Feasibility and staff acceptability of implementing Xpert HIV-1 viral load point-of-care testing: a pilot study in San Francisco.

Background: Point-of-care HIV viral load testing may enhance patient care and improve HIV health services. We aimed to evaluate the feasibility and acceptability of implementing such testing in a high-volume community sexual health clinic in the United States.

Methods: We conducted a cross-sectional, mixed-methods study.

Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV disease.

Despite antiretroviral therapy (ART), HIV persists in latently-infected cells (the HIV reservoir) which decay slowly over time. Here, leveraging >500 longitudinal samples from 67 people living with HIV (PLWH) treated during acute infection, we developed a mathematical model to predict reservoir decay from peripheral CD4 + T cells. Nonlinear generalized additive models demonstrated rapid biphasic decay of intact DNA (week 0-5: t ~ 2.

Rapid Biphasic Decay of Intact and Defective HIV DNA Reservoir During Acute Treated HIV Disease.

Despite antiretroviral therapy (ART), HIV persists in latently-infected cells ("the reservoir") which decay slowly over time. Here, leveraging >500 longitudinal samples from 67 people with HIV (PWH) treated during acute infection, we developed a novel mathematical model to predict reservoir decay from peripheral CD4+ T cells. Nonlinear generalized additive models demonstrated rapid biphasic decay of intact DNA (week 0-5: t~2.

Host variation in type I interferon signaling genes (MX1), C-C chemokine receptor type 5 gene, and major histocompatibility complex class I alleles in treated HIV+ noncontrollers predict viral reservoir size.

Objective: Prior genomewide association studies have identified variation in major histocompatibility complex (MHC) class I alleles and C-C chemokine receptor type 5 gene (CCR5Δ32) as genetic predictors of viral control, especially in 'elite' controllers, individuals who remain virally suppressed in the absence of therapy.

Design: Cross-sectional genomewide association study.

Methods: We analyzed custom whole exome sequencing and direct human leukocyte antigen (HLA) typing from 202 antiretroviral therapy (ART)-suppressed HIV+ noncontrollers in relation to four measures of the peripheral CD4+ T-cell reservoir: HIV intact DNA, total (t)DNA, unspliced (us)RNA, and RNA/DNA.

HIV Disease Dynamics and Markers of Inflammation and CNS Injury During Primary HIV Infection and Their Relationship to Cognitive Performance.

Introduction: Early systemic and central nervous system viral replication and inflammation may affect brain integrity in people with HIV, leading to chronic cognitive symptoms not fully reversed by antiretroviral therapy (ART). This study examined associations between cognitive performance and markers of CNS injury associated with acute HIV infection and ART.

Methods: HIV-infected MSM and transgender women (average age: 27 years and education: 13 years) enrolled within 100 days from the estimated date of detectable infection (EDDI).

Microdrop Human Immunodeficiency Virus Sequencing for Incidence and Drug Resistance Surveillance.

Background: Precise and cost-efficient human immunodeficiency virus (HIV) incidence and drug resistance surveillances are in high demand for the advancement of the 90-90-90 "treatment for all" target.

Methods: We developed microdrop HIV sequencing for the HIV incidence and drug resistance assay (HIDA), a single-blood-draw surveillance tool for incidence and drug resistance mutation (DRM) detection. We amplified full-length HIV envelope and pol gene sequences within microdroplets, and this compartmental amplification with long-read high-throughput sequencing enabled us to recover multiple unique sequences.

TCF-1 regulates HIV-specific CD8+ T cell expansion capacity.

Although many HIV cure strategies seek to expand HIV-specific CD8+ T cells to control the virus, all are likely to fail if cellular exhaustion is not prevented. A loss in stem-like memory properties (i.e.

Group Testing for Severe Acute Respiratory Syndrome- Coronavirus 2 to Enable Rapid Scale-up of Testing and Real-Time Surveillance of Incidence.

High-throughput molecular testing for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) may be enabled by group testing in which pools of specimens are screened, and individual specimens tested only after a pool tests positive. Several laboratories have recently published examples of pooling strategies applied to SARS-CoV-2 specimens, but overall guidance on efficient pooling strategies is lacking. Therefore we developed a model of the efficiency and accuracy of specimen pooling algorithms based on available data on SAR-CoV-2 viral dynamics.

Seminal Plasma-Derived Extracellular-Vesicle Fractions from HIV-Infected Men Exhibit Unique MicroRNA Signatures and Induce a Proinflammatory Response in Cells Isolated from the Female Reproductive Tract.

The continuing spread of HIV/AIDS is predominantly fueled by sexual exposure to HIV-contaminated semen. Seminal plasma (SP), the liquid portion of semen, harbors a variety of factors that may favor HIV transmission by facilitating viral entry into host cells, eliciting the production of proinflammatory cytokines, and enhancing the translocation of HIV across the genital epithelium. One important and abundant class of factors in SP is extracellular vesicles (EVs), which, in general, are important intercellular signal transducers.

Seminal plasma promotes decidualization of endometrial stromal fibroblasts in vitro from women with and without inflammatory disorders in a manner dependent on interleukin-11 signaling.

Study Question: Do seminal plasma (SP) and its constituents affect the decidualization capacity and transcriptome of human primary endometrial stromal fibroblasts (eSFs)?

Summary Answer: SP promotes decidualization of eSFs from women with and without inflammatory disorders (polycystic ovary syndrome (PCOS), endometriosis) in a manner that is not mediated through semen amyloids and that is associated with a potent transcriptional response, including the induction of interleukin (IL)-11, a cytokine important for SP-induced decidualization.

What Is Known Already: Clinical studies have suggested that SP can promote implantation, and studies in vitro have demonstrated that SP can promote decidualization, a steroid hormone-driven program of eSF differentiation that is essential for embryo implantation and that is compromised in women with the inflammatory disorders PCOS and endometriosis.

Study Design, Size, Duration: This is a cross-sectional study involving samples treated with vehicle alone versus treatment with SP or SP constituents.

Clinical and Immunologic Outcomes After Immediate or Deferred Antiretroviral Therapy Initiation During Primary Human Immunodeficiency Virus Infection: The Sabes Randomized Clinical Study.

Background: In addition to demonstrated public health benefits on reducing transmission, it remains unclear how early antiretroviral therapy (ART) must be started after acquisition of human immunodeficiency virus (HIV) to maximize individual benefits.

Methods: We conducted an open-label randomized clinical study in Lima, Peru among adult men who have sex with men and transgender women with acute (HIV-antibody negative/HIV-1 RNA positive) or recent (confirmed negative HIV-antibody or RNA test within 3 months) HIV infection, who were randomized to start ART immediately versus defer by 24 weeks. We evaluated outcomes by treatment arm and immunologic markers by days since estimated date of detectible infection (EDDI).

Interpreting HIV diagnostic histories into infection time estimates: analytical framework and online tool.

Background: It is frequently of epidemiological and/or clinical interest to estimate the date of HIV infection or time-since-infection of individuals. Yet, for over 15 years, the only widely-referenced infection dating algorithm that utilises diagnostic testing data to estimate time-since-infection has been the 'Fiebig staging' system. This defines a number of stages of early HIV infection through various standard combinations of contemporaneous discordant diagnostic results using tests of different sensitivity.

Some Aspects of CD8+ T-Cell Exhaustion Are Associated With Altered T-Cell Mitochondrial Features and ROS Content in HIV Infection.

Background: Reversing or preventing T-cell exhaustion is an important treatment goal in the context of HIV disease; however, the mechanisms that regulate HIV-specific CD8 T-cell exhaustion are incompletely understood. Since mitochondrial mass (MM), mitochondrial membrane potential (MMP), and cellular reactive oxygen species (ROS) content are altered in exhausted CD8 T cells in other settings, we hypothesized that similar lesions may arise in HIV infection.

Methods: We sampled cryopreserved peripheral blood mononuclear cells from HIV-uninfected (n = 10) and HIV-infected participants with varying levels and mechanisms of viral control: viremic (VL > 2000 copies/mL; n = 8) or aviremic (VL < 40 copies/mL) due to antiretroviral therapy (n = 11) or natural control (n = 9).

Challenges to the performance of current HIV diagnostic assays and the need for centralized specimen archives: a review of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA) repository.

New challenges for diagnosis of HIV infection abound, including the impact on key viral and immunological markers of HIV vaccine studies, pre-exposure prophylaxis usage and breakthrough infections, and very early initiation of anti-retroviral treatment. These challenges impact the performance of current diagnostic assays, and require suitable specimens for development and evaluation. In this article we review and describe an archive developed by the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA), in order to identify the critical features required to create a centralized specimen archive to support these current and future developments.

Performance comparison of the Maxim and Sedia Limiting Antigen Avidity assays for HIV incidence surveillance.

Background: Two manufacturers, Maxim Biomedical and Sedia Biosciences Corporation, supply CDC-approved versions of the HIV-1 Limiting Antigen Avidity EIA (LAg) for detecting 'recent' HIV infection in cross-sectional incidence estimation. This study assesses and compares the performance of the two assays for incidence surveillance.

Methods: We ran both assays on a panel of 2,500 well-characterized HIV-1-infected specimens.

RAPID antiretroviral therapy: high virologic suppression rates with immediate antiretroviral therapy initiation in a vulnerable urban clinic population.

Objective: Little is known about long-term viral suppression rates for patients who start antiretroviral therapy (ART) soon after diagnosis. We describe virologic outcomes from the San Francisco-based Ward 86 Rapid ART Program for Individuals with an HIV Diagnosis (RAPID) ART program.

Design: Retrospective review of clinic-based cohort.

A generalizable method for estimating duration of HIV infections using clinical testing history and HIV test results.

Objective: To determine the precision of new and established methods for estimating duration of HIV infection.

Design: A retrospective analysis of HIV testing results from serial samples in commercially available panels, taking advantage of extensive testing previously conducted on 53 seroconverters.

Methods: We initially investigated four methods for estimating infection timing: method 1, 'Fiebig stages' based on test results from a single specimen; method 2, an updated '4th gen' method similar to Fiebig stages but using antigen/antibody tests in place of the p24 antigen test; method 3, modeling of 'viral ramp-up' dynamics using quantitative HIV-1 viral load data from antibody-negative specimens; and method 4, using detailed clinical testing history to define a plausible interval and best estimate of infection time.

Computational analysis of antibody dynamics identifies recent HIV-1 infection.

Accurate HIV-1 incidence estimation is critical to the success of HIV-1 prevention strategies. Current assays are limited by high false recent rates (FRRs) in certain populations and a short mean duration of recent infection (MDRI). Dynamic early HIV-1 antibody response kinetics were harnessed to identify biomarkers for improved incidence assays.

Infection Staging and Incidence Surveillance Applications of High Dynamic Range Diagnostic Immuno-Assay Platforms.

Background: Custom HIV staging assays, including the Sedia HIV-1 Limiting Antigen (LAg) Avidity EIA and avidity modifications of the Ortho VITROS anti-HIV-1+2 and Abbott ARCHITECT HIV Ag/Ab Combo assays, are used to identify "recent" infections in clinical settings and for cross-sectional HIV incidence estimation. However, the high dynamic range of chemiluminescent platforms allows differentiating recent and long-standing infection on signal intensity, and this raises the prospect of using unmodified diagnostic assays for infection timing and surveillance applications.

Methods: We tested a panel of 2500 well-characterized specimens with estimable duration of HIV infection with the 3 assays and the unmodified ARCHITECT.

Anti-HERV-K (HML-2) capsid antibody responses in HIV elite controllers.

Background: Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and while the majority are transcriptionally silent, the most recently integrated HERV, HERV-K (HML-2), remains active. During HIV infection, HERV-K (HML-2) specific mRNA transcripts and viral proteins can be detected. In this study, we aimed to understand the antibody response against HERV-K (HML-2) Gag in the context of HIV-1 infection.

Clinical and public health implications of acute and early HIV detection and treatment: a scoping review.

Introduction: The unchanged global HIV incidence may be related to ignoring acute HIV infection (AHI). This scoping review examines diagnostic, clinical, and public health implications of identifying and treating persons with AHI.

Methods: We searched PubMed, in addition to hand-review of key journals identifying research pertaining to AHI detection and treatment.

Semen amyloids participate in spermatozoa selection and clearance.

Unlike other human biological fluids, semen contains multiple types of amyloid fibrils in the absence of disease. These fibrils enhance HIV infection by promoting viral fusion to cellular targets, but their natural function remained unknown. The similarities shared between HIV fusion to host cell and sperm fusion to oocyte led us to examine whether these fibrils promote fertilization.