A5029362932- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- HIV/AIDS Research and Interventions
- Cytomegalovirus and herpesvirus research
- Immune Cell Function and Interaction
- HIV-related health complications and treatments
- SARS-CoV-2 and COVID-19 Research
- CRISPR and Genetic Engineering
- Fibromyalgia and Chronic Fatigue Syndrome Research
- T-cell and Retrovirus Studies
- Bacteriophages and microbial interactions
- Hepatitis C virus research
- Evolution and Genetic Dynamics
- SARS-CoV-2 detection and testing
- Immunotherapy and Immune Responses
- Respiratory viral infections research
- COVID-19 Clinical Research Studies
- Metabolism and Genetic Disorders
- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- Genomics and Phylogenetic Studies
- Virus-based gene therapy research
- Viral-associated cancers and disorders
- Antibiotics Pharmacokinetics and Efficacy
- Parvovirus B19 Infection Studies
Center for Cancer Research
2016-2025
Emory and Henry College
2025
Adelphi University
2025
National Cancer Institute
2015-2024
University of Michigan
2024
National Institutes of Health
2009-2023
Frederick National Laboratory for Cancer Research
2010-2021
Leidos Biomedical Research Inc. (United States)
2020
University at Buffalo, State University of New York
2020
University of Pittsburgh
2020
For HIV: Location, location, location HIV-infected cells linger even in the face of therapy, and this persistence, termed latent reservoir, is a major hurdle for curing HIV. HIV integrates itself into DNA its host cells. Could that affect reservoir? To find out, Maldarelli et al. drew blood from five patients on antiretroviral therapy analyzed sites where had inserted cells' (see Perspective by Margolis Bushman). In many cases, these were not random; often weaseled way genes help grow...
ABSTRACT To investigate the extent to which drug resistance mutations are missed by standard genotyping methods, we analyzed same plasma samples from 26 patients with suspected multidrug-resistant human immunodeficiency virus type 1 using a newly developed single-genome sequencing technique and compared it genotype analysis. Plasma were obtained prior exposure at least two antiretroviral classes who on failing regimen. Standard genotypes reverse transcriptase (RT)-PCR of bulk PCR product....
In HIV-1-infected individuals on currently recommended antiretroviral therapy (ART), viremia is reduced to <50 copies of HIV-1 RNA per milliliter, but low-level residual appears persist over the lifetimes most infected individuals. There controversy whether results from ongoing cycles viral replication. To address this question, we conducted 2 prospective studies assess effect ART intensification with an additional potent drug in 9 successful ART. By using assay single-copy sensitivity,...
Significance Reservoirs of HIV-infected cells persist during antiretroviral therapy, and understanding persistence is essential to develop HIV curative strategies. During replication, integrates into the host genome; most proviruses are not infectious, but some with replication-competent persist. Cells integrated can proliferate, potentially expanding reservoir, whether actually undergo expansion unknown. reactivation often lethal infected cells, others have reported finding no in expanded...
Background Most HIV-1-infected patients on effective antiretroviral therapy (ART) with plasma HIV-1 RNA levels below the detection limits of commercial assays have residual viremia measurable by more sensitive methods. We assessed whether adding raltegravir lowered level in such patients. Methods and Findings Patients receiving ART who had 50 copies/mL but detectable single copy assay (SCA) were randomized to add either or placebo their regimen for 12 weeks; then crossed-over other an...
HIV integrates its DNA into many sites in the host genome; thus integration can be used as markers to identify clonally expanded cells. We identified PBMCs and CD4+ T cells from patients these data show that there is extensive clonal expansion of infected have started determine sequences viral DNAs cells; are being study structure expression proviruses present >2500 individuals on combination anti-retroviral therapy (cART). About 40% integrations were In one patient, more than 50% a single...
Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation expression latently infected being explored as one the strategies deplete reservoir. In this study, we characterized ability romidepsin (RMD), histone deacetylase inhibitor approved for treatment T-cell lymphomas, activate HIV. an vitro model latency, RMD was most potent inducer (EC50 = 4.5 nM) compared with vorinostat (VOR; EC50 3,950...
The major obstacle to curing HIV infection is the persistence of cells with intact proviruses that can produce replication-competent virus. This reservoir believed exist primarily in CD4+ T-cells and stable despite years suppressive antiretroviral therapy. A potential mechanism for clonal expansion infected cells, but how often such clones carry has been controversial. Here, we used single-genome sequencing probe identical sequence matches among viruses recovered different viral outgrowth...
A single dose of the histone deacetylase inhibitor vorinostat (VOR) up-regulates HIV RNA expression within resting CD4(+) T cells treated, aviremic human immunodeficiency virus (HIV)-positive participants. The ability multiple exposures to VOR repeatedly disrupt latency has not been directly measured, our knowledge.Five participants in whom T-cell-associated (rc-RNA) increased after a agreed receive daily Monday through Wednesday for 8 weekly cycles. serum levels, peripheral blood...
A better understanding of changes in HIV-1 population genetics with combination antiretroviral therapy (cART) is critical for designing eradication strategies. We therefore analyzed genetic variation and divergence patients' plasma before cART, during suppression on after viral rebound. Single-genome sequences RNA were obtained from infected patients prior to cART (N = 14), 14) and/or rebound following interruption 5). Intra-patient diversity was measured by average pairwise difference...
Background It is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from pre-exposure prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 B; 31-year-old after infection with peak plasma RNA 220 copies/mL 3,343 copies/mL, respectively. Extensive testing blood tissue for persistence was performed, PrEP...
Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA) is detected in the bloodstream of some patients with disease 2019 (COVID-19), but it not clear whether this RNAemia reflects viremia (ie, virus particles) and how relates to host immune responses outcomes. Methods SARS-CoV-2 vRNA was quantified plasma samples from observational cohorts 51 COVID-19 including 9 outpatients, 19 hospitalized (non–intensive care unit [ICU]), 23 ICU patients. levels...
Combination antiretroviral therapy suppresses but does not eradicate human immunodeficiency virus type 1 (HIV-1) in infected persons, and low-level viremia can be detected despite years of suppressive therapy. Short-course (28-day) intensification standard combination is a useful approach to determine whether complete rounds HIV-1 replication rapidly cycling cells contribute persistent viremia. We investigated with the integrase inhibitor raltegravir decreases plasma RNA levels patients receiving
HIV type 1 (HIV-1) persists within resting CD4 + T cells despite antiretroviral therapy (ART). To better understand the kinetics by which cell infection (RCI) is established, we developed a mathematical model that accurately predicts ( r = 0.65, P 2.5 × 10 −4 ) initial frequency of RCI measured about year postinfection, based on time ART initiation and dynamic changes in viremia cells. In largest cohort patients treated during acute seronegative (AHI) whom has been stringently quantified,...
Neither the number of HIV-1 proviruses within individual infected cells in HIV-1–infected patients nor their genetic relatedness and between plasma virus are well defined. To address these issues we developed a technique to quantify genetically characterize DNA from single vivo. Analysis peripheral blood CD4 + T nine revealed that majority contain only one copy DNA, implying limited potential for recombination produced by cells. The similarity HIV populations implies ongoing exchange...
Studies on human immunodeficiency virus type 1 (HIV-1) diversity are critical for understanding viral pathogenesis and the emergence of immune escape variants design vaccine strategies. To investigate HIV-1 population genetics, we used single-genome sequencing to obtain pro-pol env sequences from longitudinal samples (n = 93) 14 acutely or recently infected patients. The first available sample after infection 12/14 patients revealed populations with low genetic diversity, consistent...
Significance Previously, we showed that the virus persists in human immunodeficiency (HIV)-infected individuals on antiretroviral therapy (ART) is derived from cells infected prior to initiating treatment. We also HIV-infected can undergo cellular proliferation during ART. However, it not known what fraction of persist ART are latent and actively producing HIV RNA. The method described here was developed determine produce RNA levels single cells, including have undergone proliferation....
ABSTRACT Understanding the origin of HIV variants during viral rebound may provide insight into composition reservoir and has implications for design curative interventions. single-genome sequences were obtained from 10 AIDS Clinical Trials Group participants who underwent analytic antiretroviral therapy (ART) interruption (ATI). Rebounding compared with those in pre-ART plasma all on-ART peripheral blood mononuclear cell (PBMC)-associated DNA RNA (CA-RNA) 7/10 participants. The highest...
ABSTRACT HIV infection is characterized by rapid and error-prone viral replication resulting in genetically diverse virus populations. The rate of accumulation diversity the mechanisms involved are under intense study to provide useful information understand immune evasion development drug resistance. To characterize after infection, we carried out an in-depth analysis single genome sequences pro-pol assess divergence estimate replicating population sizes a group treatment-naive HIV-infected...
Genetic recombination contributes to the diversity of human immunodeficiency virus (HIV-1). Productive HIV-1 is, however, dependent on both number genomes per infected cell and genetic relationship between these viral genomes. A detailed analysis proviruses their in cells isolated from peripheral blood tissue compartments is therefore important for understanding recombination, dynamics infection. To address issues, we used a previously developed single-cell sequencing technique quantify...
BACKGROUNDHIV-1 viremia that is not suppressed by combination antiretroviral therapy (ART) generally attributed to incomplete medication adherence and/or drug resistance. We evaluated individuals referred clinicians for nonsuppressible (plasma HIV-1 RNA above 40 copies/mL) despite reported ART and the absence of resistance current regimen.METHODSSamples were collected from at least 2 time points 8 donors who had more than 6 months. Single templates obtained plasma viral outgrowth cultured...
A quantitative real-time PCR (qRT-PCR) assay with single-copy sensitivity targeting HIV-1 gag RNA (the [gSCA]) has been used widely to quantify plasma viremia below the limit of detection clinical assays in patients on effective antiretroviral therapy (ART), but viral 15 30% samples amplifies inefficiently because primer/probe mismatches. We sought develop improved increased by improving nucleic acid recovery, designing qRT-PCR primers and a probe for highly conserved region integrase pol...