A5035584213- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- HIV/AIDS Research and Interventions
- Pneumocystis jirovecii pneumonia detection and treatment
- HIV-related health complications and treatments
- Biochemical and Molecular Research
- SARS-CoV-2 and COVID-19 Research
- Hepatitis C virus research
- Cytomegalovirus and herpesvirus research
- HIV, Drug Use, Sexual Risk
- Pregnancy and Medication Impact
- Advanced Biosensing Techniques and Applications
- SARS-CoV-2 detection and testing
- Microfinance and Financial Inclusion
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Maternal Mental Health During Pregnancy and Postpartum
- Atherosclerosis and Cardiovascular Diseases
- Antiplatelet Therapy and Cardiovascular Diseases
- Pneumonia and Respiratory Infections
- COVID-19 Clinical Research Studies
- RNA modifications and cancer
- vaccines and immunoinformatics approaches
- HIV/AIDS oral health manifestations
- Fatty Acid Research and Health
- Cholesterol and Lipid Metabolism
Case Western Reserve University
2017-2024
University School
2019-2024
University Hospitals of Cleveland
2022-2024
Jewish General Hospital
2006-2015
McGill University
2006-2015
AIDS United
2008-2015
Fonds de Recherche du Québec - Santé
2011
Bipar
2008
McGill University Health Centre
2004
Background. A population-based phylogenetic approach was used to characterize human immunodeficiency virus (HIV)—transmission dynamics in Quebec. Methods. HIV-1 pol sequences included primary HIV infections (PHIs; <6 months after seroconversion) from the Quebec PHI cohort (1998–2005; n = 215) and provincial genotyping program (2001–2005; 481). Phylogenetic analysis determined sequence interrelationships among unique PHIs (n 593) untreated 135) treated 660) chronically infected (CI) potential...
Objective: We have shown that HIV-1 clade C variants contain a valine codon 106 polymorphism (GTG) facilitates V106M transition (GTG←ATG) after selection with efavirenz (EFV). This study evaluates the prevalence of V106 and 106M (ATG) codons in clinical isolates as well effects on resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI). Methods: Genotypic analysis ascertained sequence diversity at 106, including both polymorphisms (GTA GTG) V106A (GCA) resistance-conferring...
ABSTRACT This study examines the persistence and fitness of multidrug-resistant (MDR) viruses acquired during primary human immunodeficiency virus infection (PHI). In four individuals, MDR infections persisted over entire period, ranging from 36 weeks to 5 years, in absence antiretroviral therapy. stark contrast, identified source partners two cases showed expected outgrowth wild-type (WT) within 12 treatment interruption. first PHI case, triple-class resulted low plasma viremia (1.6 3 log...
Background: Genotypic diversity among HIV-1 subtypes and circulating recombinant forms (CRF) may lead to distinct pathways drug resistance. This study evaluated subtype-related differences in the development of resistance culture tenofovir. Methods: Genotyping determined nucleotide subtypes. Representative subtype B, C, CRF1_AE, CRF2_AG, G, HIV-2 isolates were selected for tenofovir, lamivudine didanosine cell culture. Phenotypic assays effects K65R substitution reverse transcriptase (RT) on...
HIV post-treatment controllers (PTCs) are rare individuals who maintain low levels of viremia after stopping antiretroviral therapy (ART). Understanding the mechanisms control will inform development strategies aiming at achieving functional cure. In this study, we evaluated 22 PTCs from 8 AIDS Clinical Trials Group (ACTG) analytical treatment interruption (ATI) studies maintained viral loads ≤400 copies/mL for ≥24 wk. There were no significant differences in demographics or frequency...
Objectives: Population-based sequencing of primary/recent HIV infections (PHIs) can provide a framework for understanding transmission dynamics local epidemics. In Quebec, half PHIs represent clustered events. This study ascertained the cumulative implications clustering on onward drug resistance. Methods: HIV-1 pol sequence datasets were available all genotyped PHI (<6 months postseroconversion; n = 848 subtype B infections, 1997–2007). Phylogenetic analysis established events, based...
Phylodynamic analysis and epidemiologic data identified 3 patterns of spread primary human immunodeficiency virus type 1 infection (PHI) among men who have sex with (2001-2009): 420 unique PHIs, 102 small clusters (2-4 PHIs per cluster, n = 280), 46 large (5-31 450). Large disproportionately increased from 25.2% in 2005 to 39.1% 2009 (χ(2) 33.9, P < .001). Scalar expansion over 11 months (interquartile range, 3.5-25.5 months) correlated cluster membership size (r(2) 0.174, F 4.424, .047)....
Immune activation persists despite suppressive antiretroviral therapy (ART) in human immunodeficiency virus (HIV) infection and predicts non-Acquired Deficiency Syndrome (AIDS) comorbidities including cardiovascular disease. Activated platelets play a key role atherothrombosis inflammation, are hyperactivated chronic HIV infection. Aspirin is potent inhibitor of platelet through the cyclooxygenase-1 (COX-1) pathway. We hypothesized that contributes to immune aspirin would reduce improve...
Abstract Background Inflammation is associated with end-organ disease and mortality for people human immunodeficiency virus (PWH). Ruxolitinib, a Jak 1/2 inhibitor, reduces systemic inflammation individuals without (HIV) HIV reservoir markers ex vivo. The goal of this trial was to determine safety efficacy ruxolitinib PWH on antiretroviral therapy (ART). Methods AIDS Clinical Trials Group (ACTG) A5336 an open-label, multisite, randomized controlled (RCT). Participants were randomly assigned...
ABSTRACT We sequenced and phylogenetically analyzed the reverse transcriptase (RT) region of five human immunodeficiency virus type 1 isolates from treatment-naive Ethiopian émigrés to Israel. Heteroduplex mobility assays were performed confirm clade C status env genomic regions. The RT sequences showed that strains clustered with viruses, a KVEQ-specific motif silent mutations (amino acids 65, 106, 138, 161, respectively) at resistance sites was present in polymerase all studied subtype...
Objective: The authors previous studies documented persistence of multidrug resistance (MDR) acquired in five primary HIV-1infection (PHI) cases for 1–2 years the absence antiretroviral treatment. This study characterizes evolution transmitted wild-type (WT) (n = 15), resistant 10), and MDR 6) infections. Long-term infections (2–7 years), leading to one observed superinfection is documented. Methods: Genotypic changes circulating viral quasi-species were evaluated over 1.5–7 patients 31)...
We propose that a nucleotide template-based mechanism facilitates the acquisition of K65R mutation in subtype C human immunodeficiency virus type 1 (HIV-1). Different patterns DNA synthesis were observed using templates from viruses B or origin. When reverse transcriptase (RT) was employed to synthesize templates, preferential pausing seen at position responsible for AAG-to-AGG mutation. This did not occur when RT and template used. Template factors can therefore increase probability...
We used genotypic and phylogenetic analysis to determine integrase diversity among subtypes, studied natural polymorphisms mutations implicated in resistance inhibitors (INI) treatment-naïve persons (n = 220) -experienced individuals 24). Phylogenetics revealed 7 10% inter-subtype the reverse transcriptase (RT)/protease regions, respectively. Integrase sequencing identified a novel A/B recombinant which all viruses male-sex-male (MSM) transmission cluster 12) appeared possess subtype B A...
Abstract Background Despite effective antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection remains associated with higher morbidity and mortality, driven, in part, by increased inflammation. Our objective was to identify associations between levels of plasma biomarkers chronic inflammation, microbial translocation, monocyte activation, occurrence non-AIDS events. Methods Participants (141 cases, 310 matched controls) were selected from a longitudinal observational...
Objective: Among 1222 antiretroviral-naive patients who received dolutegravir (DTG) as part of first-line therapy, none has developed resistance against this compound after 48–96 weeks follow-up. Moreover, only four occurrences virological failure with mutations have been documented in previously drug-experienced DTG a first time integrase inhibitor component second-line regimen. The R263K mutation was observed two these individuals suboptimal background regimens. We selected at position...
Abstract Background People with human immunodeficiency virus (PWH) are at increased risk for comorbidities, and plasma interleukin 6 (IL-6) levels among the most robust predictors of these outcomes. Tocilizumab (TCZ) blocks receptor IL-6, inhibiting functions this cytokine. Methods This was a 40-week, placebo-controlled, crossover trial (NCT02049437) where PWH on stable antiretroviral therapy (ART) were randomized to receive 3 monthly doses TCZ or matching placebo intravenously. Following...
Latent cytomegalovirus (CMV) infection is immunomodulatory and could affect mRNA vaccine responsiveness. We sought to determine the association of CMV serostatus prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with antibody (Ab) titers after primary booster BNT162b2 vaccinations in healthcare workers (HCWs) nursing home (NH) residents. Nursing residents (N = 143) HCWs 107) were vaccinated serological responses monitored by serum neutralization activity against Wuhan...
Recently, we described a novel nucleotide template-based mechanism that may be the basis for facilitated acquisition of K65R resistance mutation in subtype C versus B human immunodeficiency virus type 1 (HIV-1). In this article, evaluated effects C-specific silent polymorphisms cell culture drug-selection experiments using nucleoside and reverse-transcriptase inhibitors. The pathway was selected more frequently contained at both positions 64 65 than wild-type NL4-3 virus. This is first...
ABSTRACT We have selected for resistance to etravirine (ETR) and efavirenz (EFV) in tissue culture using three subtype B, C, two CRF02_AG clinical isolates, grown cord blood mononuclear cells. Genotypic analysis was performed at baseline various weeks of selection. Phenotypic regard ETR, EFV, nevirapine (NVP) evaluated 25 30 all ETR-selected viruses viral clones that contained specific mutations were inserted by site-directed mutagenesis into pNL-4.3 AG plasmids. The results show ETR...
Human immunodeficiency virus type 2 (HIV-2) contains numerous natural polymorphisms in its protease (PR) gene that are implicated drug resistance the case of HIV-1. This study evaluated emergent PR HIV-2. Three HIV-2 isolates were selected for to amprenavir (APV), nelfinavir (NFV), indinavir (IDV), and tipranavir (TPV) cell culture. Genotypic analysis determined time appearance inhibitor (PI)-associated mutations compared Phenotypic susceptibility assays used determine levels resistance....
This study compared the incidence of HIV-1 variants harboring mutations conferring resistance to thymidine analogues, ie, analogue (TAMs), nonnucleoside reverse transcriptase (RT) inhibitors (NNMs), lamivudine (3TC) (ie, M184V), and protease (PIs) acquired in primary HIV infection (PHI) (n = 59) their observed prevalence a corresponding potential transmitter (PT) population persons resistant infections 380). Both these populations context this cohort analysis possessed similar demographics....
The current in-vitro study examined HIV-1 drug resistance patterns following etravirine (ETR) and rilpivirine (RPV) pressure in viruses containing baseline nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations.Several mutations were introduced into NL-4.3 (subtype B clone) by site-directed mutagenesis. This virus, together with two subtype C clinical isolates mutations, was passaged increasing of NNRTIs cord blood mononuclear cells. Genotypic analysis performed at different weeks....
ABSTRACT Antiretroviral-based microbicides may offer a means to reduce the sexual transmission of HIV-1. Suboptimal use microbicide may, however, lead development drug resistance in users that are already, or become, infected with In such cases, efficacy treatments be compromised since same (or similar) antiretrovirals used being developed as microbicides. To help predict which mutations develop context suboptimal use, HIV-1 primary isolates different subtypes and baseline profiles were...
M184V in HIV-1 reverse transcriptase is among the most common mutations patients failing antiretroviral therapy but found only rarely cases of transmitted drug resistance. To investigate this apparent paradox, we developed an allele-specific real-time PCR (AS-PCR) assay to determine transmission newly infected individuals. may occur a greater extent than previously thought. Persistence commonly involve linkage other resistance mutations. The presence as single substitution individuals was...
Numerous studies have suggested that the K65R reverse transcriptase (RT) mutation develops more readily in subtype C than B HIV-1. We recently showed this discrepancy lies partly template coding sequence predisposes RT to pause at site of mutagenesis. However, mechanism underlying observation and elevated rates development remained unknown. Here, we report DNA synthesis performed with templates consistently produced K65R-containing transcripts templates, regardless subtype-origin enzymes...