Efficacy and Safety of Switching to Daily Bictegravir Plus Lenacapavir From a Complex Human Immunodeficiency Virus Treatment Regimen: A Randomized, Open-Label, Multicenter Phase 2 Study (ARTISTRY-1).

Background: Complex antiretroviral therapy (ART) regimens, such as those requiring multiple tablets, several doses per day, or both, can negatively affect quality of life and treatment adherence among people with human immunodeficiency virus (HIV).

Methods: ARTISTRY-1 is a phase 2/3, operationally seamless, randomized, open-label, multicenter, active-controlled study (GS-US-621-6289; NCT05502341). Phase 2 of the study enrolled adults with plasma HIV-1 RNA <50 copies/mL receiving a complex ART regimen for ≥6 months.

Consistent Effects of Early Remdesivir on Symptoms and Disease Progression Across At-Risk Outpatient Subgroups: Treatment Effect Heterogeneity in PINETREE Study.

Introduction: In the PINETREE study, early remdesivir treatment reduced risk of coronavirus disease 2019 (COVID-19)-related hospitalizations or all-cause death versus placebo by 87% by day 28 in high-risk, non-hospitalized patients. Here we report results of assessment of heterogeneity of treatment effect (HTE) of early outpatient remdesivir, focusing on time from symptom onset and number of baseline risk factors (RFs).

Methods: PINETREE was a double-blind, placebo-controlled trial of non-hospitalized patients with COVID-19 who were randomized within 7 days of symptom onset and had ≥ 1 RF for disease progression (age ≥ 60 years, obesity [body mass index ≥ 30], or certain coexisting medical conditions).

Extracellular Loops of the Treponema pallidum FadL Orthologs TP0856 and TP0858 Elicit IgG Antibodies and IgG-Specific B-Cells in the Rabbit Model of Experimental Syphilis.

The resurgence of syphilis in the new millennium has called attention to the importance of a vaccine for global containment strategies. Studies with immune rabbit serum (IRS) indicate that a syphilis vaccine should elicit antibodies (Abs) that promote opsonophagocytosis of treponemes by activated macrophages. The availability of three-dimensional models for Treponema pallidum's () repertoire of outer membrane proteins (OMPs) provides an architectural framework for identification of candidate vaccinogens with extracellular loops (ECLs) as the targets for protective Abs.

Structural Modeling of the Treponema pallidum Outer Membrane Protein Repertoire: a Road Map for Deconvolution of Syphilis Pathogenesis and Development of a Syphilis Vaccine.

Treponema pallidum, an obligate human pathogen, has an outer membrane (OM) whose physical properties, ultrastructure, and composition differ markedly from those of phylogenetically distant Gram-negative bacteria. We developed structural models for the outer membrane protein (OMP) repertoire (OMPeome) of T. pallidum Nichols using solved Gram-negative structures, computational tools, and small-angle X-ray scattering (SAXS) of selected recombinant periplasmic domains.

Babesia microti infection in a patient with multiple sclerosis treated with ocrelizumab.

Ocrelizumab is a humanized monoclonal anti-CD20 antibody approved for treatment of relapsing-remitting and primary progressive multiple sclerosis (MS). Rare parasitic infections have been reported in patients with lymphoproliferative disorders using rituximab, a chimeric anti-CD20 antibody used off-label for the treatment of MS. Here, we report a patient with MS on ocrelizumab with B-cell depletion who developed severe Babesia microti (B.

Evidence that immunization with TP0751, a bipartite Treponema pallidum lipoprotein with an intrinsically disordered region and lipocalin fold, fails to protect in the rabbit model of experimental syphilis.

Deconvolution of syphilis pathogenesis and selection of candidate syphilis vaccinogens requires detailed knowledge of the molecular architecture of the Treponema pallidum outer membrane (OM). The T. pallidum OM contains a low density of integral OM proteins, while the spirochete's many lipoprotein immunogens are periplasmic.

Simulating system dynamics of the HIV care continuum to achieve treatment as prevention.

The continuing HIV pandemic calls for broad, multi-sectoral responses that foster community control of local prevention and care services, with the goal of leveraging high quality treatment as a means of reducing HIV incidence. Service system improvements require stakeholder input from across the care continuum to identify gaps and to inform strategic plans that improve HIV service integration and delivery. System dynamics modeling offers a participatory research approach through which stakeholders learn about system complexity and about ways to achieve sustainable system-level improvements.

Early Fungicidal Activity as a Candidate Surrogate Endpoint for All-Cause Mortality in Cryptococcal Meningitis: A Systematic Review of the Evidence.

Background: Cryptococcal meningitis (CM) is a leading cause of HIV-associated mortality. In clinical trials evaluating treatments for CM, biomarkers of early fungicidal activity (EFA) in cerebrospinal fluid (CSF) have been proposed as candidate surrogate endpoints for all- cause mortality (ACM). However, there has been no systematic evaluation of the group-level or trial-level evidence for EFA as a candidate surrogate endpoint for ACM.

A retrospective and prospective analysis of trading sex for drugs or money in women substance abuse treatment patients.

Background: Trading sex for drugs or money is common in substance abuse treatment patients, and this study evaluated prevalence and correlates of this behavior in women with cocaine use disorders initiating outpatient care. In addition, we examined the relation of sex trading status to treatment response in relation to usual care versus contingency management (CM), as well as predictors of continued involvement in sex trading over a 9-month period.

Methods: Women (N=493) recruited from outpatient substance abuse treatment clinics were categorized according to histories of sex trading (n=215, 43.

Cancer prevention in HIV-infected populations.

People living with human immunodeficiency virus (HIV) are living longer since the advent of effective combined antiretroviral therapy (cART). While cART substantially decreases the risk of developing some cancers, HIV-infected individuals remain at high risk for Kaposi sarcoma, lymphoma, and several solid tumors. Currently HIV-infected patients represent an aging group, and malignancies have become a leading cause of morbidity and mortality.

Outcome Assessments in Clinical Trials of Cryptococcal Meningitis: Considerations on Use of Early Fungicidal Activity as a Potential Surrogate Endpoint for All-Cause Mortality.

Cryptococcal meningitis (CM) is a common disease in resource-challenged settings, with a high mortality within weeks of disease onset. Mortality remains high with current treatments, so more effective interventions are needed to decrease mortality. There has been interest in using the outcome assessment of quantification of fungus from cerebrospinal fluid as a replacement (surrogate) endpoint for all-cause mortality (ACM) as a means of decreasing sample size in randomized clinical trials in CM.

Bone marrow plasma cells are a primary source of serum HIV-1-specific antibodies in chronically infected individuals.

Several potent and broadly neutralizing Abs to HIV-1 have been isolated recently from peripheral blood B cells of infected individuals, based on prescreening of Ab activity in the serum. However, little is known regarding the cells that make the Abs that circulate in the blood. Accordingly, we investigated the most likely source, the bone marrow, of chronically HIV-1-infected individuals who were not receiving antiretroviral therapy.