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The CARMA Study: Early Infant Antiretroviral Therapy-Timing Impacts on Total HIV-1 DNA Quantitation 12 Years Later
Caroline Foster1, Sara Domínguez-Rodríguez2, Alfredo Tagarro2
1Imperial College Healthcare NHS Trust, London, United Kingdom.
Insights
Early treatment for perinatally HIV-1 infected (PaHIV) individuals is linked to smaller viral reservoirs. Younger age and lower viral load at antiretroviral therapy (ART) initiation are key factors in achieving reduced HIV-1 DNA levels.
Area of Science:
- Virology
- Immunology
- Pediatric Infectious Diseases
Background:
- Strategies for antiretroviral therapy (ART)-free remission in HIV-1 focus on reducing viral reservoirs.
- Investigating factors associated with low total human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood mononuclear cells (PBMCs) is crucial for perinatal HIV infection (PaHIV).
Purpose of the Study:
- To identify factors associated with a reduced viral reservoir, measured as total HIV-1 DNA in PBMCs, among individuals with perinatal HIV infection (PaHIV).
Main Methods:
- The study included 40 PaHIV from the EPIICAL consortium, who started ART before age 2 and maintained viral suppression for over 5 years.
- Total HIV-1 DNA was quantified using PCR in PBMCs. Generalized additive models analyzed associations with age, viral load (VL) at ART initiation, and baseline CD4%.
- Nonlinear associations were explored using smoothing splines for age, VL, and CD4% effects.
Main Results:
- Lower total HIV-1 DNA levels (<10 copies/10^6 PBMCs) were observed in 11 participants.
- HIV-1 DNA levels positively correlated with age at ART initiation, VL at initiation, baseline CD4%, and Western blot antibody score.
- A linear association was found between age at ART initiation and HIV-1 DNA (coefficient = 0.10 ± 0.001, P ≤ .001). VL effects were significant above 6 logs (coefficient = 0.35 ± 0.1, P ≤ .001).
Conclusions:
- Reduced total HIV-1 DNA levels in PaHIV are associated with younger age and lower VL at the initiation of ART.
- Early infant treatment demonstrates a lasting impact on viral reservoir size, even after a decade of suppressive ART.
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.
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