scholarly journals Using a dual antibody point-of-care test with visual and digital reads to diagnose syphilis among people living with HIV in Botswana

2021 ◽  
pp. 095646242097563
Author(s):  
Irfaan Maan ◽  
David S Lawrence ◽  
Nametso Tlhako ◽  
Kehumile Ramontshonyana ◽  
Aamirah Mussa ◽  
...  

Syphilis data from low- and middle-income countries are lacking due to limited testing. Point-of-care tests (POCTs) have been promoted to expand testing but previously only included treponemal tests, which cannot distinguish active from past infection. We aimed to assess the feasibility of using a combined treponemal and non-treponemal POCT in HIV clinic patients in Gaborone, Botswana, and estimate syphilis prevalence in our clinic sample using this approach. We recruited 390 non-pregnant patients. Participants underwent a combined treponemal and non-treponemal POCT (Dual Path Platform (DPP®) Syphilis Screen and Confirm Assay (Chembio Diagnostic Systems)) on finger-prick blood sample and a questionnaire. Median age 45 years, 30% men, median CD4 count 565 cells/μL, and 91% had an HIV viral load <400 copies/mL. Five participants had active syphilis (1.3%, 95% CI 0.5–3.0%) and 64 had previous syphilis (16.4%, 95% CI 13.0–20.4%) using the DPP POCT. There was a reasonable level of agreement between digital and visual reading of the POCT (kappa statistic of 0.81); however, visual reading missed three active infections (60%). The level of active syphilis was similar to local antenatal data. The DPP POCT led to five participants with active syphilis being diagnosed and starting same-day treatment. The digital reader should be used.

2022 ◽  
Author(s):  
Benjamin P. Sullivan ◽  
Yu-Shan Chou ◽  
Andrew T. Bender ◽  
Coleman D. Martin ◽  
Zoe G. Kaputa ◽  
...  

Quantitative nucleic acid amplification tests (qNAATs) are critical in treating infectious diseases, such as in HIV viral load monitoring or SARS-CoV-2 testing, in which viral load indicates viral suppression or infectivity. Quantitative PCR is the gold standard tool for qNAATs; however, there is a need to develop point-of-care (POC) qNAATs to manage infectious diseases in outpatient clinics, low- and middle-income countries, and the home. Isothermal amplification methods are an emerging tool for POC NAATs as an alternative to traditional PCR-based workflows. Previous works have focused on relating isothermal amplification bulk fluorescence signals to input copies of target nucleic acids for sample quantification with limited success. In this work, we show that recombinase polymerase amplification (RPA) reactions on paper membranes exhibit discrete fluorescent amplification nucleation sites. We demonstrate that the number of nucleation sites can be used to quantify HIV-1 DNA and RNA in less than 20 minutes. An image-analysis algorithm quantifies nucleation sites and determines the input nucleic acid copies in the range of 67-3,000 copies per reaction. We demonstrate a mobile phone-based system for image capture and onboard processing, illustrating that this method may be used at the point-of-care for qNAATs with minimal instrumentation.


2021 ◽  
Author(s):  
Harriet D Gliddon ◽  
Rachel A McKendry ◽  
Jo Gibbs

AbstractBackgroundHIV viral load (VL) is key to monitoring response to antiretroviral therapy. A number of point-of-care HIV VL tests are in development. These tests could be repurposed for HIV VL self-testing.MethodsWe held a patient and public involvement (PPI) consultation for people living with HIV to explore the prospect of HIV viral load self-testing. We conducted a thematic analysis on the data from this consultation.ResultsKey themes were access, convenience, usability, technical aspects, technology potential, connectivity and confidentiality. Attendees expressed significant appetite for decentralised HIV care, including HIV VL self-testing.ConclusionsThis PPI consultation can help researchers developing HIV viral load self-testing technology to better understand the needs of potential end users. Our findings will help guide the development and implementation of HIV VL self-testing.


Author(s):  
Tobias Broger ◽  
Bianca Sossen ◽  
Elloise du Toit ◽  
Andrew D. Kerkhoff ◽  
Charlotte Schutz ◽  
...  

Author(s):  
Jennifer E.  Iudicello ◽  
Erin E. Morgan ◽  
Mariam A. Hussain ◽  
Caitlin Wei-Ming Watson ◽  
Robert K. Heaton

Human immunodeficiency virus enters the central nervous system (CNS) early after systemic infection, and may cause neural injury and associated neurocognitive impairment through multiple direct and indirect mechanisms. An international conference of multidisciplinary neuroAIDS experts convened in 2005 to propose operationalized research criteria for HIV-related cognitive and everyday functioning impairments. The resulting classification system, known as the Frascati criteria, defined three types of HIV-associated neurocognitive disorder (HAND): asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia (HAD). Consideration of comorbid conditions that can influence neurocognitive performance, such as developmental disabilities, non-HIV forms of CNS compromise (neurological and systemic), severe psychiatric conditions, and substance use disorders, is essential to differential diagnosis. Since the introduction of combination antiretroviral therapy (ART), rates of severe HAND (i.e., HAD) have greatly declined, although the milder forms of HAND remain quite prevalent, even in virally suppressed people living with HIV (PLWH). Beyond ART, clinical management of HAND includes behavioral interventions focused on neurocognitive and functional improvements. This chapter covers a range of HAND-related topics, such as the neuropathological mechanisms of HIV-related CNS injury, assessment and diagnostic systems for neurocognitive and everyday functioning impairment in HIV, treatment and protective factors, aging with HIV, HAND in international settings, and ongoing challenges and controversies in the field. Future needs for progress with HAND include advances in early detection of mild cognitive deficits and associated functional impairment in PLWH; biomarkers that may be sensitive to its underlying pathogenesis; and differential diagnosis of HAND versus age-related, non-HIV-associated disorders.


Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1352
Author(s):  
Darius Riziki Martin ◽  
Nicole Remaliah Sibuyi ◽  
Phumuzile Dube ◽  
Adewale Oluwaseun Fadaka ◽  
Ruben Cloete ◽  
...  

The transmission of Tuberculosis (TB) is very rapid and the burden it places on health care systems is felt globally. The effective management and prevention of this disease requires that it is detected early. Current TB diagnostic approaches, such as the culture, sputum smear, skin tuberculin, and molecular tests are time-consuming, and some are unaffordable for low-income countries. Rapid tests for disease biomarker detection are mostly based on immunological assays that use antibodies which are costly to produce, have low sensitivity and stability. Aptamers can replace antibodies in these diagnostic tests for the development of new rapid tests that are more cost effective; more stable at high temperatures and therefore have a better shelf life; do not have batch-to-batch variations, and thus more consistently bind to a specific target with similar or higher specificity and selectivity and are therefore more reliable. Advancements in TB research, in particular the application of proteomics to identify TB specific biomarkers, led to the identification of a number of biomarker proteins, that can be used to develop aptamer-based diagnostic assays able to screen individuals at the point-of-care (POC) more efficiently in resource-limited settings.


Retrovirology ◽  
2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Catherine M. Moore ◽  
Melanie Grandits ◽  
Clemens Grünwald-Gruber ◽  
Friedrich Altmann ◽  
Maria Kotouckova ◽  
...  

Abstract Background HIV remains one of the most important health issues worldwide, with almost 40 million people living with HIV. Although patients develop antibodies against the virus, its high mutation rate allows evasion of immune responses. Some patients, however, produce antibodies that are able to bind to, and neutralise different strains of HIV. One such ‘broadly neutralising’ antibody is ‘N6’. Identified in 2016, N6 can neutralise 98% of HIV-1 isolates with a median IC50 of 0.066 µg/mL. This neutralisation breadth makes N6 a very promising therapeutic candidate. Results N6 was expressed in a glycoengineered line of N. benthamiana plants (pN6) and compared to the mammalian cell-expressed equivalent (mN6). Expression at 49 mg/kg (fresh leaf tissue) was achieved in plants, although extraction and purification are more challenging than for most plant-expressed antibodies. N-glycoanalysis demonstrated the absence of xylosylation and a reduction in α(1,3)-fucosylation that are typically found in plant glycoproteins. The N6 light chain contains a potential N-glycosylation site, which was modified and displayed more α(1,3)-fucose than the heavy chain. The binding kinetics of pN6 and mN6, measured by surface plasmon resonance, were similar for HIV gp120. pN6 had a tenfold higher affinity for FcγRIIIa, which was reflected in an antibody-dependent cellular cytotoxicity assay, where pN6 induced a more potent response from effector cells than that of mN6. pN6 demonstrated the same potency and breadth of neutralisation as mN6, against a panel of HIV strains. Conclusions The successful expression of N6 in tobacco supports the prospect of developing a low-cost, low-tech production platform for a monoclonal antibody cocktail to control HIV in low-to middle income countries. Graphic abstract


2021 ◽  
Vol 32 (5) ◽  
pp. 435-443
Author(s):  
Maria Elena Ceballos ◽  
Patricio Ross ◽  
Martin Lasso ◽  
Isabel Dominguez ◽  
Marcela Puente ◽  
...  

In this prospective, multicentric, observational study, we describe the clinical characteristics and outcomes of people living with HIV (PLHIV) requiring hospitalization due to COVID-19 in Chile and compare them with Chilean general population admitted with SARS-CoV-2. Consecutive PLHIV admitted with COVID-19 in 23 hospitals, between 16 April and 23 June 2020, were included. Data of a temporally matched-hospitalized general population were used to compare demography, comorbidities, COVID-19 symptoms, and major outcomes. In total, 36 PLHIV subjects were enrolled; 92% were male and mean age was 44 years. Most patients (83%) were on antiretroviral therapy; mean CD4 count was 557 cells/mm3. Suppressed HIV viremia was found in 68% and 56% had, at least, one comorbidity. Severe COVID-19 occurred in 44.4%, intensive care was required in 22.2%, and five patients died (13.9%). No differences were seen between recovered and deceased patients in CD4 count, HIV viral load, or time since HIV diagnosis. Hypertension and cardiovascular disease were associated with a higher risk of death ( p = 0.02 and 0.006, respectively). Compared with general population, the HIV cohort had significantly more men (OR 0.15; IC 95% 0.07–0.31) and younger age (OR 8.68; IC 95% 2.66–28.31). In PLHIV, we found more intensive care unit admission (OR 2.31; IC 95% 1.05–5.07) but no differences in the need for mechanical ventilation or death. In this cohort of PLHIV hospitalized with COVID-19, hypertension and cardiovascular comorbidities, but not current HIV viro-immunologic status, were the most important risk factors for mortality. No differences were found between PLHIV and general population in the need for mechanical ventilation and death.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S496-S497
Author(s):  
Roukaya Al Hammoud ◽  
Elizabeth R Unger ◽  
Gitika Panicker ◽  
Gabriela P Del Bianco ◽  
Gloria Heresi ◽  
...  

Abstract Background Immune dysfunction related to HIV infection is associated with an inability to clear HPV infection and may compromise the immunogenicity of quadrivalent HPV vaccine Gardasil® (4v HPV). Methods Between 2005 and 2017, males and females 7 to 20 years old age, were offered 3-dose 4v HPV vaccine. Plasma IgG titers to HPV 6 (H6), 11 (H11), 16 (H16) and 18 (H18) were measured using multiplex VLP-based ELISA. For the 36 patients, median interval from 1st dose to 2nd and 3rd doses were 73 and 216 days. Plasma sample 1 was collected at median of 91 days after dose 1, sample 2, 169 and sample 3, 740 after respective vaccine doses. A 4th sample was available for 26 patients, median 2327 days after dose 1. Rank-sum test, Χ 2 or Fisher’s Exact Test were employed. Results Before vaccination, 10 (28%) were seropositive to 1 or more HPV types. The baseline seropositives were older than seronegatives (16 years vs 11; p=0.007). After dose 3 all participants had an Ab response to at least 1 HPV type and 32 (89%) were seropositive for 4 HPV types. Seroconversions were H18, 87%; H16 97%; H11, 100%; H6, 97%. Seroconversions after 1 dose of 4v HPV among the baseline seronegatives were 61%, 90%, 86% and 86%, respectively and 22 became seropositive for all 4 types. The 4 baseline seronegative PLWH with partial seroconversion had higher median HIV viral load (VL) compared to baseline seronegative group with full seroconversion (12,920 vs 101 copies/ml; p = 0.052), but had comparable CD4 counts. The rate of post vaccination seropositivity and baseline to peak titer response for each HPV type was not significantly different for baseline sero-groups. Among baseline seronegative, all 19 sampled distant from vaccination remained seropositive to at least 1 HPV type (84% to 3 or more types) and 6 (32%) became seronegative (sero-reversion). Those showing sero-reversion had higher VL compared to the 14 who remained seropositive (9100 vs 48; p =0.015). Time from last dose of 4v HPV to sample 4, CD4%, age, gender, and race/ethnicity were similar between the groups. Bar Graphs representing Ab response to the 4 HPV types following each dose of 4v HPV vaccine Conclusion In the complex environment of a pediatric HIV specialty clinic, most PLWH mounted Ab responses to 4v HPV that were durable. H18 was least immunogenic. Patients with higher HIV VL were less likely to seroconvert for all types and were more likely to sero-revert. Disclosures All Authors: No reported disclosures


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