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Sexually Transmitted Infections Jun 2024Populations who seek HIV pre-exposure prophylaxis (PrEP) are disproportionately affected by hepatitis A virus (HAV), hepatitis B virus (HBV) and human papillomavirus...
HIV pre-exposure prophylaxis and opportunities for vaccination against hepatitis A virus, hepatitis B virus and human papillomavirus: an analysis of the Ontario PrEP cohort study.
OBJECTIVES
Populations who seek HIV pre-exposure prophylaxis (PrEP) are disproportionately affected by hepatitis A virus (HAV), hepatitis B virus (HBV) and human papillomavirus (HPV). We examined immunity/vaccination against these infections among participants in the Ontario PrEP cohort study (ON-PrEP).
METHODS
ON-PrEP is a prospective cohort of HIV-negative PrEP users from 10 Ontario clinics. We descriptively analysed baseline immunity/vaccination against HAV (IgG reactive), HBV (hepatitis B surface antibody >10) and HPV (self-reported three-dose vaccination). We further performed multivariable logistic regression to identify characteristics associated with baseline immunity/vaccination. We used cumulative incidence functions to describe vaccine uptake among participants non-immune at baseline.
RESULTS
Of 633 eligible participants, 59.1% were white, 85.8% were male and 79.6% were gay. We found baseline evidence of immunity/vaccination against HAV, HBV and HPV in 69.2%, 81.2% and 16.8% of PrEP-experienced participants and 58.9%, 70.3% and 10.4% of PrEP-naïve participants, respectively. Characteristics associated with baseline HAV immunity were greater PrEP duration (adjusted OR (aOR) 1.41/year, 95% CI 1.09 to 1.84), frequent sexually transmitted and bloodborne infection (STBBI) testing (aOR 2.38, 95% CI 1.15 to 4.92) and HBV immunity (aOR 3.53, 95% CI 2.09 to 5.98). Characteristics associated with baseline HBV immunity were living in Toronto (aOR 3.54, 95% CI 1.87 to 6.70) or Ottawa (aOR 2.76, 95% CI 1.41 to 5.40), self-identifying as racialised (aOR 2.23, 95% CI 1.19 to 4.18), greater PrEP duration (aOR 1.39/year, 95% CI 1.02 to 1.90) and HAV immunity (aOR 3.75, 95% CI 2.19 to 6.41). Characteristics associated with baseline HPV vaccination were being aged ≤26 years (aOR 9.28, 95% CI 2.11 to 40.77), annual income between CAD$60 000 and CAD$119 000 (aOR 3.42, 95% CI 1.40 to 8.34), frequent STBBI testing (aOR 7.00, 95% CI 1.38 to 35.46) and HAV immunity (aOR 6.96, 95% CI 2.00 to 24.25). Among those non-immune at baseline, overall cumulative probability of immunity/vaccination was 0.70, 0.60 and 0.53 among PrEP-experienced participants and 0.93, 0.80 and 0.70 among PrEP-naïve participants for HAV, HBV and HPV, respectively.
CONCLUSIONS
Baseline immunity to HAV/HBV was common, and a sizeable proportion of non-immune participants were vaccinated during follow-up. However, HPV vaccination was uncommon. Continued efforts should be made to remove barriers to HPV vaccination such as cost, inclusion in clinical guidelines and provider recommendation.
PubMed: 38914474
DOI: 10.1136/sextrans-2023-055961 -
PLoS Computational Biology Jun 2024Carbohydrates and glycoproteins modulate key biological functions. However, experimental structure determination of sugar polymers is notoriously difficult....
Carbohydrates and glycoproteins modulate key biological functions. However, experimental structure determination of sugar polymers is notoriously difficult. Computational approaches can aid in carbohydrate structure prediction, structure determination, and design. In this work, we developed a glycan-modeling algorithm, GlycanTreeModeler, that computationally builds glycans layer-by-layer, using adaptive kernel density estimates (KDE) of common glycan conformations derived from data in the Protein Data Bank (PDB) and from quantum mechanics (QM) calculations. GlycanTreeModeler was benchmarked on a test set of glycan structures of varying lengths, or "trees". Structures predicted by GlycanTreeModeler agreed with native structures at high accuracy for both de novo modeling and experimental density-guided building. We employed these tools to design de novo glycan trees into a protein nanoparticle vaccine to shield regions of the scaffold from antibody recognition, and experimentally verified shielding. This work will inform glycoprotein model prediction, glycan masking, and further aid computational methods in experimental structure determination and refinement.
PubMed: 38913746
DOI: 10.1371/journal.pcbi.1011895 -
PLoS Medicine Jun 2024Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting...
BACKGROUND
Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. We conducted a multicenter, randomized, partially blinded Phase I clinical trial to evaluate the safety and serum concentrations of VRC07-523LS, administered in multiple doses and routes to healthy adults without HIV.
METHODS AND FINDINGS
Participants were recruited between 2 February 2018 and 9 October 2018. A total of 124 participants were randomized to receive 5 VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), subcutaneous (SC) (T4: 2.5 mg/kg, T5: 5 mg/kg), or intramuscular (IM) (T6: 2.5 mg/kg or P6: placebo) routes at 4-month intervals. Participants and site staff were blinded to VRC07-523LS versus placebo for the IM group, while all other doses and routes were open-label. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum PK. Neutralization activity was measured in a TZM-bl assay and antidrug antibodies (ADAs) were assayed using a tiered bridging assay testing strategy. Injections and infusions were well tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusion reactions reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals [95% CIs]) following the first administration were 29.0 μg/mL (25.2, 33.4), 58.5 μg/mL (49.4, 69.3), and 257.2 μg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 μg/mL (8.8, 13.3) and 22.8 μg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 μg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM (95% CIs) concentrations immediately prior to the second administration were 3.4 μg/mL (2.5, 4.6), 6.5 μg/mL (5.6, 7.5), and 27.2 μg/mL (23.9, 31.0) with IV dosing; 0.97 μg/mL (0.65, 1.4) and 3.1 μg/mL (2.2, 4.3) with SC dosing, and 2.6 μg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titers, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A single participant was found to have low titer ADA at a lone time point. VRC07-523LS has an estimated mean half-life of 42 days across all doses and routes (95% CI: 40.5, 43.5), over twice as long as VRC01 (15 days).
CONCLUSIONS
VRC07-523LS was safe and well tolerated across a range of doses and routes and is a promising long-acting bnAb for inclusion in HIV-1 prevention regimens.
TRIAL REGISTRATION
ClinicalTrials.gov/ NCT03387150 (posted on 21 December 2017).
PubMed: 38913710
DOI: 10.1371/journal.pmed.1004329 -
PloS One 2024HIV/AIDS is a chronic disease that challenges public health worldwide and causes morbidity and mortality in humans. The main purpose of this study was to investigate the...
Determinants of longitudinal changes of CD4 cell count and survival time to death of HIV/AIDS patients treated at Yabelo General Hospital, the case of pastoralist area: Using joint modelling approach.
INTRODUCTION
HIV/AIDS is a chronic disease that challenges public health worldwide and causes morbidity and mortality in humans. The main purpose of this study was to investigate the determinants of longitudinal changes in CD4 cell count and survival time to death among HIV/AIDS patients as adults from January 2016 to December 2019 at Yabelo General Hospital. The intellectual gap in this study was focused on the study area, which means that the study related to joint modeling doesn't exist in the pastoralist community of Borena.
METHODS
This study involved 293 adult HIV-infected adults that could be collected from the recorded patient chart data, and the study design is a retrospective cohort design. The study used a Cox proportional hazard model, a linear mixed effect model, and a joint model, which is the combination of both model processes.
RESULTS
The joint model showed that longitudinal CD4 cell count is significantly associated with survival time (p-value = 0.0253). Covariates such as visiting time, age, weight, educational status, ART adherence, and functional status were statistically significant factors associated with mean changes in the CD4 cell count of HIV patients. WHO stage, educational status, place of residence, TB, family history, and opportunistic infection disease had a significant effect on the survival time of HIV patients.
CONCLUSIONS
The estimated association parameter is a negative value, which indicates both outcomes are negatively associated, and higher values of the CD4 cell count are associated with better survival.
Topics: Humans; Male; CD4 Lymphocyte Count; Female; Adult; HIV Infections; Retrospective Studies; Middle Aged; Hospitals, General; Acquired Immunodeficiency Syndrome; Longitudinal Studies; Proportional Hazards Models
PubMed: 38913649
DOI: 10.1371/journal.pone.0305519 -
JCI Insight May 2024Identifying immune correlates of protection is a major challenge in AIDS vaccine development. Anti-Envelope antibodies have been considered critical for protection...
Identifying immune correlates of protection is a major challenge in AIDS vaccine development. Anti-Envelope antibodies have been considered critical for protection against SIV/HIV (SHIV) acquisition. Here, we evaluated the efficacy of an SHIV vaccine against SIVmac251 challenge, where the role of antibody was excluded, as there was no cross-reactivity between SIV and SHIV envelope antibodies. After 8 low-dose intrarectal challenges with SIVmac251, 12 SHIV-vaccinated animals demonstrated efficacy, compared with 6 naive controls, suggesting protection was achieved in the absence of anti-envelope antibodies. Interestingly, CD8+ T cells (and some NK cells) were not essential for preventing viral acquisition, as none of the CD8-depleted macaques were infected by SIVmac251 challenges. Initial investigation of protective innate immunity revealed that protected animals had elevated pathways related to platelet aggregation/activation and reduced pathways related to interferon and responses to virus. Moreover, higher expression of platelet factor 4 on circulating platelet-leukocyte aggregates was associated with reduced viral acquisition. Our data highlighted the importance of innate immunity, identified mechanisms, and may provide opportunities for novel HIV vaccines or therapeutic strategy development.
Topics: Animals; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; SAIDS Vaccines; Macaca mulatta; Immunity, Innate; CD8-Positive T-Lymphocytes; Antibodies, Viral; Male; Vaccines, Attenuated
PubMed: 38912579
DOI: 10.1172/jci.insight.175800 -
Biomedical Reports Aug 2024Late-stage cancers lack effective treatment, underscoring the need for early diagnosis to improve prognosis and decrease mortality rates. Molecular markers, such as DNA...
Late-stage cancers lack effective treatment, underscoring the need for early diagnosis to improve prognosis and decrease mortality rates. Molecular markers, such as DNA methylation, offer promise in early cancer detection. The present study compared commercial kits for analyzing DNA from cervical liquid cytology samples in cancer screening. Rapid bisulfite conversion kits using silica spin-columns and magnetic beads were assessed against standard DNA extraction and bisulfite conversion methods for profiling DNA methylation using quantitative methylation-specific PCR. amplification indicated the suitability of small sample volumes for methylation studies using either the pellet or supernatant (cell-free DNA) parts. Comparison of Bisulfite Conversion Kit-Whole Cell (Abcam), Methylamp Bisulfite Modification (Epigentek), EpiTect Fast LyseAll Bisulfite Kit (Qiagen GmbH) and EZ DNA Methylation-Direct Kit (Zymo Research Corp.) showed no significant differences in cycle threshold values. EZ-96 DNA Methylation-Lightning MagPrep (Zymo Research Corp.), a hybrid kit in a 96-well plate format, exhibited swift turnaround time and similar amplification efficiency. Automation with magnetic bead kits increased throughput without compromising amplification efficiency in open PCR systems. Cost analysis favored direct kits over the gold standard manual protocol. This comparison aids in selecting cost-effective DNA methylation diagnostic tests. The present study confirmed comparable kit performance in methylation-based analysis, highlighting the adequacy of cytology samples and the potential of bodily fluids as alternatives for liquid biopsy.
PubMed: 38912171
DOI: 10.3892/br.2024.1800 -
Hong Kong Journal of Occupational... Jun 2024The use of walking aids is widely acknowledged as one of the most relied-on forms of assistive technology. Using stick-shaped devices, such as a cane, is often the...
BACKGROUND
The use of walking aids is widely acknowledged as one of the most relied-on forms of assistive technology. Using stick-shaped devices, such as a cane, is often the entrance for many people to the world of assistive technologies, often accompanied by the negative stigma associated with ageing and disability.
OBJECTIVES
This study investigated the perception of disability and needs of the Hong Kong population using walking aids, aiming to inform device design and service provision.
METHODS
We observed 391 individuals using cane-like devices in their natural environment and conducted semi-structured interviews with 28 participants to understand stigma, barriers to acquisition, training, and design requirements.
RESULTS
Half of the interviewees (50%, = 14) did not feel disabled when using a walking stick, while 39% felt slightly disabled. 56% of the observed sample used non-medical-looking aids like hiking poles or umbrellas. Most interviewees (79%) purchased off-the-shelf devices, but less than half received seller support in choosing appropriate aids.
CONCLUSION
The feelings associated with using walking sticks and similar devices are mostly positive. There is a preference in Hong Kong for using devices without a medical appearance to aid walking, such as umbrellas and hiking poles. There is a need to raise awareness of the risks of using umbrellas to aid walking and empower the user to make informed decisions when purchasing walking aid devices. In addition, there is a need to support the supply chain of walking aids, including umbrellas and hiking poles, to provide more information on device use, misuse, training, and maintenance.
PubMed: 38912102
DOI: 10.1177/15691861241254862 -
Cureus Jun 2024Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a multisystem paraneoplastic disorder due to an underlying plasma cell...
Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a multisystem paraneoplastic disorder due to an underlying plasma cell neoplasm, and its occurrence among HIV patients is extremely rare. The diagnosis of POEMS syndrome can be challenging in this context, particularly if its disabling polyneuropathy is misdiagnosed as neuropathy related to HIV. Herein, we report the case of a female patient with treated HIV who later developed POEMS syndrome. After a misdiagnosis of chronic inflammatory demyelinating polyneuropathy related to HIV and unsuccessful corticosteroids and cyclophosphamide therapies, the correct diagnosis of POEMS syndrome was made. The patient achieved significant hematological and neurological improvement after six cycles of lenalidomide. Autologous stem cell transplantation was then scheduled to prevent eventual relapses.
PubMed: 38912072
DOI: 10.7759/cureus.62820 -
Clinical Case Reports Jul 2024Noma is still around today and can be deadly if ignored. Prompt identification and comprehensive care are essential for averting permanent impairments and disfigurements.
KEY CLINICAL MESSAGE
Noma is still around today and can be deadly if ignored. Prompt identification and comprehensive care are essential for averting permanent impairments and disfigurements.
ABSTRACT
Noma is a rapid developing orofacial gangrene and a disabling disease that primarily affects young children who live in dangerous conditions. Underlying diseases such as HIV/AIDS and malnutrition can enhance the likelihood of Noma's emergence. This is a case of a 9-year-old girl patient who arrived malnourished and with an ulcerating communicating right mandibular soft tissue lesion as well as right hemiparesis which had an acute onset. The patient was likewise HIV positive discovered upon admission, possibly as a result of vertical transmission, and was an ART (antiretroviral therapy) treatment naive patient. A holistic treatment plan was installed and a positive clinical response was observed. Early treatment is key in Noma management.
PubMed: 38911917
DOI: 10.1002/ccr3.9111 -
Alzheimer's & Dementia (New York, N. Y.) 2024Alzheimer's disease and related dementias (ADRDs) and age-related hearing loss are the intersection of two major public health challenges. With age as the primary risk...
Alzheimer's disease and related dementias (ADRDs) and age-related hearing loss are the intersection of two major public health challenges. With age as the primary risk factor for both disease processes, the burden of ADRDs and age-related hearing loss is growing, and each field maintains significant barriers to broadscale identification and management that is affordable and accessible. With the disproportionate burden of ADRDs among racial and ethnic minority older adults and existing disparities within hearing care, both areas face challenges in achieving equitable access and outcomes across diverse populations. The publication of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) trial in July 2023 marked a significant moment in the fields of brain and hearing health. The ACHIEVE trial was the first randomized controlled trial to examine whether providing hearing intervention, specifically provision of hearing aids, compared to an education control, would reduce cognitive changes over 3 years. The participants most at risk for cognitive decline, with lower education, lower income, more likely to identify as Black, and have more cardiovascular risk factors, were the participants who benefited most from the hearing intervention and are also the least likely to be represented in research and the least likely to obtain hearing care. With growing evidence of the interconnection between cognitive and sensory health, we have an opportunity to prioritize equity, from purposeful inclusion of diverse participants in trials to influencing the emerging market of over-the-counter hearing aids to supporting expanded models of hearing care that reach those who have traditionally gone unserved. No longer can hearing go unrecognized by clinicians, researchers, and advocates for brain health. At the same time, the fields of brain and hearing health must center equity if we are going to meet the needs of diverse older adults in a world in which hearing health matters.
PubMed: 38911874
DOI: 10.1002/trc2.12484