Clinical research to achieve antiretroviral therapy-free remission requires quantitative assays of the HIV-1 reservoir. Intact proviral DNA (IPD) measurement has greater throughput than the quantitative viral outgrowth assay (QVOA). In 25 individuals with well-documented long-term viral suppression, IPD levels and infectious units per million CD4+ T cells by QVOA strongly correlated (r = 0.59, P = .002), and IPD correlated with total cell-associated HIV-1 DNA and cell-associated HIV-1 RNA (r = 0.62 and r = 0.59, P ≤ .002). IPD may provide an accessible marker of inducible replication-competent virus, total numbers of infected cells, and cellular expression of HIV-1 RNA.
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http://dx.doi.org/10.1093/infdis/jiac030 | DOI Listing |
iScience
December 2024
Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC H2W 1R7, Canada.
Latent viral reservoirs (VRs) represent a main barrier to HIV cure. Thus, developing new approaches that can purge and eliminate VRs paves the path toward achieving an HIV-1 cure. APG-1387, a bivalent SMAC mimetic (SM), efficiently reactivates latent HIV expression in T cell line models and enhances active caspase 3 expression, a condition that typically leads to apoptosis.
View Article and Find Full Text PDFFront Immunol
November 2024
McMaster Immunology Research Centre, Department of Medicine, McMaster University, Hamilton, ON, Canada.
Depot-medroxyprogesterone acetate (DMPA) and Norethisterone Enanthate (NET-EN) are progestin-only injectable contraceptives widely used by women in sub-Sharan Africa, where incidence of HIV-1 and HSV-2 infection remains high. Studies indicate that DMPA usage can increase the risk of HSV-2 infection, but limited data indicate no increased risk with use of NET-EN. We therefore investigated the effects of NET-EN and DMPA on susceptibility to vaginal HSV-2 infection in ovariectomized (OVX) mice and effects on immune responses, particularly in the vaginal tract (VT).
View Article and Find Full Text PDFJ Infect Dis
October 2024
Department of Infectious Diseases, Hospital Universitari Germans Trias i Pujo0l, Badalona, Spain.
Objective: To compare the effects of first-line antiretroviral treatment (ART) with dolutegravir plus lamivudine (DTG+3TC) versus DTG plus emtricitabine/tenofovir alafenamide (FTC/TAF) on the evolution of the HIV-1 reservoir and immune activation biomarkers in people with HIV (PWH).
Methods: DUALITY was a 48-week, single-center, randomized, open-label clinical trial in ART-naïve PWH. Participants were randomized (1:1) to receive ART with DTG+3TC (2DR group) or DTG+FTC/TAF (3DR group).
EBioMedicine
November 2024
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address:
J Integr Neurosci
September 2024
Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Background: Infection of astrocytes by Human Immunodeficiency Virus (HIV-1) remains a topic of debate, with conflicting data, yet instances of astrocytes containing viral DNA have been observed . In this study, we aimed to elucidate potential routes through which astrocytes could be infected and their ability to produce infectious particles using primary human astrocytes.
Methods: We infected primary astrocytes derived from either neuroprogenitor cells (NPCs) or induced pluripotent stem cells (iPSCs) that express both C-X-C chemokine receptor type 4 (CXCR4) and the C-C chemokine receptor type 5 (CCR5) coreceptors, using either cell-free HIV-1 virus directly or cell-associated virus indirectly through infected macrophages and microglia.
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