HIV

27

May, 2022

Health Equity in Pediatric Drug Development: Translating Aspiration into Operation.

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Authors: Folayan MO, Conway M, Russo C, Diniz N, Jafta LP, Sam-Agudu NA, Bernays S, Santana VM, Epps C, Turner MA.

Published in: Springer Nature

31

Mar, 2022

Determinants of B-Cell Compartment Hyperactivation in European Adolescents Living With Perinatally Acquired HIV-1 After Over 10 Years of Suppressive Therapy

 

Authors: Ruggiero A, Pascucci G.R, Cotugno N, Domínguez-Rodríguez S, Rinaldi S, Tagarro A, Rojo P, Foster C, Bamford A, De Rossi A, Nastouli E, Klein N, Morrocchi E, Fatou B, Smolen K.K, Ozonoff A, Di Pastena M, Luzuriaga K, Steen H, Giaquinto C, Goulder P, Rossi P, Levy O, Pahwa S, Palma P, the EPIICAL Consortium

Published in: Frontiers in Immunology 

18

Mar, 2022

The subphenotypes of early-treated children living with HIV-1

 

Authors: S Domínguez-Rodríguez, A Tagarro, C Foster, P Palma, N Cotugno, AD Rossi, A Dalzini, SG. Pahwa, E Nastouli, K Gärtner, AG Marcelin, P Rossi, C Giaquinto, P Rojo

Presented at: CROI 2022

 

Abstract

Subphenotypes have been identified in several heterogeneous diseases. Having a specific subphenotype often has therapeutic implications or impacts disease progression. In this study, we aimed to assess if children with HIV may show subphenotypes according to clinical, virological and immunological features.

We collected data from 40 HIV+ children included in a cross-sectional multicentric study (CARMA Study, EPIICAL Consortium). All children commenced ART <2 years, suppressed (viral load (VL) <50 copies/ml) within 12 months and remained suppressed for >5 years. Immunological and virological assays were performed at a median of 12 years after ART initiation. We collected clinical and sociodemographic data, baseline VL, CD4 and CD8 data, age at ART, HIV DNA reservoir size, cell-associated RNA (CA-RNA), ultrasensitive VL, CD4 subsets (T effector CD25+, activated memory cells, Treg cells ), humoral-specific HIV response (T-bet B cells), innate response (CD56dim NK cells, NKp46+, perforin), exhaustion markers (PD-1, PD-L1, DNAM), CD8 senesence, and biomarkers for T-lymphocyte thymic output (TREC) and endothelial activation (VCAM). To build the subphenotypes, the most informative variables were selected using an unsupervised penalty selection. Hierarchical clustering was performed using Pearson correlation as distance metric and Ward.D2 as clustering method. Internal validation was applied to select the best number of clusters.

Three subphenotypes were revealed (Cluster 1 n=18, 45%; Cluster 2 n=11, 27.5%; Cluster 3 n=11, 27.5%). Cluster 1 (best controllers) consisted of early ART-treated patients with high baseline %CD4, low reservoir size, low WB score, high TREC values, and low VCAM values. In contrast, Cluster 3 (worst controller) consisted of later ART-treated patients with low baseline %CD4, high reservoir size, low TREC values, high innate response, immunosenescence markers and VCAM. Cluster 2 (low-level viremia, altered immune response) consisted of early-treated patients with low-level (10 to 50 c/mL) VL, high reservoir size but low CA-RNA, higher Treg CD4 than in the other clusters, low TREC, weak innate response and lower levels of T-bet expression.

Three subphenotypes with decreasing levels of viral control and increasing levels of immune well-being were discovered. Response to different therapies may be different across the different clusters.

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18

Mar, 2022

2-year outcome of early treated infants in Sub-Saharan Africa

 

Authors: A Tagarro, S Domínguez-Rodríguez, L Kuhn, T Nhampossa, K Otwombe, AJv Rensburg, N Klein, MG Lain, AI. Maiga, C Brehin, C Giaquinto, P Rossi, P Rojo

Presented at: CROI 2022

 

Abstract

The real-world evolution of very early treated children born with HIV in high-prevalence settings during first years of life is unclear. We assessed the probability of death, progression to AIDS, viral load (VL) suppression, immunosuppression, and continuation in care of a cohort of early treated children born with HIV.

EARTH-EPIICAL Cohort is underway at 2 rural and 4 urban sites in Mozambique, Mali, and South Africa (SA). Infants with HIV who started ART in the first 3 months of life, are followed at 2, 6 and 12 weeks, and then 6-monthly for 4 years. Hereby, we provide the probability of death, progression, suppression and continuation in care during the first 2 years of life with multivariable cox regression models were used. Backward stepwise elimination was applied to reach the final multivariable model.

212 participants were enrolled and followed during a median time of 17 [6.8;27.5] months; 84 reached 2 years of follow-up. ART started at 34 [26;74] days of life, mostly 3TC+ABC+LPV/r (65%). Adherence was suboptimal (<90%) in 56% of visits. 23 patients (10.8%) died, at a median of 2.5 [0.6;6.8] months of age. At 2 years, probability (P) of death was 12% (CI95%,7 to 17), (P) of progression was 11% (CI95%,6 to 16%), (P) of continuation in care, 80% (CI95%,74 to 86%), (P) of VL suppression was 46% (CI95%, 0.34-0.49), and (P) of severe IS, 54% (CI95%, 44 to 62). Death occurred predominantly in the first 6 months (74%); mostly due to pneumonia (43%), malnutrition (13%) or diarrhea (8.7%). (P) of death was associated with baseline VL 2.19 (1.4-3.3), and suboptimal adherence 2.88 (1.18-7.2). (P) of progression was associated with baseline VL 1.71 (CI95%,1.14-2.58), and weight for age 0.53 (CI95%,0.39-0.71). (P) of lost to follow up also was associated with baseline VL (HR, 1.60 (CI95%,1.06-2.40) and weight for age (HR, 1.67 (CI95%,1.11-2.50). (P) of suppression associated with baseline VL (HR, 0.60 (CI95%,0.51-0.71) and CD4% (HR, 1.04, (CI95%,1.01-1.06), p=0.01. (P) of severe IS was associated with baseline VL, (HR, 1.4 (CI95% 1.15-1.69), baseline CD4% (HR, 0.91 (0.88-0.93), baseline weight for age (HR, 0.86 (CI95%, 0.76-0.99), and Mozambique (HR 1.88 (CI95%, 1.16-3.1).

Despite early treatment and a close follow-up, death, progression, and severe IS remain high in children born with HIV in Africa, especially in the 6 first months. Additional strategies are required to improve the care of this population.

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18

Mar, 2022

Birth outcomes following prenatal exposure to dolutegravir: the DOLOMITE-EPPICC study

 

Authors: C Thorne, K Aebi-Popp, L Ene, M Floridia, AM Gamell, M Illan, H Peters, A Samarina, L Ragone, C Giaquinto, V Vannappagari

Presented at: CROI 2022

 

Abstract

Dolutegravir (DTG) is recommended and widely used during pregnancy for maternal viral suppression and preventing perinatal transmission of HIV. Our objective is to assess pregnancy and neonatal outcomes including birth defects following prenatal DTG use using real-world European data.

Dolomite-EPPICC is a multi-cohort European observational study of DTG use in pregnant women living with HIV and their infants. An analysis of prospectively collected data on all pregnancies with any prenatal DTG exposure and with birth outcomes was conducted among participating cohorts from Italy, Romania, the Russian Federation, Spain, Switzerland and UK/Ireland. Periconception exposure was defined as being within the first 6 weeks of gestation.

Overall, 550 pregnancies (540 singleton, 10 twin pregnancies) from 7 cohorts were included in the analysis resulting in 508 liveborn infants (491 singletons and 17 twins). Overall, 72.1% (365/506) pregnancies were in parous women. A total of 27 pregnancies ended in spontaneous abortion, 18 pregnancies were terminated and five ended in still birth. One termination was for neuronal migration disorder and severe microcephaly, with periconception DTG exposure. All stillbirths were exposed to periconception DTG, none with birth defects. Among the 508 liveborn infants, earliest DTG exposure was periconception for 326 (64.9%) infants, later in trimester 1 for 36 (7.2%) and in trimester 2/3 for 140 (27.9%); 6 had unknown timing of exposure. There were 21 infants with birth defects (4.1%, 95% CI 2.6, 6.2); one infant had 2 defects. The 22 defects were in the following systems: genitourinary (7), heart (4), limb (4 [polydactyly, 3]), gastrointestinal (2), chromosomal (1), other (4); no CNS defects were reported.

The prevalence rate for overall birth defects here is the same as recently reported from the Antiretroviral Pregnancy Registry for periconception exposure to DTG. Dolomite-EPPICC will continue to monitor use and safety of DTG-based regimens in pregnancy, noting that our sample size of periconception exposures is currently too small to exclude potential associations with rare birth defects like NTDs.

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21

Feb, 2022

Borrowing information across patient subgroups in clinical trials, with application to a paediatric trial

 

Authors: R.M. Turner, A Turkova, C.L. Moore, A Bamford, M Archary, L.N. Barlow-Mosha, M.F. Cotton, T.R. Cressey, E Kaudha, A Lugemwa, H Lyall, H.A. Mujuru, V Mulenga, V Musiime, P Rojo, G Tudor-Williams, S.B. Welch, D.M. Gibb, D Ford, I.R. White & and the ODYSSEY Trial Team

Published in: BMC Medical Research Methodology

21

Feb, 2022

Dolutegravir dosing for children with HIV weighing less than 20 kg: pharmacokinetic and safety substudies nested in the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

 

Authors: H Waalewijn, M.K Chan, P.D.J Bollen, H.A Mujuru, S Makumbi, A.R Kekitiinwa, E Kaudha, T Sarfati, G Musoro, A Nanduudu, A Lugemwa, P Amuge, C.L Moore, P Rojo, C Giaquinto, A Colbers, D.M Gibb, D Ford, A Turkova, D.M Burger

Published in: The Lancet

10

Feb, 2022

Treatment and monitoring of children and adolescents with hepatitis C in Russia: Results from a multi-centre survey on policy and practice

 

Authors: F Malik, V Chulanov, N Pimenov, A Fomicheva, R Lundin, N Levina, C Thorne, A Turkova, G Indofi

Published in: The Journal of viral elimination

30

Dec, 2021

Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children

 

Authors: A Turkova, E White, HA. Mujuru, AR. Kekitiinwa, CM. Kityo, A Violari, A Lugemwa, TR. Cressey, P Musoke, E Variava, MF. Cotton, M Archary, et al for the ODYSSEY Trial Team

Published in: New England Journal of Medicine

17

Dec, 2021

Size of HIV-1 reservoir is associated with telomere shortening and immunosenescence in early-treated European children with perinatally acquired HIV-1

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Authors: A Dalzini, G Ballin, S Dominguez-Rodriguez, P Rojo , M.R Petrara, C Foster, N Cotugno, A Ruggiero, E Nastouli, N Klein, S Rinaldi, S Pahwa, P Rossi, C Giaquinto, P Palma , A De Rossi1, and on behalf of EPIICAL Consortium

Published in: Journal of the International AIDS Society

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