Implementing community-based Dried Blood Spot (DBS) testing for HIV and hepatitis C: a qualitative analysis of key facilitators and ongoing challenges.

BACKGROUND: In 2018, the Community-Based Research Centre (CBRC) invited gay, bisexual, trans, queer men and Two-Spirit and non-binary people (GBT2Q) at Pride Festivals across Canada to complete in-person Sex Now surveys and provide optional dried blood spot (DBS) samples screening for human immunodeficiency virus (HIV) and hepatitis C virus (HCV). As there is a lack of research evaluating the implementation of DBS sampling for GBT2Q in community settings, we aimed to evaluate this intervention, identifying key facilitators and ongoing challenges to implementing community-based DBS screening for HIV/HCV among GBT2Q. METHODS: We conducted sixteen one-on-one interviews with individuals involved with the community-based DBS collection protocol, including research staff, site coordinators, and volunteer DBS collectors. Most individuals involved with DBS collection were "peers" (GBT2Q-identified). The Consolidated Framework for Implementation Research (CFIR) guided our data collection and analysis. RESULTS: Interviewees felt that DBS collection was a low-barrier, cost-effective, and simple way for peers to quickly screen a large number of Sex Now respondents. Interviewees also noted that the community and peer-based aspects of the research helped drive recruitment of Sex Now respondents. Most interviewees felt that the provision of results took too long, and that some Sex Now respondents would have preferred to receive their test results immediately (e.g., rapid or point-of-care testing). CONCLUSION: Peer-based DBS sampling can be an effective and relatively simple way to screen GBT2Q at Pride Festivals for more than one sexually transmitted and blood borne infection.

Estimating nutritional needs in paediatric heart failure: beyond the equations.

BACKGROUND: Nutrition optimisation is imperative in paediatric patients with heart failure. Energy needs can be assessed using indirect calorimetry. METHODS: Presented are two cases of children with clinical heart failure who benefited from indirect calorimetry. RESULTS: Using indirect calorimetry, it was determined both cases were hypermetabolic. CONCLUSION: These cases demonstrate the impact of heart failure on metabolic rate and growth. Energy requirements were up to two times higher than estimations from predictive equations.

Clinical Correlates of Human Immunodeficiency Virus-1 (HIV-1) DNA and Inducible HIV-1 RNA Reservoirs in Peripheral Blood in Children With Perinatally Acquired HIV-1 Infection With Sustained Virologic Suppression for at Least 5 Years.

BACKGROUND: The Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) study is a prospective, multicenter, Canadian cohort study investigating human immunodeficiency virus-1 (HIV-1) reservoirs, chronic inflammation, and immune responses in children with perinatally acquired HIV-1 infection. The focus of this report is HIV-1 reservoirs and correlates in the peripheral blood of children who achieved sustained virologic suppression (SVS) for ≥5 years. METHODS: HIV-1 reservoirs were determined by measuring HIV-1 DNA in peripheral blood mononuclear cells and inducible cell-free HIV-1 RNA in CD4+ T-cells by a prostratin analogue stimulation assay. HIV serology was quantified by signal-to-cutoff ratio (S/CO). RESULTS: Of 228 enrolled participants, 69 achieved SVS for ≥5 years. HIV-1 DNA, inducible cell-free HIV-1 RNA, and S/COs correlated directly with the age of effective combination antiretroviral therapy (cART) initiation (P < .001, P = .036, and P < .001, respectively) and age when SVS was achieved (P = .002, P = .038, and P < .001, respectively) and inversely with the proportion of life spent on effective cART (P < .001, P = .01, and P < .001, respectively) and proportion of life spent with SVS (P < .001, P = .079, and P < .001, respectively). Inducible cell-free HIV-1 RNA correlated with HIV-1 DNA, most particularly in children with SVS, without virologic blips, that was achieved with the first cART regimen initiated prior to 6 months of age (rho = 0.74; P = .037) or later (rho = 0.87; P < .001). S/COs correlated with HIV-1 DNA (P = .003), but less so with inducible cell-free HIV-1 RNA (P = .09). CONCLUSIONS: The prostratin analogue stimulation assay, with its lower blood volume requirement, could be a valuable method for evaluating inducible HIV-1 reservoirs in children. Standard commercial HIV serology may be a practical initial indirect measure of reservoir size in the peripheral blood of children with perinatally acquired HIV-1 infection.

Repeated false reactive ADVIA centaur® and bio-rad Geenius™ HIV tests in a patient self-administering anabolic steroids.

BACKGROUND: An individual is considered HIV positive when a confirmatory HIV-1/HIV-2 differentiation test returns positive following an initial reactive antigen/antibody combination screen. Falsely reactive HIV screens have been reported in patients with various concomitant infectious and autoimmune conditions. Falsely positive confirmatory HIV differentiation assays are seen less frequently, but have been observed in cases of pregnancy, pulmonary embolism, and malaria. CASE PRESENTATION: A healthy 27 year-old man was referred after a reactive ADVIA Centaur® HIV Ag/Ab screen and positive Bio-Rad Geenius™ HIV 1/2 Confirmatory assay, suggesting HIV-1 infection. The patient's HIV viral load was undetectable prior to initiation of antiretroviral therapy, and remained undetectable on subsequent testing after initiation of antiretroviral therapy. Both Centaur® and Geenius™ tests were repeated and returned reactive. As this patient was believed to be at low risk of acquiring HIV infection, samples were additionally run on Genscreen™ HIV-1 Ag assay and Fujirebio Inno-LIA™ HIV-1/2 score, with both returning non-reactive. For confirmation, the patient's proviral HIV DNA testing was negative, confirming the initial results as being falsely positive. The patient disclosed that he had been using a variety of anabolic steroids before and during the time of HIV testing. DISCUSSION AND CONCLUSIONS: The erroneous diagnosis of HIV can result in decreased quality of life and adverse effects of antiretroviral therapy if initiated, hence the importance of interpreting the results of HIV testing in the context of an individual patient. This reports suggests a potential association between the use of anabolic steroids and falsely-reactive HIV testing.

Age-related decline and diagnostic performance of more and less prevalent clinical cases.

Since cognitive abilities have been shown to decrease with age, it is expected that older physicians would not perform as well as their younger counterparts on clinical cases unless their expertise can counteract the cognitive effects of aging. However, studies on the topic have shown contradictory results. This study aimed to further investigate the effect of aging on physicians' diagnostic accuracy when diagnosing prevalent and less prevalent cases based on clinical vignettes. A mixed design was used to assess the influence of case prevalence (high vs. low) as a within-subjects factor, and age group as a between subjects factor (<30; n = 23, 30-39; n = 19, 40-49; n = 27, >50 years old; n = 19) on the diagnostic accuracy of 65 family physicians and 25 residents. Repeated Measure ANOVA revealed a significant effect of case prevalence (p < .001) and age group (p < .001). Post-hoc analyses revealed that younger physicians showed the best performance. This study did not demonstrate the positive effect of experience in older physicians. In line with previous studies on expertise development, findings of the present study suggest that skills should be actively maintained to assure a high performance level throughout one's lifespan. If not, performance level could gradually decline with age.

Growth Faltering and Developmental Delay in HIV-Exposed Uninfected Ugandan Infants: A Prospective Cohort Study.

BACKGROUND: HIV-exposed but uninfected (HEU) infants are at increased risk of impaired early linear growth and cognitive development. We examined associations between prenatal and postnatal growth and subsequent neurodevelopment in Ugandan HEU infants, hypothesizing that early insults may explain alterations in both somatic growth and brain development. METHODS: We prospectively followed a cohort of HEU infants from birth to 18 months of age, and measured length/height, weight, head, and arm circumference longitudinally. The Malawi Development Assessment Tool (MDAT, 12 and 18 months) and the Color Object Association Test (18 months) were used for developmental assessments. RESULTS: Among 170 HEU infants, the prevalence of low-birth weight and failure to thrive was 7.6% and 37%, respectively. HEU infants had MDAT scores that were similar to the reference population. The mean (SD) score on the Color Object Association Test was 5.5 (3.1) compared with 6.9 (5.3) in developmentally normal children. Developmental ability at age 18 months showed strong cross-sectional correlation with weight-for-age (ρ = 0.36, P < 0.0001), length/height-for-age (ρ = 0.41, P < 0.0001), head circumference-for-age (ρ = 0.26, P = 0.0011), and mid-upper arm circumference-for-age (ρ = 0.34, P = 0.0014). There was a statistically significant correlation between birth weight and MDAT z-score at 18 months (ρ = 0.20, P = 0.010). Failure to thrive was associated with lower MDAT z-score [median -0.13 (IQR -0.75 to +0.14) versus +0.14 (IQR -0.44 to +0.63), P = 0.042]. CONCLUSION: Growth faltering in HEU infants was associated with lower attainment of developmental milestones at age 18 months. Our findings point to a simple screening method for identifying HEU infants at risk for developmental intervention.

HIV misdiagnosis: A root cause analysis leading to improvements in HIV diagnosis and patient care.

BACKGROUND: Standard diagnostic testing for HIV infection has traditionally relied on a high sensitivity HIV antibody screening test using an enzyme-linked immunosorbent assay (ELISA) followed by a high specificity antibody confirmatory test such as a Western Blot. Recently several of the screening assays have been enhanced with an ability to identify p24 antigen thereby narrowing the diagnostic window. OBJECTIVES: To explore the implications of enhanced HIV screening methods that may be leading to HIV misdiagnoses. STUDY DESIGN: A patient deemed to be an HIV infected 'elite controller' was found to be misdiagnosed when undergoing detailed investigations prior to initiating antiretroviral therapy. A root cause analysis was performed to identify the causative factors of this misdiagnosis. A retrospective review of all "elite controllers" in Alberta, Canada revealed challenges of current HIV testing algorithms. RESULTS: Technical and human factors were identified as being causative in this HIV misdiagnosis including (i) high rates of false reactive results on the Abbott ARCHITECT HIV-1&2 COMBO EIA, (ii) human error in reading the initial Western blot, (iii) HIV algorithmic directives in which confirmatory (Western blot) testing was not performed on a repeatedly reactive screen test. The outcome of this analysis identified opportunities for improvement, including implementation of a newly approved (automated) confirmatory assay and improved communication between the clinician and laboratory. CONCLUSIONS: HIV testing remains problematic despite significant advances in HIV test performance and algorithm development, presenting new and unexpected issues. Ensuring a high-quality management system including implementation of the latest HIV technologies and algorithms along with human resources and policies are required to minimize the impact of false positive diagnoses, especially in the era of universal screening and 'test and treat' recommendations.