EPIICAL

27

Mar, 2020

Time to viral suppression in perinatally HIV-infected infants depends on the viral load and CD4 T-cell percentage at the start of treatment

 

Authors: Schröter J, Anelone A,  Yates A, de Boer RJ;  on behalf of the EPIICAL Consortium

Published in: J Acquir Immune Defic Syndr. 2020;83(5):522-529

 

Background Interventions aiming for an HIV cure would benefit from rapid elimination of virus after the onset of antiretroviral therapy (ART), by keeping the latent HIV reservoir small.

Setting We investigated HIV suppression in 312 perinatally infected infants starting ART within 6 months after birth from the EPPICC (European Pregnancy and Paediatric HIV Cohort Collaboration).

Methods To better understand kinetic differences in HIV suppression among infants, we investigated their individual viral load (VL) decay dynamics. We identified VL decay patterns and determined times to viral suppression (TTS). For infants with strictly declining VLs (n = 188), we used parameter fitting methods to estimate baseline VLs, decay rates, and TTS. We subsequently identified the parameters determining TTS by linear modeling.

Results The majority of infants suppress HIV VL after the onset of ART. Some children experienced a long TTS due to an “erratic” VL decay pattern. We cannot exclude that this is partly due to treatment complications and subsequent treatment changes, but these children were characterized by significantly lower CD4 percentages (CD4%) at start of treatment compared with those with a “clean” VL decline. Focusing on this “clean” subset, the TTS could be predicted by mathematical modeling, and we identified baseline VL and CD4% as the major factors determining the TTS.

Conclusions As VL steeply increases and CD4% constantly decreases in untreated HIV-infected infants, the progression of an HIV infection is largely determined by these 2 factors. To prevent a further disease progression, treatment should be initiated early after contracting HIV, which consequently shortens TTS.

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16

Mar, 2020

Mothers’ adherence helps in identifying more infants in need of extended prophylaxis

 

Authors: Dominguez-Rodriguez S, Rojo P, Lain MG,  Barnabas S, Lopez-Varela E, Otwombe K, Danaviah S, Nastouli E, Serna-Pasqual M, Gianuzzi V, Giaquointo C, Kuhn L, Tagarro A on behalf of the EPIICAL Consortium

Published in: 27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

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13

Mar, 2020

NK Cells are preserved by early ART in HIV-infected children with lower reservoir

 

Authors: Zicari S, Doria M, Domínguez-Rodríguez S, Cotugno N, Tagarro A, Rojo P, Nastouli E, Gartner K, Klein N, Foster C, Pahwa S, De Rossi A, Giaquinto C, Rossi P,  Palma P, for the EPIICAL consortium

Published in: 27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

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13

Mar, 2020

Poor outcome in early treated HIV perinatally infected infants in Africa

 

Authors: Tagarro A, Domínguez-Rodríguez S, Violari A, Cotton M, Mhampossa T, Klein N, Ramsagar N, Van Rensburg AJ, Behuhuma O, Vaz P,  Oletto A, Palma P, Rossi P, Rojo P, on behalf of the EPIICAL Consortium

Published in27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

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13

Mar, 2020

Assessment of HIV-1 DNA by single-genome sequencing in children on suppressive ART

 

Authors: Gärtner K, Gkouleli T, Byott M, Heaney J, Spyer MJ, DeRossi A, Persaud D, Palma P, Giaquinto C, Rojo P, Foster C, Marcelin AG, Rossi P, Nastouli E, for the EPIICAL consortium

Published in27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

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13

Mar, 2020

Cell-associated HIV-1 DNA/RNA in children: performance of real-time and digital PCR

 

Authors: Gärtner K, Gkouleli T, Heaney J, Grant P, Dominguez-Rodriguez S, Busby E, O’Sullivan D, Spyer MJ, Foster C, Rojo P, Persaud D, DeRossi A, Huggett J, Nastouli E, for the EPIICAL consortium

Published in27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

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13

Mar, 2020

Markers of HIV reservoir size in infected children on long-term viral control

 

Authors: Rinaldi S, Pallikkuth S, de Armas L, Pahwa R, Dominguez S, Cotugno N, Rojo Conejo P, Nastouli E, Gartner K, Klein N, Foster C, De Rossi A, Carlo Giaquinto C, Rossi P, Palma P, Pahwa S and EPIICAL Consortium

Published in:  27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

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13

Mar, 2020

Viral response in HIV infected infants starting ART at 1 month in Southern Mozambique

 

Authors: Lain MG, Vaz P, Ismael N,  Cantarutti A, Porcu G, Palma P, Cotugno N, Bila D, Rinaldi S,  Pallikkuth S, Pahwa R, Taibo E, Esmeralda Karajeanes E, Giaquinto C, Pahwa S.

Published in:  27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

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19

Feb, 2020

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

 

Authors: Cotugno N, Morrocchi E, Rinaldi S, et al; EPIICAL Consortium.

Published in: AIDS. 2020 Feb 3.

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 6 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.

19

Feb, 2020

Impact of early antiretroviral therapy initiation on HIV-specific CD4 and CD8 T cell function in perinatally infected children

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Authors: Rinaldi S, Pallikkuth S, Cameron M, et al.

Published in: J Immunol. 2020 Feb 1;204:540-549

Abstract Early initiation of antiretroviral therapy (ART) in vertically HIV-infected children limits the size of the virus reservoir, but whether the time of treatment initiation (TI) can durably impact host immune responses associated with HIV infection is still unknown. This study was conducted in PBMC of 20 HIV-infected virally suppressed children on ART (mean age 9.4 y), classified as early treated (ET; age at ART initiation ≤0.5 y, n = 14) or late treated (LT; age at ART initiation 1–10 y, n = 6). Frequencies and functions of Ag-specific CD4 (CD40L+) and CD8 (CD69+) T cells were evaluated by intracellular IL-2, IFN-γ, and TNF-α production with IL-21 in CD4 or CD107a, granzyme B and perforin in CD8 T cells following stimulation with HIV gp140 protein (ENV) or GAG peptides by multiparameter flow cytometry. ET showed a higher proportion of cytokine-producing ENV- and GAG-specific CD4 and CD8 T cells compared with LT. In particular, ET were enriched in polyfunctional T cells. RNA sequencing analysis showed upregulation of immune activation pathways in LT compared with ET. Our results suggest that timing of TI in HIV-infected children has a long-term and measurable impact on the quality of the HIV-specific T cell immune responses and transcriptional profiles of PBMC, reinforcing the importance of early TI.