A5012256749- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- HIV/AIDS drug development and treatment
- Cytomegalovirus and herpesvirus research
- HIV-related health complications and treatments
- Immune Cell Function and Interaction
- Viral gastroenteritis research and epidemiology
- T-cell and B-cell Immunology
- Viral-associated cancers and disorders
- Escherichia coli research studies
- COVID-19 epidemiological studies
- Atomic and Molecular Physics
- Particle accelerators and beam dynamics
- Bacteriophages and microbial interactions
- Electromagnetic Scattering and Analysis
- Chaos control and synchronization
- HIV/AIDS Impact and Responses
- Advanced Chemical Physics Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- stochastic dynamics and bifurcation
- Nonlinear Dynamics and Pattern Formation
- Herpesvirus Infections and Treatments
- Mathematical and Theoretical Epidemiology and Ecology Models
- Pelvic floor disorders treatments
- Animal Disease Management and Epidemiology
University of California, San Diego
2009-2021
VA San Diego Healthcare System
2003-2018
San Francisco VA Medical Center
2016
AIDS Clinical Trials Group
2014
Louisiana State University
2013
San Francisco General Hospital
2003
Bristol-Myers Squibb (United Kingdom)
2003
University Hospital of Zurich
2003
University of Edinburgh
2003
Duke University
1998
An infant born to a woman with human immunodeficiency virus type 1 (HIV-1) infection began receiving antiretroviral therapy (ART) 30 hours after birth owing high-risk exposure.ART was continued when detection of HIV-1 DNA and RNA on repeat testing met the standard diagnostic criteria for infection.After discontinued (when child 18 months age), levels plasma RNA, proviral in peripheral-blood mononuclear cells, antibodies, as assessed by means clinical assays, remained undetectable through...
HIV-1 reservoirs preclude virus eradication in patients receiving highly active antiretroviral therapy (HAART). The best characterized reservoir is a small, difficult-to-quantify pool of resting memory CD4(+) T cells carrying latent but replication-competent viral genomes. Because strategies targeting this are now being tested clinical trials, well-validated high-throughput assays that quantify urgently needed. Here we compare eleven different approaches for quantitating persistent 30 on...
Deoxyribonucleic acid (DNA) of the human immunodeficiency virus (HIV) provides most sensitive measurement residual infection in patients on effective combination antiretroviral therapy (cART). Droplet digital PCR (ddPCR) has recently been shown to provide highly accurate quantification DNA copy number, but its application HIV DNA, or other equally rare targets, not reported. This paper demonstrates and analyzes ddPCR measure frequency total (pol copies per million cells), episomal 2-LTR...
The computation of the electron-electron Coulomb interaction is one limiting factors in ab initio electronic structure calculations. computational requirements for calculating term with commonly used analytic integration techniques between Gaussian functions prohibit calculations large molecules and other nanosystems. Here, it shown that a generalization fast multipole method to charge distributions dramatically reduces quantum problem. Benchmark on graphitic sheets containing more than 400...
Quantifying latently infected cells is critical to evaluate the efficacy of therapeutic strategies aimed at reducing size long-lived viral reservoir, but low frequency these makes this very challenging.We developed TILDA (Tat/rev Induced Limiting Dilution Assay) measure with inducible multiply-spliced HIV RNA, as transcripts are usually absent in induced upon reactivation. requires less than a million cells, does not require RNA extraction and can be completed two days.In suppressed...
Patients in whom virologic suppression is achieved with highly active antiretroviral therapy (HAART) retain long-lived cellular reservoirs of human immunodeficiency virus type 1 (HIV-1); this retention an obstacle to sustained control infection. To assess the impact that initiating treatment during primary HIV-1 infection has on cell population, we analyzed decay kinetics DNA and infectivity associated cells activated ex vivo 27 patients who initiated before or <6 months after seroconversion...
Viral replication and latently infected cellular reservoirs persist in HIV-infected patients achieving undetectable plasma virus levels with potent antiretroviral therapy. We exploited a predictable drug resistance mutation the HIV reverse transcriptase to label track cells during defined intervals of treatment identify replenished by ongoing replication. Decay rates subsets paradoxically decreased time since establishment, reflecting heterogeneous lymphocyte activation clearance. Residual...
Background. The degree to which human immunodeficiency virus (HIV) continues replicate during antiretroviral therapy (ART) is controversial. We conducted a randomized, double-blind, placebo-controlled study assess whether raltegravir intensification reduces low-level viral replication, as defined by an increase in the level of 2–long terminal repeat (2-LTR) circles. Methods. Thirty-one subjects with ART-suppressed plasma HIV RNA <40 copies/mL and CD4+ T-cell count ≥350 cells/mm3 for ≥1 year...
The CD8+ T-cell is a key mediator of antiviral immunity, potentially contributing to control pathogenic lentiviral infection through both innate and adaptive mechanisms. We studied viral dynamics during antiretroviral treatment simian immunodeficiency virus (SIV) infected rhesus macaques following depletion test the importance cytotoxic effects in clearance cells productively with SIV. As previously described, plasma load (VL) increased was proportional magnitude GALT, confirming direct...
Early initiation of combination antiretroviral therapy (cART) to human immunodeficiency virus type 1 (HIV-1)-infected infants controls HIV-1 replication and reduces mortality.Plasma viremia (lower limit detection, <2 copies/mL), T-cell activation, HIV-1-specific immune responses, the persistence cells carrying replication-competent were quantified during long-term effective in 4 perinatally HIV-1-infected youth who received treatment early (the ET group) late LT group). Decay peripheral...
To provide insight into the dynamics and source of residual viremia in human immunodeficiency virus (HIV) patients successfully treated with antiretroviral therapy, 14 intensely monitored indinavir efavirenz sustaining HIV RNA at <50 copies/ml for >5 years were studied. Abacavir was added to regimen eight year 5. After first 9 months levels had reached a plateau ("residual viremia") that persisted over 5 years. Levels differed among ranged from 3.2 23 copies/ml. Baseline DNA only significant...
Human immunodeficiency virus (HIV) infection of the central nervous system (CNS) is a significant cause morbidity. The requirements for HIV adaptation to CNS neuropathogenesis and value CSF as surrogate activity in brain parenchyma are not well established. We studied 18 HIV-infected subjects, most with advanced some neurocognitive impairment but none evidence opportunistic or malignancy CNS. Clonal sequences C2-V3 env population pol from RNA cerebrospinal fluid (CSF) plasma were correlated...
Even when antiretroviral therapy (ART) is started early after infection, HIV DNA might persist in the central nervous system (CNS), possibly contributing to inflammation, brain damage and neurocognitive impairment. Paired blood cerebrospinal fluid (CSF) were collected from 16 HIV-infected individuals on suppressive ART: 9 participants ART <4 months of estimated date infection (EDI) ("early ART"), 7 >14 EDI ("late ART"). For each participant, functioning was measured by Global Deficit Score...
ABSTRACT Asymptomatic replication of human herpesviruses (HHV) is frequent in HIV-infected men and associated with increased T-cell activation HIV disease progression. We hypothesized that the presence cytomegalovirus (CMV) Epstein-Barr virus (EBV) (the most frequently detected HHV) might influence DNA decay during antiretroviral therapy (ART). investigated 607 peripheral blood mononuclear cell (PBMC) samples from 107 CMV-seropositive, who have sex men, started ART within a median 3 months...
HIV-1 often invades the CNS during primary infection, eventually resulting in neurological disorders up to 50% of untreated patients. The is a distinct viral reservoir, differing from peripheral tissues immunological surveillance, target cell characteristics and antiretroviral penetration. Neurotropic likely develops genotypic response this unique selective environment. We sought catalogue genetic features CNS-derived by analysing 456 clonal RNA sequences C2-V3 env subregion generated CSF...
To determine the influence of asymptomatic genital viral infections on cellular components semen and blood, we evaluated associations between numbers activation statuses CD4+ CD8+ T lymphocytes in both compartments seminal levels cytomegalovirus (CMV), herpes simplex virus (HSV), human immunodeficiency 1 (HIV). Paired blood samples were collected from 36 HIV-infected antiretroviral-naïve individuals 40 HIV-uninfected participants. We performed multiparameter flow cytometry analysis (CD45,...
Objective: The eradication of HIV necessitates elimination the latent reservoir. Identifying host determinants governing latency and reservoir size in setting antiretroviral therapy (ART) is an important step developing strategies to cure infection. We sought determine impact cell-intrinsic immunity on Design: investigated relevance a comprehensive panel established anti-HIV-1 restriction factors multiple virologic immunologic measures viral persistence HIV-1-infected, ART-suppressed...
BackgroundCharacterising the correlates of HIV persistence improves understanding disease pathogenesis and guides design curative strategies. This study investigated factors associated with integrated HIV-1 DNA load during consistently suppressive first-line antiretroviral therapy (ART).MethodTotal, integrated, 2-long terminal repeats (LTR) circular DNA, residual plasma RNA, T-cell activation markers, soluble CD14 (sCD14) were measured in peripheral blood 50 patients that had received 1–14...
Abstract Background Sex differences in human immunodeficiency virus (HIV) reservoir dynamics remain underexplored. Methods Longitudinal samples from virally suppressed midlife women (n = 59, median age 45 years) and age-matched men 31) were analyzed retrospectively. At each time point, we measured sex hormones (by means of enzyme-linked immunosorbent assay) cellular HIV DNA RNA digital droplet polymerase chain reaction). Number inducible RNA+ cells, which provides an upper estimate the...
The spatiotemporal dynamics of an excitable medium with multiple spiral defects is shown to vary smoothly system size from short-lived transients for small systems extensive chaos large systems. A comparison the Lyapunov dimension density average defect suggests per varying between 3 and 7. We discuss some implications these results experimental studies media.