The CARMA study: early infant antiretroviral therapy-timing impacts on total HIV-1 DNA quantitation 12 Years later

Foster, Caroline, Domínguez-Rodríguez, Sara, Tagarro, Alfredo, Gkouleli, Triantafylia, Heaney, Judith, Watters, Sarah, Bamford, Alasdair, Fidler, Katy, Navarro, Marisa, De Rossi, Anita, Palma, Paolo, Nastouli, Eleni, Rossi, Paolo, Giaquinto, Carlo, Rojo, Pablo and (EPIICAL) Consortium, (2020) The CARMA study: early infant antiretroviral therapy-timing impacts on total HIV-1 DNA quantitation 12 Years later. Journal of the Pediatric Infectious Diseases Society. pp. 1-7. ISSN 2048-7193

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Abstract

Background
Strategies aimed at antiretroviral therapy (ART)–free remission will target individuals with a limited viral reservoir. We investigated factors associated with low reservoir measured as total human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood mononuclear cells (PBMCs) in perinatal infection (PaHIV).

Methods
Children from 7 European centers in the Early Treated Perinatally HIV Infected Individuals: Improving Children’s Actual Life (EPIICAL) consortium who commenced ART aged <2 years, and remained suppressed (viral load [VL] <50 copies/mL) for >5 years were included. Total HIV-1 DNA was measured by quantitative polymerase chain reaction per million PBMCs. Factors associated with total HIV-1 DNA were analyzed using generalized additive models. Age, VL at ART initiation, and baseline CD4% effects were tested including smoothing splines to test nonlinear association.

Results
Forty PaHIV, 27 (67.5%) female 21 (52.5%) Black/Black African, had total HIV-1 DNA measured; median 12 (IQR, 7.3–15.4) years after ART initiation. Eleven had total HIV-1 DNA <10 copies/106 PBMCs. HIV-1 DNA levels were positively associated with age and VL at ART initiation, baseline CD4%, and Western blot antibody score. Age at ART initiation presented a linear association (coefficient = 0.10 ± 0.001, P ≤ .001), the effect of VL (coefficient = 0.35 ± 0.1, P ≤ .001) noticeable >6 logs. The effect of CD4% (coefficient = 0.03 ± 0.01, P = .049) was not maintained >40%.

Conclusions
In this PaHIV cohort, reduced total HIV-1 DNA levels were associated with younger age and lower VL at ART initiation. The impact of early-infant treatment on reservoir size persists after a decade of suppressive therapy.

Item Type: Article
Keywords: HIV reservoir, HIV-1, adolescents, children, early treated, viral suppression
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 05 Oct 2020 06:49
Last Modified: 05 Oct 2020 07:01
URI: http://sro.sussex.ac.uk/id/eprint/94116

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