AIDS-defining events and deaths in HIV-infected children and adolescents on antiretrovirals: a 14-year study in Thailand.

Mon, 25 Sep 2017 00:00:00 GMT-05:00 - Traisathit, Patrinee; Delory, Tristan; Ngo-Giang-Huong, Nicole; Somsamai, Rosalin; Techakunakorn, Pornchai; Theansavettrakul, Sookchai; Kanjanavanit, Suparat; Mekmullica, Jutarat; Ngampiyaskul, Chaiwat; Na-Rajsima, Sathaporn; Lallemant, Marc; Cressey, Tim R; Jourdain, Gonzague; Collins, Intira Jeannie; Le Coeur, Sophie
Εισαγωγή: Data are scarce on the long-term clinical outcomes of perinatally HIV-infected children and adolescents receiving antiretroviral therapy (ART) in low/middle-income countries. We assessed the incidence of mortality before (early) and after (late) 6-month of ART and of the composite outcome of new/recurrent AIDS-defining-event or death >6 months after ART start (late AIDS/death) and their associated factors.
Μέθοδοι: Study population was perinatally HIV-infected children (<=18 years) initiating ART within the Program for HIV Prevention and Treatment observational cohort (NCT00433030). Factors associated with late AIDS/death were assessed using competing risk regression models accounting for loss-to-follow-up, and included baseline and time-updated variables.
Αποτελέσματα: Among 619 children, "early" mortality incidence was 99 deaths per 1000-PYFU (95%CI; 69-142) and "late" mortality 6 per 1000-PYFU (95%CI; 4-9). Of the 553 children alive >6 months after ART initiation, median age at ART initiation was 6.4 years, CD4% 8.2% and HIV-RNA 5.1 log10 copies/mL. 38 (7%) children developed late AIDS/death after median time of 3.3 years: 24 died and 24 experienced new/recurrent AIDS-defining-events (10 subsequently died). Factors independently associated with late AIDS/death were: current age >=13 years (adjusted sub-distribution hazard-ratio 4.9; 95%CI; 2.4-10.1), HIV-RNA always >=400 copies/mL (12.3; 4.0-37.6), BMI-z-score always <-2 SD (13.7; 3.4-55.7), and hemoglobin <8g/dL at least once (4.6; 2.0-10.5).
Συμπεράσματα: After the initial 6 months of ART, being an adolescent, persistent viremia, poor nutritional status and severe anemia were associated with poor clinical outcomes. This supports the need for novel interventions that target children, particularly adolescents with poor growth and uncontrolled viremia. - (C) 2017

Adipose Tissue is Enriched for Activated and Late-differentiated CD8+ T cells, and Shows Distinct CD8+ Receptor Usage, Compared to Blood in HIV-infected Persons.

Mon, 25 Sep 2017 00:00:00 GMT-05:00 - Koethe, John R.; McDonnell, Wyatt; Kennedy, Arion; Abana, Chike O.; Pilkinton, Mark; Setliff, Ian; Georgiev, Ivelin; Barnett, Louise; Hager, Cindy C.; Smith, Rita; Kalams, Spyros A.; Hasty, Alyssa; Mallal, Simon
Εισαγωγή: Adverse viral and medication effects on adipose tissue contribute to the development of metabolic disease in HIV-infected persons, but T cells also have a central role modulating local inflammation and adipocyte function. We sought to characterize potentially pro-inflammatory T cell populations in adipose tissue among persons on long-term antiretroviral therapy, and assess whether adipose tissue CD8+ T cells represent an expanded, oligoclonal population.
Μέθοδοι: We recruited 10 HIV-infected, overweight and obese adults on efavirenz, tenofovir, and emtricitabine for >4 years with consistent viral suppression. We collected fasting blood and subcutaneous abdominal adipose tissue to measure the percentage of CD4+ and CD8+ T cells expressing activation, exhaustion, late-differentiation/senescence, and memory surface markers. We performed T cell receptor (TCR) sequencing on sorted CD8+ cells. We compared the proportion of each T cell subset, and the TCR repertoire diversity, in blood versus adipose tissue.
Αποτελέσματα: Adipose tissue had a higher percentage of CD3+CD8+ T cells compared to blood (61.0% vs. 51.7%, P<0.01), and was enriched for both activated CD8+HLA-DR+ T cells (5.5% vs. 0.9%, P<0.01) and late-differentiated CD8+CD57+ T cells (37.4% vs. 22.7%, P<0.01). Adipose tissue CD8+ T cells displayed distinct TCR[beta] V and J gene usage, and the Shannon's Entropy index, a measure of overall TCR[beta] repertoire diversity, was lower compared to blood (4.39 vs. 4.46; P=0.05).
Συμπεράσματα: Adipose tissue is enriched for activated and late-differentiated CD8+ T cells with distinct TCR usage. These cells may contribute to tissue inflammation and impaired adipocyte fitness in HIV-infected persons. - (C) 2017