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Challenges and Opportunities in AIDS

Challenges and Opportunities in AIDS

Sigelman, C. K. (2022)


Despite the importance for their health and well-being of children’s acquiring knowledge and understanding of disease, surprisingly little work has been done to compare children’s thinking about different diseases at different ages to determine whether and how thinking about familiar diseases shapes thinking about newly encountered diseases. The present study reports a new analysis of interviews with 156 children that were conducted in 1992, when AIDS represented a new and life-threatening but not well understood health threat.  The aim was to compare thinking about the causality of a familiar disease, influenza, and a then-unfamiliar disease, AIDS, among third, fifth, and seventh graders. Comparisons of the two diseases and three grade levels focused on: (a) level of understanding based on cognitive-developmental theory and (b) three features defining children’s intuitive theories of disease (a biological ontology or vocabulary, causal propositions featuring an invisible germ or virus, and logical coherence). Scores on all four resulting summary measures and on all but one of eight causal propositions collectively constituting a scientific explanation of each disease, increased with age, with growth especially pronounced from third grade to fifth and seventh grades. Summary scores were moderately intercorrelated, both within each disease and across the two diseases. Folk beliefs about cold weather causing flu and casual contact causing AIDS declined with age. Levels of knowledge and understanding of the two diseases were more often similar than different. However, children’s thinking about flu was ahead of their thinking about AIDS in some respects, especially among the youngest children and especially with respect to symptomology. At the same time, exposure to information during the AIDS epidemic appeared to enable children describing AIDS causality to replace the generic term germ used for flu with the more specific term virus and to better understand that a person must have a disease or its pathogen to transmit it, that the causal agent for a disease is disease-specific, and that the body resists germs and viruses. Implications for better understanding the development of disease concepts and filling gaps in children’s knowledge and understanding in the era of COVID-19 are discussed.

Katbi, M., Fom, T., Adedoyin, A., Klindera, K., Asaolu, O., Magaji, D., Agweye, A., & Faturiyele, I. (2023c)


Background: Pre-exposure prophylaxis (PrEP) is recommended for people at substantial risk of acquiring HIV to prevent new infections. The Nigeria PEPFAR program through USAID funded the implementation of PrEP for Key Population (KP) groups including Men Who Have Sex with Men (MSM), People who inject drugs (PWIDS), and Female sex Workers (FSW) in July 2020. We assessed the number of new infections averted and the financial resources saved because of this intervention.

Methodology: HIV-negative clients from the key population community in North- East Nigeria eligible for PrEP were enrolled over a 7-month period (July 2020 – February 2021). Eligibility criteria used include being at substantial risk for HIV infection based on a screening test administered. The person-month was calculated by using the duration the participants were retained on PrEP. The incidence 15.4/100 person-years of HIV among MSM at high risk of HIV infection in the TRUST study conducted in Nigeria was used to calculate the expected positive cases if PrEP was not provided for those enrolled using the formula (15.4/100 * X) where X is number of person-years. We compared the expected positive to the actual positive seen among KPs while on PrEP within the study period. The cost-effectiveness of being on PrEP was calculated by multiplying the standard cost per HIV infection averted ($13, 267 per HIV infection averted) by the No of HIV averted.

Results: We enrolled a total of 1,197 eligible HIV-negative KPs within the study period (189 were retained for seven months, 407 for four months, 585 for 3 months, and 18 for 1 month). A total of 4722 person-months (394 person-years) were accumulated over the period of the study. Using the incidence of 15.4/100 person-years, the expected positive cases if PrEP was not provided was 61 (15.4/100 *394). With the use PrEP, no client seroconverted to be HIV positive. This means that within the 7-month period, 61 HIV infections were averted. At the cost of $13,267 per HIV infection averted for PrEP, the project saved $809,287 for averting 61 HIV infections in seven months of using PrEP among HIV-negative KPs involved in high-risk behaviors.

Conclusion: This study shows that PrEP is effective in averting new infections among key population groups. Placing high-risk groups such as KPs on PrEP is cost-effective due to the money saved from new infections averted. Increased funding for proven and innovative strategies on PrEP enrolment, retention, and adherence of eligible clients should be expanded for KPs.

De Oliveira, D. C., Cecilio, H., Apostolidis, T., Da Costa, T. R., Hipólito, R., De Oliveira, D., Domingues, J. O., Stefaisk, R., Machado, Y., Gomes, A. M. T., & Marques, S. C. (2022c)


Background: Time perspective can be an important variable for the understanding the quality of life of people living with HIV/AIDS.

Aims: The objective was to examine the relation between quality of life and time perspective among persons living with HIV receiving care from public health services in Brazil.

Methods: Data were collected at four public health services in Brazil. Hierarchical regression analyses were then performed for each of six quality of life domains.

Results: The subscales associated with high quality of life in physical and level of independence domains were low past-negative and high future orientation; psychological and environmental domains were low past-negative, high past-positive and high future orientations; social relations domain were high past-positive and high future orientations; and spirituality, religion and personal beliefs domain was low past-negative orientation.

Conclusion: The hypothesis that time constructs have implications for the experience of the disease and for evaluation of quality of life was proven determined by positive orientations like future and past-positive and past-negative orientation.

Lisziewicz, R., Oviedo, F., Szász, A., Ferres, J. L., Lori, F., & Lisziewicz, J. (2023b)


Background: The COVID-19 pandemic has necessitated the development of efficient diagnostic tools to predict T-cell responses, which are crucial for viral clearance and protection against reinfection. Current diagnostic tests lack the ability to predict the epitope repertoire of an individual that induces T-cell responses.

Methods: We developed VERDI, a new machine learning-based diagnostic tool that leverages the sequence data of all the six HLA class I alleles of an individual to rank all putative epitopes based on their potential to induce T-cell responses. VERDI was trained on a comprehensive clinical dataset of 920 SARS-CoV-2 epitopes and validated using an independent dataset collected for the FDA-approved T-detect COVID test. We compared VERDI’s performance with existing HLA-allele-based models through statistical analyses.

Results: Our findings reveal that VERDI’s top-ranked epitopes accurately represent the individual’s epitope repertoire that participates in T-cell responses. VERDI outperformed current models, improving T-cell response prediction recall by threefold and precision by eightfold. It exhibited exceptional diagnostic accuracy, precision, and recall in predicting the potency of the top 20 epitopes. Despite experimental limitations that allow testing of only 1% of putative epitopes, VERDI accurately predicted 30% of these, implying a potentially higher accuracy if broader testing were feasible. Notably, the mean potency of the top-ranked epitopes predicted by VERDI, which reflects the strength of an individual’s SARS-CoV-2-specific T-cell responses, exhibited a Gaussian distribution.

Conclusions: VERDI is the first diagnostic tool that uses the complete HLA genotype data to predict the breadth and strength of an individual’s T-cell responses to SARS-CoV-2 infection. Its ability to accurately identify the potency of epitopes involved in individual T-cell responses and its superior performance compared to the state-of-the-art make it a new resource for personalized vaccine design and disease management.

Urada, L. A., McClung, M., Brocklin, R., & Blumenthal, J. (2022d)


Background: Peer navigation is an evidence-based model for engaging and retaining women living with HIV in medical care. Participants of an adapted Lotus peer navigation group intervention were hypothesized to have more self-perceived HIV self-care and advocacy behaviors following their participation than non-Lotus participants at an agency serving cisgender women and their families affected by HIV in San Diego, California.

Methods: The peer navigation intervention, Lotus, was adapted to include new modules on substance use, human trafficking, and intimate partner violence and piloted to compare its overall effects with a comparison group (2018-2019). Ninety-five cisgender women living with HIV (WLWH) completed posttest surveys measuring their perceived changes in peer advocacy and self-advocacy following their participation in a pilot of an adapted Lotus. Participants of the four-session Lotus group intervention (n=34) were compared to non-Lotus participants who engaged in other types of group activities at the agency (n=61). The Lotus group participants included a cohort of cisgender women > 50 years old, English and Spanish speaking women, and a mixed age and race/ethnicity group. All clients of Christie’s Place, an organization for women living with HIV in San Diego, were eligible if they were not actively using illicit substances substances in the past year. Cross-sectional bivariate analyses were run to determine differences between intervention and comparison groups. The groups were not randomized.

Results: Among 95 participants, 17% were White, 14% Black/African American, 44% Hispanic/Latino, and 25% Other/Mixed race/ethnicity with median age 51 years (IQR: 45-60). Eleven Latina, 9 White, 6 Black/African American, and 8 Other/Mixed individuals participated in Lotus. In bivariate analyses, Lotus WLWH living with HIV at posttest took their HIV medications correctly (p=0.040) and attended their healthcare/other service appointments as advised/scheduled 3 times more often than non-Lotus WLWH (p=0.014). They advocated for themselves within medical and social service settings 6 times more often (p<0.001) and talked openly with their doctor 4 times more often (p=0.028). They were also twice as likely to talk more often with their partner about safer sex (p=0.022) and PrEP (p=0.037) and a peer about safer sex (p=0.001). They were 3 times more likely to help a peer understand how HIV medications can improve their health (p=0.001). Medical records showed all Lotus intervention participants as virally suppressed one year after their participation.

Conclusions: Participants of an HIV peer navigation intervention experienced significant changes in self-reported self-advocacy outcomes. Peer navigation training interventions remain critical for medication adherence and self-advocacy among cisgender WLWH.

Arnold, R., Bausek, N., Gaskill, C. S., & Midani, T. (2023)


Background: Dysarthria frequently occurs as a result of stroke and adversely impacts speech sound production, making it more difficult for the listener to understand what the person with dysarthria is attempting to communicate. This in turn may lead to social isolation, depression, and increased cost of care. Some studies have underscored the importance of respiratory muscle strengthening as it relates to improvement of speech intelligibility. This retrospective investigation examined the effects of a combined Respiratory Muscle Training (cRMT) protocol upon speech intelligibility in persons post single cerebrovascular accident (CVA).

Methods: The clinical data of 10 patients who requested pro bono speech therapy for the diagnosis and treatment of dysarthria following a single stroke was utilized for this study. The intervention group was treated with three 5-minute sessions with cRMT each day for 28 consecutive days. The control group received no cRMT and no other therapeutic exercise intervention during the time period. Respiratory and speech intelligibility were assessed pre- and post-intervention in terms of peak expiratory flow, subject self-perception of intelligibility, and word level intelligibility.

Results: After 28 days of cRMT, the intervention group (IG) exhibited significant gains compared to the control group (CG) in peak expiratory flow (PEF) (IG: 73.12% vs CG: 4.66%), Self-Perception of Intelligibility (IG: 72.38% vs CG: 0.83%), and the word task of the Assessment of Intelligibility of Dysarthric Speech (AIDS) (IG: 43.92% vs. CG: 0%). 

Conclusion: These data suggest cRMT is a feasible and effective treatment for improving breath support and speech intelligibility in persons with dysarthric speech.

Figueiredo, I., Martins, M., Midões, C., & Ferrão, J. (2022c)


Opportunistic infections affect patients with immunocompromised status and are caused by common microorganisms with more severe presentations, or atypical organisms that do not cause disease in the immunocompetent. The type of infection varies with the type of immune dysfunction.

Patients with cell-mediated immune dysfunction tend to be infected with a range of viral infections, intracellular bacteria, and fungi. This contrasts to patients with defects in humoral immunity, where infections with encapsulated bacteria, and enteric organisms such Giardia lamblia and enteroviruses predominate. Patients with phagocytic defects are especially prone to infections with Gram-negative bacteria and fungi, whilst those with complement disorders are prone to recurrent infections with encapsulated bacteria. In contrast to patients with primary immunodeficiencies, which usually present with only one defect of the above, acquired immunodeficiencies present with a variety of those, and clinical presentations are diversified.

The epidemic of HIV and AIDS shed some light into infections that were before extremely rare, by making them frequent, but with the advent of anti-retroviral therapy their clinical presentation has shifted. Also, the emergence of novel immunotherapies for cancer and autoimmune diseases, allied with an increase in organ transplant has increased the pool of immunosuppressed patients without HIV, which present differently regarding opportunist infections.

Rapid and specific microbiologic diagnosis is essential. Newer microbiologic assays have improved the diagnosis and management of opportunistic infections.

Our aim was to revise and summarize the most frequent opportunist infections, and how their presentation and course compares in different immunosuppressed diseases (HIV and non-HIV).

Chua, N., John, T., & Buchser, E. (2023)


Lumbar epidural spinal cord stimulation (SCS) was used to improve motor function in a 50-yr old patient who suffered hemiparesis due to a basal ganglia haemorrhagic stroke.  Spinal cord stimulation targeted at the dorsal root afferent fibres at the conus improved the tonic control of the muscles at the knee and ankle joints. This allowed the patient better left knee and foot motor control. The improvement was documented initially during ambulation on a treadmill using decreasing body weight support and subsequently when using walking aids. Our observation is consistent with previous human data suggesting that in humans with brain lesions, the stimulation of preserved neural circuitry can increase spontaneous muscle tone in affected muscles and improve locomotion.

Cockerham, C. (2024)


Patients presenting with neuro-ophthalmic disorders pose a diagnostic challenge when they present to community hospital emergency departments (ED) where expertise in neuro-ophthalmology is often limited. Many have no ophthalmology coverage or have a call group composed of general ophthalmologists who are not comfortable managing neuro-ophthalmic disorders. The limited familiarity with neuro-ophthalmology and the lack of essential equipment, such as a fundus camera or optical coherence tomography (OCT), contribute to a substantial gap in accurate and timely diagnosis and treatment. This deficiency results in patients making multiple visits to the emergency department, where they receive limited or no treatment, and this overall increases the risk of disease progression and potentially blindness.

Advocating for standardized protocols and integrating technological advancements will aid non-ophthalmologist physicians and mid-level physician extenders in the initial assessment and management of patients with acute visual issues. Additionally, improving the accessibility of neuro-ophthalmological services through telehealth, and diagnostic aids (such as smartphone-based fundus cameras) in emergency department settings is essential to avoid overlooked or misdiagnosed neuro-ophthalmological disorders.

We describe two common scenarios that illustrate the diagnostic journey of patients. One is a young patient presenting with headache and vague visual symptoms and the other is an elderly patient with unilateral visual loss and vague headaches. We will focus on the crucial role of the fundus camera/OCT in identifying disc edema but also discuss the key questions that help guide diagnosis.

Panagopoulos, D., Strantzalis, G., Gavra, M., Korfias, S., & Karydakis, P. (2022)


In an effort to maximize extent of resection (EOR) regarding gliomas, intraoperative MRI (i-MRI) and 5-aminolevulinic acid (5-ALA) have been developed. Our study aimed to investigate the comparative contribution of 5-aminolevulinic acid and i-MRI in maximizing EOR in gliomas.

We searched the PubMed and ScienceDirect services for randomized controlled trials, controlled trials and interrupted time series studies evaluating the effect of i-MRI on gross total resection (GTR) rates and on overall survival in glioma patients. Our primary study endpoint was the definition of the percentage of patients who were offered GTR. Other relevant points of interest included the determination of overall and progression-free survival and subgroup analyses for level of evidence.

I-MRI aids in achieving GTR (odds ratio 2.71, p<0.0001). Magnet field strength does not affect significantly either GTR rates (p=0.08). The cost of the procedure is dependent on the workload of the i-MRI system. These data suggest that i-MRI or 5-ALA improves progression-free and overall survival, although there are several restrictions related to their effectiveness and reliability.

 I-MRI and 5-ALA are considered to be effective adjuncts in the achievement of GTR of gliomas. When these methods are compared, there is no definite conclusion regarding which method is more effective.

Humphries, T., Mathur, G., Napoli, D. J., & Rathmann, C. (2023)


Sign languages are complex and intact human languages essential to the development and health of deaf children and adults. Yet, still, many families and medical professionals think the optimal option for deaf children is to be raised with spoken language, usually including a cochlear implant. Cochlear implants, however, have variable outcomes with language acquisition. Medical professionals, especially pediatricians, need to update their knowledge and understanding of best practices to ensure they more appropriately support families to protect the overall health of their deaf child. The child who does not have a firm first language foundation is at risk of poor (neuro-) cognitive, psycho-social, and socio-emotional development. Developmental delays and life-long, irreparable damages can and should be prevented. Ultimately, securing a firm first language foundation is a matter of health. It is essential to back away from the concept of one-choice-fits-all and, instead, begin with exposing the deaf child to a visually accessible sign language in a multimodal and multilingual environment as soon as it is known that the child is deaf. With a sign language as the linguistic foundation, other practices automatically make more sense –including hearing aids and/or cochlear implants – and those other practices have a greater chance of success, even the development of spoken language(s) (including speech) and written language(s), which has been shown to be supported by the presence of visually accessible sign language(s) in the child’s environment.

In order to aid pediatricians in advising parents, we have prepared a list of factors on which families of deaf newborns or newly-deafened young children need guidance, complete with discussion and citations of relevant recent work. We have been working as a team in this area for the past dozen years. Thus, we also list our publications. The goal here is to ensure deaf individuals’ right to inclusion in society in terms of education, employment, health, cultural life and all other aspects of being human and of societal participation. The use of a sign language(s) allows deaf people to be included; the preclusion of a sign language carries the risk of low quality of life and of language deprivation.

Dasari, V., Bolimera, P., Shukla, S., Ganar, R., Elwell, T., Goyal, R., & Dravida, S. (2023)


Polyvalent antivenom potency tested for every batch and at four different stages of production is a regulatory requirement to be followed by the industry. Antivenom manufacturers have been following the gold standard test methodology for estimating median effective dose in mice for ages. Here, we report a non-animal New Approach Methodology that aligns with 3Rs in animal testing agenda, leveraging in vitro human stem cell technology for recreating microphysiological system complemented with process automation, Artificial Intelligence and Machine Learning digital workers’ effective utilization in the assay system to measure Naja naja snake antivenom potency.  In vitro neutralization performed on specially configured human Microphysiological System acquired phenotype data sets at 20X magnification were analyzed against benchmark panels in the trained prediction model while the Artificial Intelligence predicted median effective dose value of venom-antivenom mixture was 3.9μL, showing a potency value of 2.04 mg recorded as the readout. This method adopted in the antivenom producer’s workflow will reduce reliance on mice-based testing and showcases potential for acceptance of robust alternative strategy to traditionally practiced protocols.

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