people are diagnosed late. Expanded testing strategies and early and appropriate access to care are required. Infectious disease departments might be targets for expanded HIV testing owing to the intense passage of key patient populations that carry indicators of HIV disease. Our objective was to evaluate the feasibility and clinical effectiveness of a fully integrated, opt-out routine, rapid HIV testing program. METHODS: A retrospective four-year study of a screening program was conducted from 2010 through 2014. The program was divided into two periods: from 2010 to 2012 (pilot study) and from 2013 to 2014. The pilot study consisted of routine HIV testing of patients aged 18-55 that were hospitalized in one department. In the second period, all inpatients aged 18-65 were eligible. Targeted testing was conducted in the other inpatient department during the pilot study and the outpatient department during both periods. RESULTS: During the pilot study, 2203 patients were hospitalized, 1314 (59.6%) were eligible, 954 (72.6%) were tested, and 3 (0.31%) were newly diagnosed HIV-positive. In the second period, 4911 patients were hospitalized, 3727 (75.9%) were eligible, 3303 (88.6%) were tested, and 7 (0.21%) were HIV-positive. In total, 2800 targeted tests were performed, and 4 (0.14%) patients tested positive with newly discovered HIV. All 14 newly diagnosed patients were provided with care. Comparing cumulative groups of routine and targeted testing, the HIV prevalence was 0.23% vs. 0.14% (p = 0.40) and was above the reported cost-effectiveness threshold of 0.1% (p = 0.012). A lower proportion of advanced disease and a higher proportion of heterosexually transmitted infection were found in the routine testing group. CONCLUSION: Routine HIV testing in admissions of infectious diseases is acceptable, feasible, sustainable and clinically effective. Compared to targeted testing, routine testing helped to discover more patients in earlier stages and those with heterosexually transmitted HIV infection.

Care Cascade for targeted tuberculosis testing and linkage to Care in Homeless Populations in the United States: a meta-analysis.

BACKGROUND: Homelessness increases the risk of tuberculosis (TB) disease and latent TB infection (LTBI), but persons experiencing homelessness often lack access to testing and treatment. We assessed the yield of TB testing and linkage to care for programs targeting homeless populations in the United States. METHODS: We conducted a comprehensive search of peer-reviewed and grey literature, adapting Cochrane systematic review methods. Two reviewers independently assessed study eligibility and abstracted key data on the testing to care cascade: number of persons reached, recruited for testing, tested for LTBI, with valid test results, referred to follow-up care, and initiating care. We used random effects to calculate pooled proportions and 95% confidence intervals (CI) of persons retained in each step via inverse-variance weighted meta-analysis, and cumulative proportions as products of adjacent step proportions. RESULTS: We identified 23 studies published between 1986 and 2014, conducted in 12 states and 15 cities. Among studies using tuberculin skin tests (TST) we found that 93.7% (CI 72.4-100%) of persons reached were recruited, 97.9% (89.3-100%) of those recruited had tests placed, 85.5% (78.6-91.3%) of those with tests placed returned for reading, 99.9% (99.6-100%) of those with tests read had valid results, and 24.7% (21.0-28.5%) with valid results tested positive. All persons testing positive were referred to follow-up care, and 99.8% attended at least one session of follow-up care. Heterogeneity was high for most pooled proportions. For a hypothetical cohort of 1000 persons experiencing homelessness reached by a targeted testing program using TST, an estimated 917 were tested, 194 were positive, and all of these initiated follow-up care. CONCLUSIONS: Targeted TB testing of persons experiencing homelessness appears effective in detecting LTBI and connecting persons to care and potential treatment. Future evaluations should assess diagnostic use of interferon gamma release assays and completion of treatment, and costs of testing and treatment.

Clinical indicators associated with HIV acquisition in the United States Air Force.

Mandatory HIV screening of United States Air Force (USAF) personnel every two years effectively identifies incident cases, however testing frequency limits the ability to detect early HIV infection. Identifying clinical indicators of HIV in the USAF population is necessary to develop a supplemental provider-based targeted testing strategy. We conducted a matched case-control study of male active duty USAF personnel with a new HIV diagnosis (n = 452) between 1996 and 2011 matched to five randomly selected controls (n = 2176). The relationship between clinical diagnoses, determined by ICD-9 codes, and HIV infection was assessed using conditional logistic regression. In unadjusted analyses of ICD-9 codes ever and within the last two years before HIV diagnosis, the conditional odds of HIV infection were greater in those with clinical signs and symptoms of HIV (cOR 5.05, 95% CI 4.00-6.39), mental health diagnoses (cOR 2.61, 95% CI 1.86-3.67), and STI diagnoses (cOR 2.33, 95% CI 1.50-3.60). Compared to those with ≤10 medical encounters in the two years prior to HIV diagnosis, individuals with 11-35 medical encounters (cOR 2.19, 95% CI 1.73-2.79) and >35 medical encounters (cOR 4.15, 95% CI 2.69-6.39) had a higher odds of HIV acquisition. In multivariate analyses, clinical signs and symptoms of HIV within the last two years of HIV diagnosis (cOR 4.10, 95% CI 3.22-5.22) and ever having a mental health diagnosis (cOR 1.97, 95% CI 1.44-2.70) remained significant (p < .01). Clinical encounters, particularly those featuring clinical signs and symptoms of HIV or a history of mental health complaints, provide an opportunity for targeted testing as a supplement to mandated testing at two-year intervals. Provider education to increase HIV testing in persons at risk would enhance early HIV diagnosis and potentially reduce forward transmission in the USAF population.

SARS-CoV-2 control on a large urban college campus without mass testing.

OBJECTIVE: A small percentage of universities and colleges conducted mass SARS-CoV-2 testing. However, universal testing is resource-intensive, strains national testing capacity, and false negative tests can encourage unsafe behaviors. PARTICIPANTS: A large urban university campus. METHODS: Virus control centered on three pillars: mitigation, containment, and communication, with testing of symptomatic and a random subset of asymptomatic students. RESULTS: Random surveillance testing demonstrated a prevalence among asymptomatic students of 0.4% throughout the term. There were two surges in cases that were contained by enhanced mitigation and communication combined with targeted testing. Cumulative cases totaled 445 for the term, most resulting from unsafe undergraduate student behavior and among students living off-campus. A case rate of 232/10,000 undergraduates equaled or surpassed several peer institutions that conducted mass testing. CONCLUSIONS: An emphasis on behavioral mitigation and communication can control virus transmission on a large urban campus combined with a limited and targeted testing strategy.

High-Throughput Adaptable SARS-CoV-2 Screening for Rapid Identification of Dominant and Emerging Regional Variants.

OBJECTIVES: Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant strains can be associated with increased transmissibility, more severe disease, and reduced effectiveness of treatments. To improve the availability of regional variant surveillance, we describe a variant genotyping system that is rapid, accurate, adaptable, and able to detect new low-level variants built with existing hospital infrastructure. METHODS: We used a tiered high-throughput SARS-CoV-2 screening program to characterize variants in a supraregional health system over 76 days. Combining targeted reverse transcription-polymerase chain reaction (RT-PCR) and selective sequencing, we screened SARS-CoV-2 reactive samples from all hospitals within our health care system for genotyping dominant and emerging variants. RESULTS: The median turnaround for genotyping was 2 days using the high-throughput RT-PCR-based screen, allowing us to rapidly characterize the emerging Delta variant. In our population, the Delta variant is associated with a lower cycle threshold value, lower age at infection, and increased vaccine-breakthrough cases. Detection of low-level and potentially emerging variants highlights the utility of a tiered approach. CONCLUSIONS: These findings underscore the need for fast, low-cost, high-throughput monitoring of regional viral sequences as the pandemic unfolds and the emergence of SARS-CoV-2 variants increases. Combining RT-PCR-based screening with selective sequencing allows for rapid genotyping of variants and dynamic system improvement.

Psychosocial problems in women attending French, German and Spanish genetics clinics before and after targeted or multigene testing results: an observational prospective study.

OBJECTIVES AND SETTING: Advances in multigene panel testing for cancer susceptibility has increased the complexity of counselling, requiring particular attention to counselees' psychosocial needs. Changes in psychosocial problems before and after genetic testing were prospectively compared between genetic test results in women tested for breast or ovarian cancer genetic susceptibility in French, German and Spanish clinics. PARTICIPANTS AND MEASURES: Among 752 counselees consecutively approached, 646 (86%) were assessed after the initial genetic consultation (T1), including 510 (68%) affected with breast cancer, of which 460 (61%) were assessed again after receiving the test result (T2), using questionnaires addressing genetic-specific psychosocial problems (Psychosocial Aspects of Hereditary Cancer (PAHC)-six scales). Sociodemographic and clinical data were also collected. RESULTS: Seventy-nine (17.2%), 19 (4.1%), 259 (56.3%), 44 (9.6%) and 59 (12.8%) women received a BRCA1/2, another high/moderate-risk pathogenic variant (PV), negative uninformative, true negative (TN) or variant of uncertain significance result (VUS), respectively. On multiple regression analyses, compared with women receiving another result, those with a VUS decreased more in psychosocial problems related to hereditary predisposition (eg, coping with the test result) (ß=-0.11, p<0.05) and familial/social issues (eg, risk communication) (ß=-0.13, p<0.05), almost independently from their problems before testing. Women with a PV presented no change in hereditary predisposition problems and, so as women with a TN result, a non-significant increase in familial/social issues. Other PAHC scales (ie, emotions, familial cancer, personal cancer and children-related issues) were not affected by genetic testing. CONCLUSIONS: In women tested for breast or ovarian cancer genetic risk in European genetics clinics, psychosocial problems were mostly unaffected by genetic testing. Apart from women receiving a VUS result, those with another test result presented unchanged needs in counselling in particular about hereditary predisposition and familial/social issues.

Context and Applications of Targeted Genetic Testing, with Emphasis on Copy Number Variants.

There has been a huge acceleration in our technical ability to detect variation in the human genome in recent years, and there has been a corresponding effort in clinical diagnostic laboratories to take advantage of this progress for the benefit of patients. There has, however, not been an equivalent increase in our understanding of human genetics and disease, not for lack of effort but due to the far greater complexity of understanding variation than the difficulties of detecting it. This chapter describes how software tools can be used to target clinical genetic diagnostic testing in order to exploit technical and scientific advances both efficiently and cost-effectively, while maximizing clinical utility.