A5081884086- HIV Research and Treatment
- COVID-19 epidemiological studies
- HIV/AIDS Research and Interventions
- HIV/AIDS drug development and treatment
- SARS-CoV-2 and COVID-19 Research
- Evolution and Genetic Dynamics
- Vaccine Coverage and Hesitancy
- Data-Driven Disease Surveillance
- COVID-19 Pandemic Impacts
- HIV, Drug Use, Sexual Risk
- Influenza Virus Research Studies
- Cytomegalovirus and herpesvirus research
- Virology and Viral Diseases
- Evolutionary Game Theory and Cooperation
- Respiratory viral infections research
- Herpesvirus Infections and Treatments
- Mental Health Research Topics
- Dermatological diseases and infestations
- Hepatitis C virus research
- Allergic Rhinitis and Sensitization
- Insects and Parasite Interactions
- Reproductive tract infections research
- Immunotherapy and Immune Responses
- Viral Infections and Outbreaks Research
- Mathematical and Theoretical Epidemiology and Ecology Models
Johns Hopkins University
2020-2025
Center for Disease Dynamics, Economics & Policy
2023
Harvard University
2013-2022
Evolutionary Genomics (United States)
2012-2021
Harvard University Press
2011-2019
Harvard–MIT Division of Health Sciences and Technology
2010-2014
Massachusetts Institute of Technology
2010-2014
Ragon Institute of MGH, MIT and Harvard
2014
Leibniz Institute of Virology (LIV)
2014
Blood Systems Research Institute
2014
Background: It is unknown whether the reduction in HIV-1 reservoirs seen after allogeneic hematopoietic stem cell transplantation (HSCT) with susceptible donor cells sufficient to achieve sustained remission. Objective: To characterize blood and tissues perform analytic antiretroviral treatment interruptions determine potential for HSCT lead sustained, antiretroviral-free Design: Case report characterization of immunity before interruption. Setting: Tertiary care center. Patients: Two men...
Reversal of HIV-1 latency by small molecules is a potential cure strategy. This approach will likely require effective drug combinations to achieve high levels reversal. Using resting CD4+ T cells (rCD4s) from infected individuals, we developed an experimental and theoretical framework identify latency-reversing agent (LRA) combinations. Utilizing ex vivo assays for intracellular mRNA virion production, compared 2-drug leading candidate LRAs identified multiple that effectively reverse...
Human populations are arranged in social networks that determine interactions and influence the spread of diseases, behaviours ideas. We evaluate long-term emotional states across a network. introduce novel form classical susceptible–infected–susceptible disease model which includes possibility for ‘spontaneous’ (or ‘automatic’) infection, addition to transmission (the SISa model). Using this framework data from Framingham Heart Study, we provide formal evidence positive negative behave like...
Massive research efforts are now underway to develop a cure for HIV infection, allowing patients discontinue lifelong combination antiretroviral therapy (ART). New latency-reversing agents (LRAs) may be able purge the persistent reservoir of latent virus in resting memory CD4+ T cells, but degree reduction needed remains unknown. Here we use stochastic model infection dynamics estimate efficacy LRA prevent viral rebound after ART interruption. We incorporate clinical data population-level...
Significance The HIV-1 latent reservoir cannot be eradicated by antiretroviral therapy (ART). is a major barrier to cure. To characterize the mechanisms that contribute persistence of reservoir, we examined clonally expanded cell populations carrying replication-competent and followed them longitudinally. Expanded clones harboring were identified in all study participants, but these emerge wane on time scale years. A similar pattern was viruses sampled from residual viremia. findings suggest...
Several combinations of 2 or 3 direct-acting antivirals (DAAs) can cure hepatitis C virus (HCV) in the majority treatment-naive patients. DAAs for HCV infection have similar mechanisms action and chemical structures to antiretrovirals human immunodeficiency (HIV) infection. Generic are currently manufactured at very low prices, treat 10 million people with HIV/AIDS developing countries.Four DAAs, either phase development recent approval (daclatasvir, sofosbuvir, simeprevir, faldaprevir),...
Abstract The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden daily adherence have not yet been developed. Here we describe an oral dosage form composed distinct drug–polymer matrices which achieved week-long systemic drug levels antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations viral dynamics patient patterns indicate such would reduce therapeutic failures...
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...
BackgroundThe London patient (participant 36 in the IciStem cohort) underwent allogeneic stem-cell transplantation with cells that did not express CCR5 (CCR5Δ32/Δ32); remission was reported at 18 months after analytical treatment interruption (ATI). Here, we present longer term data for this (up to 30 ATI), including sampling from diverse HIV-1 reservoir sites.MethodsWe used ultrasensitive viral load assays of plasma, semen, and cerebrospinal fluid (CSF) samples detect RNA. In gut biopsy...
In the absence of pharmaceutical interventions, social distancing is being used worldwide to curb spread COVID-19. The impact these measures has been inconsistent, with some regions rapidly nearing disease elimination and others seeing delayed peaks or nearly flat epidemic curves. Here we build a stochastic model examine effects COVID-19 clinical progression transmission network structure on outcomes interventions. Our simulations show that long delays between adoption control observed...
Many behavioral phenomena have been found to spread interpersonally through social networks, in a manner similar infectious diseases. An important difference between contagion and traditional diseases, however, is that can be acquired by non-social mechanisms as well transmission. We introduce novel theoretical framework for studying these (the SISa model) adapting classic disease model include the possibility 'automatic' (or 'spontaneous') infection. provide an example of use this examining...
Infections with rapidly evolving pathogens are often treated using combinations of drugs different mechanisms action. One the major goal combination therapy is to reduce risk drug resistance emerging during a patient's treatment. Although this strategy generally has significant benefits over monotherapy, it may also select for multidrug-resistant strains, particularly long-term treatment chronic infections. these strains present an important clinical and public health problem. Complicating...
SIV-infected rhesus macaques on antiretroviral therapy experienced a reduction in the SIV reservoir after treatment with TLR7 agonists.
One of the most important advancements in theoretical epidemiology has been development methods that account for realistic host population structure. The central finding is heterogeneity contact networks, such as presence 'superspreaders', accelerates infectious disease spread real epidemics. Disease control also complicated by continuous evolution pathogens response to changing environments and medical interventions. It remains unclear, however, how structure influences these adaptive...
Clonal expansion of infected CD4+ T cells is a major mechanism HIV-1 persistence and barrier to achieving cure. Potential causes are homeostatic proliferation, effects integration, interaction with antigens. Here, we show that it possible link antigen responsiveness, the full proviral sequence, integration site, cell receptor β-chain (TCRβ) sequence examine role recurrent antigenic exposure in maintaining reservoir. We isolated CMV- Gag-responding from 10 treated individuals. Proviral...
Monitoring the efficacy of novel reservoir-reducing treatments for HIV is challenging. The limited ability to sample and quantify latent infection means that supervised antiretroviral therapy (ART) interruption studies are generally required. Here we introduce a set mathematical statistical modeling tools aid in design interpretation ART-interruption trials. We show how likely size remaining reservoir can be updated real-time as patients continue off treatment, by combining output laboratory...
Abstract Massive unemployment during the COVID-19 pandemic could result in an eviction crisis US cities. Here we model effect of evictions on SARS-CoV-2 epidemics, simulating viral transmission within and among households a theoretical metropolitan area. We recreate range urban epidemic trajectories project course under two counterfactual scenarios, one which strict moratorium is place enforced, another are allowed to resume at baseline or increased rates. find, across that lead significant...
Our ability to forecast epidemics far into the future is constrained by many complexities of disease systems. Realistic longer-term projections may, however, be possible under well-defined scenarios that specify state critical epidemic drivers. Since December 2020, U.S. COVID-19 Scenario Modeling Hub (SMH) has convened multiple modeling teams make months ahead SARS-CoV-2 burden, totaling nearly 1.8 million national and state-level projections. Here, we find SMH performance varied widely as a...
Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. For the 2021-22 and 2022-23 seasons, 26 forecasting teams provided national jurisdiction-specific probabilistic predictions of weekly confirmed hospital admissions for one-to-four weeks ahead. Forecast skill is evaluated using Weighted Interval Score (WIS), relative WIS, coverage. Six out 23 models outperform baseline model across forecast locations in 12 18 2022-23. Averaging all...