Differential HIV-1 Proviral Defects in Children vs. Adults on Antiretroviral Therapy.

HIV-1 proviral landscapes were investigated using near-full-length HIV single-genome sequencing on blood samples from five children with vertically acquired infection and on ART for ~7-9 years. Proviral structures were compared to published datasets in children prior to ART, children on short-term ART, and adults on ART. We found a strong selection for large internal proviral deletions in children, especially deletions of the gene.

In vivo detection of antisense HIV-1 transcripts in untreated and ART-treated individuals.

Natural antisense transcripts (AST) are expressed in eukaryotes, prokaryotes, and viruses and can possess regulatory functions at the transcriptional and/or post-transcriptional levels. In vitro studies have shown that HIV-1 AST promote viral latency through epigenetic silencing of the proviral 5' long terminal repeat. However, expression of AST in vivo has not been convincingly demonstrated.

Differential HIV-1 Proviral Defects in Children vs. Adults on Antiretroviral Therapy.

HIV-1 proviral landscapes were investigated using near full-length HIV single-genome sequencing on blood samples from 5 children with vertically acquired infection and on ART for ~7-9 years. Proviral structures were compared to published datasets in children prior to ART, children on short-term ART, and adults on ART. We found a strong selection for large internal proviral deletions in children, especially deletions of the gene.

detection of HIV-1 antisense transcripts in untreated and ART-treated individuals.

Natural antisense transcripts are expressed in eukaryotes, prokaryotes, and viruses and can possess regulatory functions at the transcriptional and/or post-transcriptional levels. studies have shown that HIV-1 antisense transcripts (AST) promote viral latency through epigenetic silencing of the proviral 5' long terminal repeat (LTR). However, expression of HIV-1 AST have not been convincingly demonstrated.

Association between HIV-1 Nef-mediated MHC-I downregulation and the maintenance of the replication-competent latent viral reservoir in individuals with virally suppressed HIV-1 in Uganda: an exploratory cohort study.

Background: The persistence of a replication-competent latent viral reservoir (RC-LVR) during antiretroviral therapy (ART) is a barrier to the development of a cure for HIV-1, but the role of viral genes in influencing RC-LVR size is unclear. We aimed to assess whether the magnitude by which the HIV-1 accessory protein Nef evades the adaptive immune response by downregulating MHC-I or CD4, or both, from the surface of infected cells is associated with the rate at which the RC-LVR in people with HIV-1 changes during long-term ART (>1 year).

Methods: We conducted an exploratory cohort study in which nef genes were sequenced from outgrowth viruses derived from the quantitative viral outgrowth assay (QVOA) for a group of people with ART-suppressed HIV-1 in Uganda between 2015 and 2020.

Divergent populations of HIV-infected naive and memory CD4+ T cell clones in children on antiretroviral therapy.

BACKGROUNDNaive cells comprise 90% of the CD4+ T cell population in neonates and exhibit distinct age-specific capacities for proliferation and activation. We hypothesized that HIV-infected naive CD4+ T cell populations in children on long-term antiretroviral therapy (ART) would thus be distinct from infected memory cells.METHODSPeripheral blood naive and memory CD4+ T cells from 8 children with perinatal HIV on ART initiated at age 1.

HIV-1 control in vivo is related to the number but not the fraction of infected cells with viral unspliced RNA.

In the absence of antiretroviral therapy (ART), a subset of individuals, termed HIV controllers, have levels of plasma viremia that are orders of magnitude lower than non-controllers (NC) who are at higher risk for HIV disease progression. In addition to having fewer infected cells resulting in fewer cells with HIV RNA, it is possible that lower levels of plasma viremia in controllers are due to a lower fraction of the infected cells having HIV-1 unspliced RNA (HIV usRNA) compared with NC. To directly test this possibility, we used sensitive and quantitative single-cell sequencing methods to compare the fraction of infected cells that contain one or more copies of HIV usRNA in peripheral blood mononuclear cells (PBMC) obtained from controllers and NC.

Temporary increase in circulating replication-competent latent HIV-infected resting CD4+ T cells after switch to an integrase inhibitor based antiretroviral regimen.

Background: The principal barrier to an HIV cure is the presence of the latent viral reservoir (LVR), which has been understudied in African populations. From 2018 to 2019, Uganda instituted a nationwide rollout of ART consisting of Dolutegravir (DTG) with two NRTI, which replaced the previous regimen of one NNRTI and the same two NRTI.

Methods: Changes in the inducible replication-competent LVR (RC-LVR) of ART-suppressed Ugandans with HIV (n = 88) from 2015 to 2020 were examined using the quantitative viral outgrowth assay.

HIV Expression in Infected T Cell Clones.

The principal barrier to an HIV-1 cure is the persistence of infected cells harboring replication-competent proviruses despite antiretroviral therapy (ART). HIV-1 transcriptional suppression, referred to as viral latency, is foremost among persistence determinants, as it allows infected cells to evade the cytopathic effects of virion production and killing by cytotoxic T lymphocytes (CTL) and other immune factors. HIV-1 persistence is also governed by cellular proliferation, an innate and essential capacity of CD4+ T cells that both sustains cell populations over time and enables a robust directed response to immunological threats.

Temporary increase in circulating replication-competent latent HIV-infected resting CD4+ T cells after switch to an integrase inhibitor based antiretroviral regimen.

The principal barrier to an HIV cure is the presence of a latent viral reservoir (LVR) made up primarily of latently infected resting CD4+ (rCD4) T-cells. Studies in the United States have shown that the LVR decays slowly (half-life=3.8 years), but this rate in African populations has been understudied.

A Pre-Vaccination Baseline of SARS-CoV-2 Genetic Surveillance and Diversity in the United States.

COVID-19 vaccines were first administered on 15 December 2020, marking an important transition point for the spread of SARS-CoV-2 in the United States (U.S.).

Brief Report: Rebound HIV Viremia With Meningoencephalitis After Antiretroviral Therapy Interruption After Allogeneic Bone Marrow Transplant.

Background: Allogeneic bone marrow transplant (alloBMT) in people living with HIV can lead to the undetectable levels of HIV reservoirs in blood, even using highly sensitive assays. However, with antiretroviral therapy (ART) interruption, rebound of HIV viremia occurs. The source of this rebound viremia is of interest in HIV cure strategies.

2020 SARS-CoV-2 diversification in the United States: Establishing a pre-vaccination baseline.

Unlabelled: In 2020, SARS-CoV-2 spread across the United States (U.S.) in three phases distinguished by peaks in the numbers of infections and shifting geographical distribution.

Short Communication: Persistence of HIV After Allogeneic Bone Marrow Transplant in a Dually Infected Individual.

Allogeneic bone marrow transplant (alloBMT) with continuous antiretroviral therapy alone has not been shown to completely eradicate HIV, possibly due to HIV persistence in rare residual host cells or infection of donor cells. Within a trial of alloBMT in individuals with hematological malignancies and HIV (ClinicalTrials.gov, NCT01836068), we measured HIV reservoirs longitudinally using a quantitative viral outgrowth assay.

Assessment of West Nile Virus Lineage 2 Dynamics in Greece and Future Implications.

The emergence of West Nile Virus lineage 2 (WNV-2) has contributed to multiple major human outbreaks in Greece since 2010. Studies to date investigating biological and environmental factors that contribute to West Nile Virus (WNV) transmission have resulted in complex statistical models. We sought to examine open publicly available data to ascertain if a predictive risk assessment could be employed for WNV-2 in Greece.

Haemopoietic cell transplantation in patients living with HIV.

Haemopoietic cell transplantation is established as a standard treatment approach for people living with HIV who have haematological malignancies with poor prognosis. Studies with autologous and allogeneic haemopoietic cell transplantation suggest that HIV status does not adversely affect outcomes, provided that there is adequate infection prophylaxis. Attention to possible drug-drug interactions is important.

Allogeneic bone marrow transplantation with post-transplant cyclophosphamide for patients with HIV and haematological malignancies: a feasibility study.

Background: Allogeneic blood or marrow transplantation (alloBMT) is a potentially life-saving treatment for individuals with HIV and haematological malignancies; challenges include identifying donors and maintaining antiretroviral therapy (ART). The objectives of our study were to investigate interventions to expand donor options and to prevent ART interruptions for patients with HIV in need of alloBMT.

Methods: This single-arm, interventional trial took place at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (Baltimore, MD, USA).

Reduced HIV-1 latent reservoir outgrowth and distinct immune correlates among women in Rakai, Uganda.

HIV-1 infection remains incurable owing to the persistence of a viral reservoir that harbors integrated provirus within host cellular DNA. Increasing evidence links sex-based differences in HIV-1 immune responses and pathogenesis; however, little is known about differences in HIV-1 infection persistence. Here, we quantified persistent HIV-1 infection in 90 adults on suppressive antiretroviral therapy in Rakai, Uganda (57 female patients).

Impact of Myc in HIV-associated non-Hodgkin lymphomas treated with EPOCH and outcomes with vorinostat (AMC-075 trial).

EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) is a preferred regimen for HIV-non-Hodgkin lymphomas (HIV-NHLs), which are frequently Epstein-Barr virus (EBV) positive or human herpesvirus type-8 (HHV-8) positive. The histone deacetylase (HDAC) inhibitor vorinostat disrupts EBV/HHV-8 latency, enhances chemotherapy-induced cell death, and may clear HIV reservoirs. We performed a randomized phase 2 study in 90 patients (45 per study arm) with aggressive HIV-NHLs, using dose-adjusted EPOCH (plus rituximab if CD20+), alone or with 300 mg vorinostat, administered on days 1 to 5 of each cycle.

Recombination Analysis of Near Full-Length HIV-1 Sequences and the Identification of a Potential New Circulating Recombinant Form from Rakai, Uganda.

The Phylogenetics And Networks for Generalized HIV Epidemics in Africa (PANGEA-HIV) consortium has been vital in the generation and examination of near full-length HIV-1 sequences generated from Sub-Saharan Africa. In this study, we examined a subset ( = 275) of sequences from Rakai, Uganda, collected between August 2011 and January 2015. Sequences were initially screened with COMET for subtyping and then evaluated using bootscanning and phylogenetic inference.

Combined HIV-1 sequence and integration site analysis informs viral dynamics and allows reconstruction of replicating viral ancestors.

Understanding HIV-1 persistence despite antiretroviral therapy (ART) is of paramount importance. Both single-genome sequencing (SGS) and integration site analysis (ISA) provide useful information regarding the structure of persistent HIV DNA populations; however, until recently, there was no way to link integration sites to their cognate proviral sequences. Here, we used multiple-displacement amplification (MDA) of cellular DNA diluted to a proviral endpoint to obtain full-length proviral sequences and their corresponding sites of integration.

Phylogenetic inference for the study of within-host HIV-1 dynamics and persistence on antiretroviral therapy.

Although antiretroviral therapy (ART) is highly effective at inhibiting HIV-1 replication and preventing AIDS, it cannot eradicate the infection. Many studies have used viral genetic information from single-genome and deep sequencing of blood and tissue samples to investigate the mechanisms that sustain the HIV-1 reservoir. Sequence data are analysed by use of measurements of population diversity and divergence and by exploration of phylogenetic associations.

Comparison of Immune Responses to Different Versions of VLP Associated Stabilized RSV Pre-Fusion F Protein.

Efforts to develop a vaccine for respiratory syncytial virus (RSV) have primarily focused on the RSV fusion protein. The pre-fusion conformation of this protein induces the most potent neutralizing antibodies and is the focus of recent efforts in vaccine development. Following the first identification of mutations in the RSV F protein (DS-Cav1 mutant protein) that stabilized the pre-fusion conformation, other mutant stabilized pre-fusion F proteins have been described.

A quantitative approach for measuring the reservoir of latent HIV-1 proviruses.

A stable latent reservoir for HIV-1 in resting CD4 T cells is the principal barrier to a cure. Curative strategies that target the reservoir are being tested and require accurate, scalable reservoir assays. The reservoir was defined with quantitative viral outgrowth assays for cells that release infectious virus after one round of T cell activation.