EPIICAL

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.

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.

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.

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

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

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

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.

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.

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.