Plasma Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Biomarkers of Cognitive Decline in People Living with HIV.

Background: This study examined the relationship between neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) and cognition in people living with HIV (PLWH) at baseline and over time.

Methods: Plasma and clinical data were available from PLWH aged ≥45 years with HIV RNA <200 copies/mL enrolled in the AIDS Clinical Trials Group HAILO cohort study. We measured plasma NfL and GFAP using a single molecule array platform.

Safety and adherence to self-administered intravaginal 5-fluorouracil cream following cervical intraepithelial neoplasia (CIN) 2/3 treatment among HIV-positive women in Kenya: A phase 1 clinical trial.

Objective: To determine the safety, tolerance, and adherence to self-administered intravaginal 5% fluorouracil (5FU) cream as adjuvant therapy following cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) treatment among women living with HIV (WLWH) in Kenya.

Methods: A phase I pilot trial was performed among 12 WLWH in Kenya, aged 18-49 years between March 2023 and February 2024 (ClinicalTrial.gov NCT05362955).

Fannyhessea vaginae and clearance of Lactobacillus iners are associated with incident non-chlamydial non-Mycoplasma genitalium urethritis in men who have sex with women.

Background: The etiology of nongonococcal urethritis (NGU) is incompletely understood. We sought to determine if genitourinary bacterial diversity or specific taxa were associated with incident NGU.

Methods: From August 2014-July 2018, men who have sex with women attending a sexual health clinic were clinically evaluated, including Mycoplasma genitalium (MG) and Chlamydia trachomatis (CT) testing, at enrollment and six monthly visits.

Polyamines: Key Players in Immunometabolism and Immune Regulation.

Polyamines are small organic molecules ubiquitously present in all living organisms and function as crucial regulators of biological processes ranging from fundamental cellular metabolism to immune regulation. Dysregulation of polyamine metabolism has been implicated in numerous diseases, including neurodegenerative disorders, inflammatory conditions, autoimmune diseases, and cancer. This review provides an overview of pathophysiology of these conditions, highlighting polyamines' role in immunometabolic alterations in the context of immune regulation.

Nonhuman primate models of pediatric viral diseases.

Infectious diseases are the leading cause of death in infants and children under 5 years of age. exposure to viruses can lead to spontaneous abortion, preterm birth, congenital abnormalities or other developmental defects, often resulting in lifelong health sequalae. The underlying biological mechanisms are difficult to study in humans due to ethical concerns and limited sample access.

HIV-1 single transcription start site mutants display complementary replication functions that are restored by reversion.

HIV-1 transcription initiates at two positions, generating RNAs with either 1G or 3G 5' ends. The replication fates of these RNAs di\er, with viral particles encapsidating almost exclusively 1G RNAs and 3G RNAs retained in cells where they are enriched on polysomes and among spliced viral RNAs. Here, we studied replication properties of virus promoter mutants that produced only one RNA 5' isoform or the other: separately, in combination, and during spreading infection.

Pre-exposure prophylaxis implementation during incarceration: Perspectives of formerly incarcerated men and women.

The HIV prevalence is higher among individuals involved in the United States (U.S.) correctional system than those in general population.

Association of T-Cell Phenotypes With Peri-Coronary Inflammation in People With and Without HIV and Without Cardiovascular Disease.

Background: Persistent immune activation is linked to elevated cardiovascular diseases in people with HIV on antiretroviral therapy. The fat attenuation index (FAI) is a measure of peri-coronary inflammation that independently predicts cardiovascular disease risk in people without HIV. Whether FAI is associated with immune activation is unknown.

INCREASING THE ACCESSIBILITY AND RELEVANCE OF IMPLEMENTATION SCIENCE FOR FRONT-LINE IMPLEMENTERS.

Background: Implementation science has been heralded as a critical strategy for ending the HIV epidemic (EHE), and the United States (US) has made a tremendous financial investment in implementation research. However, several dynamics in its development and organization may alienate front-line implementers and recapitulate some of the same missteps that have stymied past translational work.

Setting: Increasing the accessibility and relevance of HIV implementation science for front-line implementers (e.

Exploring distinct modes of inter-spike cross-linking for enhanced neutralization by SARS-CoV-2 antibodies.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its Omicron subvariants drastically amplifies transmissibility, infectivity, and immune escape, mainly due to their resistance to most neutralizing antibodies. Thus, exploring the mechanisms underlying antibody evasion is crucial. Although the full-length native form of antibody, immunoglobulin G (IgG), offers valuable insights into the neutralization, structural investigations primarily focus on the fragment of antigen-binding (Fab).

A review of network models for HIV spread.

Background: HIV/AIDS has been a global health crisis for over four decades. Network models, which simulate human behavior and intervention impacts, have become an essential tool in guiding HIV prevention strategies and policies. However, no comprehensive survey of network models in HIV research has been conducted.

Conformational ensemble-based framework enables rapid development of Lassa virus vaccine candidates.

Lassa virus (LASV), an arenavirus endemic to West Africa, poses a significant public health threat due to its high pathogenicity and expanding geographic risk zone. LASV glycoprotein complex (GPC) is the only known target of neutralizing antibodies, but its inherent metastability and conformational flexibility have hindered the development of GPC-based vaccines. We employed a variant of AlphaFold2 (AF2), called subsampled AF2, to generate diverse structures of LASV GPC that capture an array of potential conformational states using MSA subsampling and dropout layers.

Single-cell analyses reveal that monocyte gene expression profiles influence HIV-1 reservoir size in acutely treated cohorts.

Elimination of latent HIV-1 is a major goal of AIDS research but the host factors determining the size of these reservoirs are poorly understood. Here, we investigated whether differences in host gene expression modulate the size of the HIV-1 reservoir during suppressive ART. Peripheral blood mononuclear cells (PBMC) from fourteen individuals initiating ART during acute infection who demonstrated effective viral suppression but varying magnitude of total HIV-1 DNA were characterized by single-cell RNA sequencing (scRNA-seq).

Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons.

Background: Twice-yearly subcutaneous lenacapavir has been shown to be efficacious for prevention of HIV infection in cisgender women. The efficacy of lenacapavir for preexposure prophylaxis (PrEP) in cisgender men, transgender women, transgender men, and gender-nonbinary persons is unclear.

Methods: In this phase 3, double-blind, randomized, active-controlled trial, we randomly assigned participants in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF).

Multilevel Resilience and Appointment Attendance Among African American/Black Adults with HIV: A Prospective Multisite Cohort Study.

Background: Attending clinic appointments supports HIV viral suppression, yet racial disparities are documented. We assessed whether multilevel resilience resources were associated with appointment attendance among African American/Black (AA/B) adults living with HIV in the United States.

Methods: We ascertained data from 291 AA/B clinical cohort participants from 2018 to 2021.

Development of lipopeptide-based HIV-1/2 fusion inhibitors targeting the gp41 pocket site with a new design strategy.

Emerging studies demonstrate that lipid conjugation is a vital strategy for designing peptide-based viral fusion inhibitors, and the so-called lipopeptides exhibit greatly improved antiviral activity. In the design of lipopeptides, a flexible linker between the peptide sequence and lipid molecule is generally required, mostly with a short polyethylene glycol or glycine-serine sequence. Very recently, we discovered that the helix-facilitating amino acid sequence "EAAAK" as a rigid linker is a more efficient method in the design of SARS-CoV-2 fusion inhibitory lipopeptides.

Cost-effectiveness of viral load testing for transitioning antiretroviral therapy-experienced children to dolutegravir in South Africa: a modelling analysis.

Background: For children with HIV on antiretroviral therapy (ART), transitioning to dolutegravir-containing regimens is recommended. The aim of this study was to assess whether introducing viral load testing to inform new nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) for children with HIV and viraemia alongside dolutegravir-based ART is beneficial and of good economic value.

Methods: We used the Cost-Effectiveness of Preventing AIDS Complications-Pediatric model to project clinical and cost implications of three strategies among a simulated cohort of South African children aged 8 years with HIV receiving abacavir-lamivudine-efavirenz: (1) continue current ART (no dolutegravir; abacavir-lamivudine-efavirenz); (2) transition all children with HIV to dolutegravir, keeping current NRTIs (dolutegravir; abacavir-lamivudine-dolutegravir); or (3) transition to dolutegravir based on viral load testing (viral load plus dolutegravir), keeping current NRTIs if virologically suppressed (abacavir-lamivudine-dolutegravir, 70% of cohort) or switching abacavir to zidovudine (zidovudine) if viraemic (zidovudine-lamivudine-dolutegravir, 30%).

Decoding protein dynamicity in DNA ligase activity through deep learning-based structural ensembles.

Numerous proteins perform their functions by transitioning between various structures. Understanding the conformational ensembles associated with these states is essential for uncovering crucial mechanistic aspects that regulate protein function. In this study, we utilized AlphaFold3 () to investigate the structural dynamics and mechanisms of enzymes involved in DNA homeostasis, using NAD-dependent Taq ligases and human DNA Ligase 1 as a case example.

Women's experiences and acceptability of self-administered, home delivered, intravaginal 5-Fluorouracil cream for cervical precancer treatment in Kenya.

Background: Innovative strategies are essential to meet the World Health Organization's 90/70/90 cervical cancer elimination targets, aiming for 90% access to precancer treatment globally by 2030. In low-and middle-income countries (LMICs) where most cervical cancer cases occur, access to precancer treatment is severely limited. Scalable solutions like self-administered topical therapies can help close this gap.

Focused learning by antibody language models using preferential masking of non-templated regions.

Existing antibody language models () are pre-trained using a masked language modeling () objective with uniform masking probabilities. While these models excel at predicting germline residues, they often struggle with mutated and non-templated residues, which are crucial for antigen-binding specificity and concentrate in the complementarity-determining regions (). Here, we demonstrate that preferential masking of the non-templated CDR3 is a compute-efficient strategy to enhance model performance.