Joint evolution of CD4 and viral load trajectories over 2 years in an early-treated pediatric African cohort

Title

Joint evolution of CD4 and viral load trajectories over 2 years in an early-treated pediatric African cohort

Presenter

Sara Dominguez Rodriguez

Authors

S. Dominguez Rodriguez * (1), Ã. Ballesteros (1), L. Kuhn (2), T. Nhampossa (3), K. Otwombe (4), S. Shaun Barnabas (5), N. Klein (6), M.G. Lain (7), C. Giaquinto (8), P. Rossi (9), P. Rojo (1), A. Tagarro (1), EPIICAL Consortium

Institutions

(1) Fundación para la Investigación Biomédica del Hospital 12 de Octubre, Pediatric Infectious Diseases Unit, Madrid, Spain, (2) Gertrude H. Sergievsky Center, Vagelos College of Physititlcians and Surgeons, Columbia University Irving Medical Center, New York, United States, (3) Barcelona Institute for Global Health (ISGLOBAL), Barcelona, Spain, (4) Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa, (5) Family Centre For Research With Ubuntu (FAMCRU), Stellenbosch University, Cape Town, South Africa, (6) Africa Health Research Institute (AHRI), Durban, South Africa, (7) Fundação Ariel Glaser contra o SIDA Pediátrico, Maputo, Mozambique, (8) University of Padova, Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, Padova, Italy, (9) Ospedale Pediatrico Bambino Gesu, Division of Immune and Infectious Diseases, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy

BACKGROUND: In response to antiretroviral therapy (ART), some patients experience a discordant response, characterized either by a high CD4+ cell count despite persistent viremia or by viral suppression with low CD4+ cell count. Little is known about the meaning of discordant responses in children reported to be 10-20%. In this study, we analyze virologic and immunologic phenotypes, including a discordant response based on trajectories instead of arbitrary thresholds.
METHODS: This study was done within the EARTH Cohort, a prospective cohort enrolling perinatally HIV infected infants diagnosed in the first 3 months of life and treated after diagnosis, in Mozambique and South Africa. During 2-years of follow-up, the trajectories of CD4 and VL were calculated using KmL3D R package that implements k-means dedicated to clustering joint-trajectories. Optimum number of clusters was based on the Calinski-Harabatz criterium. Comparisons between clusters were assessed by the Kruskal-Wallis and Fisher test.
RESULTS: A total of 59 patients with at least 5 measurements of CD4 and VL were included in this study. Four robust clusters were selected. The participants in Cluster A (23/59 (39.0%)) presented virological failure and poor %CD4 reconstitution after treatment. They were treated later, and they had high VL and low %CD4 at ART initiation. Cluster B (19/59 (32.2%)) had participants who achieved viral suppression and had consistently high %CD4. A total of 17/59 (28.8%) patients presented discordant responses. Patients included in Cluster C (16/59 (27.1%)) presented a viral failure and high good CD4 reconstitution, and patients included in Cluster D (1/59 (1.7%)) also presented discordant response, in this case, viral suppression and poor CD4 reconstitution. Despite acceptable CD4 levels, patients with discordant responses presented higher rates of clinical progression (37.5%) (WHO stage III-IV) than those with viral suppression and good CD4 response (1/19 (5.3%)), p=0.015. Patients with discordant responses were more frequently treated with ART regimens including protease inhibitors (p=0.047).
CONCLUSIONS: A higher rate of discordant responses was present in this study (28.8%) compared to previous reports. The characterization of immunologic and virologic status of the patients could help in the design of personalized therapeutic interventions and in identifying patients for trials.

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