Assessing advances in three decades of clinical antiretroviral therapy on the HIV-1 reservoir.

Background: Antiretroviral therapy (ART) has improved the clinical management of HIV-1 infection. However, little is known about how the latest ART recommendations affect the heterogeneity of HIV-1 reservoir size.

Methods: We used a complete statistical approach to outline parameters underlying diversity in HIV-1 reservoir size in a cohort of 892 people with HIV-1 (PWH) on suppressive ART for >3 years.

Impact of Dolutegravir plus Lamivudine as First-Line Antiretroviral Treatment on HIV-1 Reservoir and Inflammatory Markers in Peripheral Blood.

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).

Interplay of egg white gel pH and intragastric pH: Impact on breakdown kinetics and mass transport processes.

Egg white gels have been utilized as a model system to study protein breakdown kinetics based on physical and biochemical breakdown processes during in vitro gastric digestion. Additionally, the impact of regulating intragastric pH on the breakdown kinetic processes was investigated. The present study evaluated the impact of gel pH (based on the pH of protein dispersion prepared at pH 3, 5 and 7.

Caecum OX40+CD4 T-cell subset associates with mucosal damage and key markers of disease in treated HIV-infection.

Background: Blood OX40-expressing CD4 T-cells from antiretroviral (ART)-treated people living with HIV (PWH) were found to be enriched for clonally-expanded HIV sequences, hence contributing to the HIV reservoir. OX40-OX40L is also a checkpoint regulator of inflammation in multiple diseases. We explored gut mucosal OX40+CD4+ T-cells and their potential significance in HIV disease.

Altered T-cell subset distribution in the viral reservoir in HIV-1-infected individuals with extremely low proviral DNA (LoViReTs).

Background: HIV cure strategies aim to eliminate viral reservoirs that persist despite successful antiretroviral therapy (ART). We have previously described that 9% of HIV-infected individuals who receive ART harbor low levels of provirus (LoViReTs).

Methods: We selected 22 LoViReTs matched with 22 controls ART suppressed for more than 3 years with fewer than 100 and more than 100 HIV-DNA copies/10  CD4 T cells, respectively.

Robust HIV-specific CD4+ and CD8+ T-cell responses distinguish elite control in adolescents living with HIV from viremic nonprogressors.

Background: Elite controllers are therapy-naive individuals living with HIV capable of spontaneous control of plasma viraemia for at least a year. Although viremic nonprogressors are more common in vertical HIV-infection than in adults' infection, elite control has been rarely characterized in the pediatric population.

Design: We analyzed the T-cell immunophenotype and the HIV-specific response by flow cytometry in four pediatric elite controllers (PECs) compared with age-matched nonprogressors (PNPs), progressors and HIV-exposed uninfected (HEUs) adolescents.

VIP-SPOT: an Innovative Assay To Quantify the Productive HIV-1 Reservoir in the Monitoring of Cure Strategies.

Improved assays are critical to the successful implementation of novel HIV-1 cure strategies, given the limited ability of currently available assays to quantify true effects on the viral reservoir. As interventions based on immune clearance target infected cells producing viral antigens, irrespective of whether the viruses generated are infectious or not, we developed a novel assay to identify viral protein production at the single-cell level. The novel viral protein spot (VIP-SPOT) assay, based on the enzyme-linked ImmunoSpot (ELISpot) approach, quantifies the frequency of CD4 T cells that produce HIV antigen upon stimulation.

Early Initiation of Antiretroviral Therapy Following In Utero HIV Infection Is Associated With Low Viral Reservoirs but Other Factors Determine Viral Rebound.

Background: Early HIV diagnosis allows combination antiretroviral therapy (cART) initiation in the first days of life following in utero (IU) infection. The impact of early cART initiation on infant viral reservoir size in the setting of high-frequency cART nonadherence is unknown.

Methods: Peripheral blood total HIV DNA from 164 early treated (day 0-21 of life) IU HIV-infected South African infants was measured using droplet digital PCR at birth and following suppressive cART.

Crystal structure and mechanism of human carboxypeptidase O: Insights into its specific activity for acidic residues.

Human metallocarboxypeptidase O (hCPO) is a recently discovered digestive enzyme localized to the apical membrane of intestinal epithelial cells. Unlike pancreatic metallocarboxypeptidases, hCPO is glycosylated and produced as an active enzyme with distinctive substrate specificity toward C-terminal (C-t) acidic residues. Here we present the crystal structure of hCPO at 1.