Dataset Information

Early antiretroviral therapy-treated perinatally HIV-infected seronegative children demonstrate distinct long-term persistence of HIV-specific T-cell and B-cell memory.

ABSTRACT:

Objective

To investigate long-term persistence of HIV-specific lymphocyte immunity in perinatally HIV-infected children treated within the first year of life.

Design

Twenty perinatally HIV-infected children who received ART therapy within the first year of life (early treated) and with stable viral control (>5 years) were grouped according to their serological response to HIV.

Methods

Western blot analysis and ELISA defined 14 HIV-seropositive and six seronegative patients. Frequencies of gp140-specific T-cell and B-cell, and T-cell cytokine production were quantified by flow cytometry in both seronegatives and seropositives. Transcriptional signatures in purified gp140-specific B-cell subsets, in response to in-vitro stimulation with HIV peptides was evaluated by multiplex RT-PCR.

Results

Gp140-specific T cells and B cells persist at similar levels in both groups. A higher production of IL-21 in gp140-specific T cells was found in seropositives vs. seronegatives (P = 0.003). Gene expression in switched IgM-IgD- gp140-specific memory B cells after stimulation with HIV peptides in vitro demonstrated a differential expression of genes involved in signal transduction and activation after BCR/TLR triggering and B-cell activation. Genes relating to antibody production (PRDM1) and T-B cognate stimulation (CXCR4, IL21R) were differentially induced after in-vitro stimulation in seronegatives vs. seropositives suggesting a truncated process of B-cell maturation.

Conclusion

HIV-specific memory B and T cells persist in early treated regardless their serological status. Seronegatives and seropositives are distinguished by gp140-specific T-cell function and by distinct transcriptional signatures of gp140-specific B cells after in-vitro stimulation, presumably because of a different antigen exposure. Such qualitative insights may inform future immunotherapeutic interventions.

SUBMITTER: Cotugno N

PROVIDER: S-EPMC7531185 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:RationaleLung disease is a common cause of mortality and morbidity in HIV-infected adolescents, but there is limited information on the spectrum of lung function impairment in adolescents on antiretroviral therapy.ObjectivesTo investigate lung function in HIV-infected adolescents on antiretroviral therapy in the Cape Town Adolescent Antiretroviral Cohort (Cape Town, South Africa).MethodsA total of 515 South African adolescents, aged 9-14 years, stable on antiretroviral therapy for at least 6 months, underwent baseline lung function testing. Measures included spirometry, nitrogen multiple-breath washout, forced oscillation technique, 6-minute walk test, single-breath carbon monoxide diffusion testing, and bronchodilator response testing. A comparator group of 110 age- and ethnicity-matched HIV-uninfected adolescents was also tested.ResultsFor the HIV-infected adolescents (mean [SD] age 12 [1.6] years, 52% male), the median (interquartile range) duration of antiretroviral therapy was 7.6 (4.6-9.2) years. The median (interquartile range) nadir CD4 was 510.5 (274-903) cells/mm3. HIV-infected adolescents had significantly lower FEV1, FVC, FEV1/FVC, diffusing capacity of carbon monoxide, respiratory system compliance, and functional residual capacity than HIV-uninfected adolescents (P < 0.05 for all associations). HIV-infected adolescents had higher airway resistance and lung clearance index than HIV-uninfected adolescents (P < 0.05 for all associations). Although generally small in magnitude, these differences remained significant after adjusting for age, sex, and height. In addition, age, sex, height, and history of past lower respiratory tract infection or pulmonary tuberculosis were associated with reduced lung function.ConclusionsPerinatally infected South African HIV-infected adolescents on antiretroviral therapy have lower lung function than uninfected adolescents. Prior lower respiratory tract infection or pulmonary tuberculosis is associated with lower lung function.

Project description:BackgroundExisting studies have suggested decreased adherence and rebound in mortality in perinatally HIV-infected adolescents receiving antiretroviral therapy (ART) as compared to adults and young children.MethodsWe used both quantitative and qualitative approaches to identify factors influencing adherence among perinatally infected adolescents in Thailand. We analyzed data from 568 pairs of perinatally infected adolescents (aged 12-19) and their primary caregivers in the Teens Living With Antiretrovirals (TEEWA) study, a cross-sectional survey conducted in 2010-2012. We also conducted 12 in-depth interviews in 2014 with infected adolescents or their primary caregivers to elicit experiences of living with long-term ART.ResultsFrom the quantitative analysis, a total of 275 (48.4%) adolescents had evidence of suboptimal adherence based on this composite outcome: adolescents self-reported missing doses in the past 7 days, caregiver rating of overall adherence as suboptimal, or latest HIV-RNA viral load ≥1000 copies/ml. In multivariate logistic regression analysis, younger age, having grandparents or extended family members as the primary caregiver, caregiver-assessed poor intellectual ability, having a boy/girlfriend, frequent online chatting, self-reported unhappiness and easiness in asking doctors questions were significantly associated with suboptimal adherence. From the in-depth interviews, tensed relationships with caregivers, forgetfulness due to busy schedules, and fear of disclosing HIV status to others, especially boy/girlfriends, were important contributors to suboptimal adherence. Social and emotional support and counseling from peer group was consistently reported as a strong adherence-promoting factor.ConclusionOur findings highlight unique barriers of ART adherence among the perinatally infected adolescents. Future interventions should be targeted at helping adolescents to improve interpersonal relationships and build adaptive skills in recognizing and addressing challenging situations related to ART taking.

Project description:ObjectiveTo evaluate potential adverse associations of individual antiretroviral medications used in combination antiretroviral therapy regimens on cardiac structure and function in youth with perinatally-acquired HIV infection (PHIV).DesignPHIV youth (N = 325) enrolled in a prospective multisite cohort study had a single echocardiogram at age 7-16 years to evaluate cardiac function and structure.MethodsWe applied several statistical approaches to evaluate associations between use of 18 individual antiretroviral medications with Z-scores for 11 measures of left ventricular function and structure. These included simultaneously evaluating all antiretroviral medications in adjusted linear regression models controlling for the false discovery rate (FDR), applying hierarchical models to estimate individual antiretroviral medication effects as deviations from drug class means, and evaluating latent measures of cardiac function and structure underlying multiple echocardiographic parameters.ResultsYouth taking combination regimens with a protease inhibitor (69%) had significantly better cardiac function than those on other regimens. After FDR control and adjustment for other antiretroviral medications, no individual antiretroviral medication was significantly associated with any measure of left ventricular function, but zidovudine was associated with higher adjusted mean Z-scores for one measure of left ventricular structure (end-systolic wall stress). Factor analysis identified three latent factors: heart function, heart size, and heart wall stress. Lopinavir was associated with better heart function scores, whereas zidovudine was associated with higher wall stress scores. Zidovudine and nevirapine were associated with higher heart size factor scores.ConclusionsDespite cardioprotective effects of combination regimens in PHIV youth, individual antiretroviral medications were associated with altered cardiac structure, which could progress to symptomatic cardiomyopathy in adulthood.