Publications by authors named "Maria C Garcia-Guerrero"
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).
Article Synopsis
- - Viremic non-progressors (VNPs) are a rare group of HIV-1 individuals who maintain normal CD4 T cell counts despite high viral loads, resembling natural hosts of simian immunodeficiency virus, but the reasons for this are not fully understood.
- - A study using single-cell and multiomics methods examined 16 VNPs and 29 HIV+ progressors, revealing genetic factors like CCR5Δ32 heterozygosity and lower CCR5 expression, alongside reduced intestinal disruption and immune responses in VNPs.
- - The research highlights various traits contributing to the immune stability in VNPs, indicating important insights for potential HIV treatment strategies in the future.
Article Synopsis
- Researchers studied 284 young children in South Africa who started HIV treatment early to see how well they could control the virus after treatment.
- About 84% of these kids managed to hide the virus while on treatment, but only 32% were still virus-free after more than 3 years.
- Some boys were able to stay virus-free even after stopping their treatment for months, which might be linked to differences in how boys and girls' immune systems respond to the virus.
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.
View Article and Find Full Text PDFAn HLA-I signature favouring KIR-educated Natural Killer cells mediates immune control of HIV in children and contrasts with the HLA-B-restricted CD8+ T-cell-mediated immune control in adults.
PLoS Pathog
November 2021
Article Synopsis
- * In a study of over 300 children with HIV in South Africa, specific HLA alleles like Bw4 and low HLA-A expression were identified as strong indicators of better immune and viral control, unlike in adults where HLA-B plays a larger role.
- * The study also found that children with a high frequency of specific NK cell types showed better control over HIV, suggesting a potential link between immunogenetic signatures and improved outcomes in pediatric HIV cases.
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.
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.
View Article and Find Full Text PDFBackground: 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.
Article Synopsis
- Metallocarboxypeptidase Z (CPZ) is a unique enzyme in the M14 family due to its N-terminal Frizzled-like domain, which interacts with Wnt proteins.
- Researchers analyzed CPZ's enzymatic properties using specially designed dansylated peptide substrates and large peptide libraries, discovering that it requires C-terminal Arg or Lys for substrate binding.
- The study also showed that the presence of the Frizzled domain didn't affect CPZ's carboxypeptidase activity, and they created structural models to explore the interaction between the Fz and catalytic domains.
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.
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