Combination Immune Checkpoint Blockade Enhances IL-2 and CD107a Production from HIV-Specific T Cells Ex Vivo in People Living with HIV on Antiretroviral Therapy.

In people with HIV (PWH) on antiretroviral therapy (ART), immune dysfunction persists, including elevated expression of immune checkpoint (IC) proteins on total and HIV-specific T cells. Reversing immune exhaustion is one strategy to enhance the elimination of HIV-infected cells that persist in PWH on ART. We aimed to evaluate whether blocking CTL-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), T cell Ig domain and mucin domain 3 (TIM-3), T cell Ig and ITIM domain (TIGIT) and lymphocyte activation gene-3 (LAG-3) alone or in combination would enhance HIV-specific CD4 and CD8 T cell function ex vivo.

Diverse effects of interferon alpha on the establishment and reversal of HIV latency.

HIV latency is the major barrier to a cure for people living with HIV (PLWH) on antiretroviral therapy (ART) because the virus persists in long-lived non-proliferating and proliferating latently infected CD4+ T cells. Latently infected CD4+ T cells do not express viral proteins and are therefore not visible to immune mediated clearance. Therefore, identifying interventions that can reverse latency and also enhance immune mediated clearance is of high interest.

HIV latency can be established in proliferating and nonproliferating resting CD4+ T cells in vitro: implications for latency reversal.

Objective: To determine whether latency can be established and reversed in both proliferating and nonproliferating CD4+ T cells in the same model in vitro.

Methods: Activated CD4+ T cells were infected with either a nonreplication competent, luciferase reporter virus or wild-type full-length enhanced green fluorescent protein (EGFP) reporter virus and cultured for 12 days. The cells were then sorted by flow cytometry to obtain two distinct T-cell populations that did not express the T-cell activation markers, CD69, CD25 and human leukocyte antigen (HLA)-DR: CD69CD25HLA-DR small cells (nonblasts) that had not proliferated in vitro following mitogen stimulation and CD69CD25HLA-DR large cells (which we here call transitional blasts) that had proliferated.

Efficacy of tenofovir disoproxil fumarate/emtricitabine compared with emtricitabine alone in antiretroviral-naive HIV-HBV coinfection in Thailand.

Background: Therapy for chronic hepatitis B with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC) or emtricitabine (FTC) is currently recommended for HIV-HBV coinfection. However, there is limited randomized data on the efficacy of combined therapy with TDF and FTC, especially in antiretroviral (ARV)-naive patients.

Methods: This was a prospective randomized clinical trial comparing the efficacy of HBV monotherapy with FTC versus TDF/FTC combination therapy in ARV-naive HIV-HBV coinfection.

Rapid loss of dendritic cell and monocyte responses to TLR ligands following venipuncture.

Blood samples from multiple sites are collected in multicenter trials, and frequently shipped to centralized laboratories for processing and comparable experimental evaluation. It is therefore of crucial interest to assess the preservation of immune cell functions after overnight shipment of whole blood. Here we evaluated the ability of pDCs, mDCs and monocytes to respond to TLR ligands at multiple timepoints following venipuncture as compared to immediate processing.