Publications

12

Apr, 2020

Differences in inducibility of the latent HIV reservoir in perinatal and adult infection

 

Authors: Dhummakupt A, Reubens JH, Anderson T, et al.

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

Abstract The HIV latent reservoir in resting memory CD4+ T cells prevents cure. Novel therapies to reactivate and eliminate the reservoir are in clinical trials in adults, but not yet in pediatric populations.

HIV proviral reservoir size was determined in perinatal (N=11) and adult infections (N=10) by digital droplet PCR (ddPCR) and with the intact proviral DNA assay (IPDA) in perinatal samples. The inducibility of the latent reservoir was determined with the Tat/rev Induced Limiting Dilution Assay (TILDA) that uses single-round (12 hr) T cell stimulation of CD4+ T cells with PMA/ ionomycin to maximally activate cells to induce proviral expression, measured as multiply-spliced HIV RNA Units per 106 CD4 cells (msRUPM). Markers of immune activation (CD69, CD25 and HLA-DR) and exhaustion (PD-1, TIM-3 and TIGIT) were also assessed. An enhanced TILDA with addition of PHA and for 18 hours was performed to enhance proviral expression in perinatal infections. Non-parametric tests were used for differences between paired and unpaired measurements; correlations were quantified by Spearman rank coefficient.

The median age was 15.8 yrs with a median duration of suppression of 6.7 yrs for perinatal infections, and 40.5 yrs with a median duration of suppression of 7.3 yrs for adult infections.  We found that despite a higher proviral reservoir size (median 132.1 vs. 66.7 c/106 PBMCs) and similar rates of T cell activation with PMA/ionomycin (median %CD69 = 96.7% and 93.0%) in perinatal and adult infections, respectively, the size of the induced reservoir was significantly lower in perinatal than in adult infections (median msRUPM of 2.99 vs 11.92, p=0.020). With the enhanced TILDA, the size of the induced reservoir increased significantly in perinatal infections (1.5-fold to a median of 4.5 msRUPM; p=0.034), but not in adult infections. The proportion of induced provirus was significantly lower in perinatal infections at 1.6% compared with 4.0% in adult infections (p=0.030). At baseline, the proportion of HLA-DR+ T cells was significantly lower in perinatal compared with adult infections (median HLA-DR+ cells = 4.56% vs 10.5%, p=0.012), but not correlated with the induced reservoir size.

The inducibility of the latent reservoir is substantially lower in perinatal compared with adult infections, possibly due to differences in baseline states of immune activation, with implications for latency reversal strategies towards ART-free remission.

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6

Apr, 2020

How is immunosuppressive status affecting children and adults in SARS-CoV-2 infection? A systematic review

 

Authors: Minotti C, Tirelli F, Barbieri E, Giaquinto C, Donà D.

Published in: J Infect. 2020 Apr 23

Objectives SARS-CoV-2 infection has now a global resonance. Data on how COVID-19 is affecting immunocompromised patients are however few. With our study we aimed to systematically review the current knowledge on SARS-CoV-2 cases in children and adults with immunosuppression, to evaluate outcomes in this special population.

Methods A systematic review of literature was carried out to identify relevant articles, searching the EMBASE, Medline, and Google Scholar databases. Studies reporting data on pre-defined outcomes and related to immunosuppressed adults and children with SARS-CoV-2 were included.

Results Sixteen relevant articles were identified with 110 immunosuppressed patients, mostly presenting cancer, along with transplantation and immunodeficiency. Cancer was more often associated with a more severe course, but not necessarily with a bad prognosis. Our data show that both children and adults with immunosuppression seem to have a favorable disease course, as compared to the general population.

Conclusion Immunosuppressed patients with COVID-19 seem to be few in relation to the overall figures, and to present a favorable outcome as compared to other comorbidities. This might be explained by a hypothetical protective role of a weaker immune response, determining a milder disease presentation and thus underdiagnosis. Nevertheless, surveillance on this special population should be encouraged.

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6

Apr, 2020

Fecal-oral transmission of Sars-Cov-2 in children: is it time to change our approach?

 

Authors: Donà D, Minotti C, Costenaro P, Da Dalt L, Giaquinto C.

Published in: Pediatr Infect Dis J. 2020 Apr 16.

Abstract Starting from 2 pediatric cases of COVID-19, with confirmation at nasopharyngeal and rectal swabs, we considered the lesson learnt from previous Coronavirus epidemics and reviewed evidence on the current outbreak. Surveillance with rectal swabs might be extended to infants and children, for the implications for household contacts and isolation timing.

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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

Timing of HIV diagnosis in HIV-positive pregnant women giving birth in a high prevalence Russian region

 

Authors: Sconza R, Plotnikova Y, Plynsky A, Rozenberg V, Thorne C

Published in: 10th International Workshop on HIV & Women, 6th – 7 th March 2020, Boston, MA

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13

Mar, 2020

Global variations in pubertal growth in adolescents living with perinatal HIV

 

Authors: Crichton S, Jesson J, Aké-Assi MH, Belfrage E, Davies MA, Pinto J, Teasdale C, Van Lam N, Vreeman R, Wanless S, Williams P, Yotebieng M, Leroy V, Goodall R on behalf of the CIPHER Global Cohort Collaboration

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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