Publications by authors named "Geoffrey Gottlieb"

Background: Institutions of higher education (IHE) have been a focus of SARS-CoV-2 transmission studies but there is limited information on how viral diversity and transmission at IHE changed as the pandemic progressed.

Methods: Here we analyze 3606 viral genomes from unique COVID-19 episodes collected at a public university in Seattle, Washington from September 2020 to September 2022.

Results: Across the study period, we found evidence of frequent viral transmission among university affiliates with 60% (n = 2153) of viral genomes from campus specimens genetically identical to at least one other campus specimen.

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Article Synopsis
  • The study assessed an unsupervised COVID-19 testing method where university participants self-swabbed at their convenience compared to traditional supervised testing.
  • Over the academic year from September 2021 to July 2022, unsupervised self-swabs were notably less frequent (26,800) than supervised ones (92,499), with higher error rates in unsupervised tests.
  • Results indicated that younger participants and certain racial/ethnic groups were more likely to choose unsupervised testing, with a drop in errors for unsupervised tests as time progressed—showing increasing feasibility over time.
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Vaccine effectiveness (VE) studies utilizing the test-negative design are typically conducted in clinical settings, rather than community populations, leading to bias in VE estimates against mild disease and limited information on VE in healthy young adults. In a community-based university population, we utilized data from a large SARS-CoV-2 testing program to estimate relative VE of COVID-19 mRNA vaccine primary series and monovalent booster dose versus primary series only against symptomatic SARS-CoV-2 infection from September 2021 to July 2022. We used the test-negative design and logistic regression implemented via generalized estimating equations adjusted for age, calendar time, prior SARS-CoV-2 infection, and testing frequency (proxy for test-seeking behavior) to estimate relative VE.

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The activity of lenacapavir against human immunodeficiency virus type 1 (HIV-1) has been extensively evaluated in vitro, but comparable data for human immunodeficiency virus type 2 (HIV-2) are scarce. We determined the anti-HIV-2 activity of lenacapavir using single-cycle infections of MAGIC-5A cells and multicycle infections of a T-cell line. Lenacapavir exhibited low-nanomolar activity against HIV-2, but was 11- to 14-fold less potent against HIV-2 in comparison to HIV-1.

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Background: Guidelines for SARS-CoV-2 have relied on limited data on duration of viral infectiousness and correlation with COVID-19 symptoms and diagnostic testing.

Methods: We enrolled ambulatory adults with acute SARS-CoV-2 infection and performed serial measurements of COVID-19 symptoms, nasal swab viral RNA, nucleocapsid (N) and spike (S) antigens, and replication-competent SARS-CoV-2 by viral growth in culture. We determined average time from symptom onset to a first negative test result and estimated risk of infectiousness, as defined by positive viral growth in culture.

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GSK2838232 (GSK232) is a novel maturation inhibitor that blocks the proteolytic cleavage of HIV-1 Gag at the junction of capsid and spacer peptide 1 (CA/SP1), rendering newly-formed virions non-infectious. To our knowledge, GSK232 has not been tested against HIV-2, and there are limited data regarding the susceptibility of HIV-2 to other HIV-1 maturation inhibitors. To assess the potential utility of GSK232 as an option for HIV-2 treatment, we determined the activity of the compound against a panel of HIV-1, HIV-2, and SIV isolates in culture.

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Background: Persistent infection with high-risk human papillomavirus (HPV) is associated with development of invasive cervical cancer.

Methods: Longitudinal data was collected from 174 Senegalese women. We employed marginal Cox proportional hazards models to examine the effect of human immunodeficiency virus (HIV) status (HIV positive vs HIV negative) and HIV type (HIV-1 vs HIV-2 vs dual HIV-1/HIV-2) on clearance of type-specific HPV infection.

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  • Set-point viral load (SPVL) is found to correlate with the age of HIV acquisition, suggesting that older individuals may face a selection for more virulent strains due to decreasing risks of infection as they age.
  • The study utilized a model (EvoNetHIV) tailored for men who have sex with men (MSM) to simulate how various behavioral and clinical factors influence the relationship between age and SPVL.
  • Results indicated that while SPVL increases with age when not accounting for source partner SPVL, this effect diminishes significantly when it is included, highlighting behavioral factors like relationship duration and coital frequency as important influencers on SPVL outcomes.
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Article Synopsis
  • Novel variants, especially Omicron, have emerged during the SARS-CoV-2 pandemic, prompting the need for effective genomic surveillance through university testing programs.* -
  • From September 2021 to February 2022, a study at a university identified 1,730 Omicron genomes out of nearly 3,000 positive cases, revealing Omicron's quicker transmission compared to Delta.* -
  • Even with high vaccination rates and strict health guidelines, Omicron outpaced Delta to become the dominant strain, resulting in a significant increase in COVID-19 cases within the university community.*
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Background: Integrase inhibitors (INIs) are a key component of antiretroviral therapy for human immunodeficiency virus-1 (HIV-1) and HIV-2 infection. Although INI resistance pathways are well-defined for HIV-1, mutations that emerge in HIV-2 in response to INIs are incompletely characterized.

Methods: We performed systematic searches of GenBank and HIV-2 drug resistance literature to identify treatment-associated mutations for phenotypic evaluation.

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Background: Second-line treatment of HIV-2 in resource-limited settings (RLS) is complicated by a lack of controlled trial data, limited availability of HIV-2-active antiretroviral drugs, and inadequate access to drug resistance testing. We conducted an implementation trial of a dried blood spot- (DBS) based, drug resistance genotype-informed antiretroviral therapy (ART) switching algorithm for HIV-2-infected patients in Senegal.

Methods: HIV-2-infected adults initiating or receiving ART through the Senegalese national AIDS program were invited to participate in this single-arm trial.

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Background: We aimed to evaluate a testing program to facilitate control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission at a large university and measure spread in the university community using viral genome sequencing.

Methods: Our prospective longitudinal study used remote contactless enrollment, daily mobile symptom and exposure tracking, and self-swab sample collection. Individuals were tested if the participant was exposed to a known SARS-CoV-2-infected person, developed new symptoms, or reported high-risk behavior (such as attending an indoor gathering without masking or social distancing), if a member of a group experiencing an outbreak, or at enrollment.

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Consultation with traditional healers (THs) is common among people living with HIV in sub-Saharan Africa. We conducted a prospective longitudinal study to determine the association between consultation with THs and HIV outcomes following 12 months of antiretroviral therapy (ART). HIV-infected individuals presenting for care and initiation of ART in Dakar and Ziguinchor, Senegal were eligible for enrollment.

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Pathogen populations can evolve in response to selective pressure from vaccine-induced immune responses. For HIV, models predict that viral adaptation, either via strain replacement or selection on de novo mutation, may rapidly reduce the effectiveness of an HIV vaccine. We hypothesized that behavioral risk compensation after vaccination may accelerate the transmission of vaccine resistant strains, increasing the rate of viral adaptation and leading to a more rapid decline in vaccine effectiveness.

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The goals of this study were to assess retention on antiretroviral therapy (ART) and to identify predictors of loss to follow-up (LTFU) among people living with HIV (PLHIV) in Senegal. HIV-positive individuals presenting for initiation of ART in Dakar and Ziguinchor were enrolled and followed for 12 months. Data were collected using interviews, clinical evaluations, laboratory analyses, chart review, and active patient tracing.

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Background: Understanding the impact of food insecurity on HIV outcomes is critical for the development and implementation of effective, evidence-based interventions to address food insecurity and improve the HIV care cascade. We conducted a prospective, longitudinal study to determine the impact of food insecurity on HIV outcomes in Senegal, West Africa.

Methods: HIV-infected individuals presenting for care and initiation of ART through the Senegalese National AIDS program in Dakar and Ziguinchor were eligible for enrollment.

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HIV set point viral load (SPVL), the viral load established shortly after initial infection, is a proxy for HIV virulence: higher SPVLs lead to higher risk of transmission and faster disease progression. Three models of test-and-treat scenarios, mainly in heterosexual populations, found that increasing treatment coverage selected for more virulent viruses. We modeled virulence evolution in a population of men who have sex with men (MSM) with increasing test-and-treat coverage.

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Background: Programmatic treatment outcome data for people living with human immunodeficiency virus type 2 (HIV-2) in West Africa, where the virus is most prevalent, are scarce.

Methods: Adults with HIV-2 initiating or receiving antiretroviral therapy (ART) through the Senegalese national AIDS program were invited to participate in this prospective, longitudinal observational cohort study. We analyzed HIV-2 viral loads, CD4 cell counts, antiretroviral drug resistance, loss to follow-up, and mortality.

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The treatment of HIV-2 in resource-limited settings (RLS) is complicated by the limited availability of HIV-2-active antiretroviral drugs and inadequate access to HIV-2 viral load and drug resistance testing. Dried blood spots (DBS)-based drug resistance testing, widely studied for HIV-1, has not been reported for HIV-2 and could present an opportunity to improve care for HIV-2-infected individuals. We selected 150 DBS specimens from ongoing studies of antiretroviral therapy (ART) for HIV-2 infection in Senegal and subjected them to genotypic drug resistance testing.

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The Senegal pre-exposure prophylaxis (PrEP) Demonstration Project was an open-label cohort study assessing the delivery of daily oral PrEP to HIV-negative female sex workers (FSWs) in four Ministry of Health (MoH)-run clinics in Dakar, Senegal. We assessed uptake, retention in care, and adherence over up to 12 months of follow-up as well as HIV infection rates. Between July and November 2015, 350 individuals were approached and 324 (92.

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We launched Infectious Disease electronic consultations (eConsults) in 2018. During the first 15.5 months, primary care practitioners submitted 328 eConsults; the most frequent reasons were a positive culture or polymerase chain reaction (PCR) result, syphilis, and latent tuberculosis.

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Background: Preexposure prophylaxis (PrEP) can reduce HIV acquisition among female sex workers (FSWs). However, changes in condomless sex frequency after PrEP initiation could reduce PrEP effectiveness when PrEP adherence is suboptimal as well as increase the risk of acquiring other sexually transmitted infections. Objective measures of condomless sex may be more accurate for determining changes in sexual behavior than self-reported measures.

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Background: HIV-1 and HIV-2 differ in their antiretroviral (ARV) susceptibilities and drug resistance mutations (DRMs).

Methods: We analyzed published HIV-2 pol sequences to identify HIV-2 treatment-selected mutations (TSMs). Mutation prevalences were determined by HIV-2 group and ARV status.

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