Background
Early ART initiation in children with perinatal HIV-1 infection reduces significantly the overall reservoir size. However, few studies assessed its impact on reservoir composition, particularly genetically intact, potentially replication-competent proviruses. From the ANRS-MIE-EP59 CLEAC study, we investigated whether early ART initiation affects reservoir intactness during childhood and adolescence.
Methods
The study included children (5-12 yrs) and adolescents (13-17 yrs) who initiated ART either early (<6 months of age) or late (≥24 months), reached initial virological success (pVL<400 cp/mL obtained ≤24 months after cART initiation) and had a pVL<50 cp/mL at the time of sampling. Intact and defective proviruses in PBMCs were quantified using IPDA, and compared according early or late ART initiation groups, using Chi-square or Fisher’s tests for categorial variable, and Mann-Whitney test for continuous variables. Crude and adjusted odds-ratio were estimated by logistic regression.
Results
When detectable, intact provirus levels were higher in late- compared with early-treated individuals (median 2.00 vs 1.69 log₁₀ copies/10⁶ PBMCs; p=0.025), although this difference was not significant when children and adolescents were analyzed separately (Fig. 1a). Similarly defective provirus levels were significantly higher in late-treated participants (2.98 vs 2.31 log₁₀ copies/10⁶ PBMCs; p<0.001). In children, the proportion with detectable intact proviruses was higher in late-treated (12/17) than in early-treated (9/23): crude OR=3.73 [1.02–15.4]; p=0.049; Fig 1b). This proportion increased with normalized cumulative viremia over the 2 previous years: crude OR=1,1 [1.02–1.25]; p<0.01. After adjustment for both variables, the association with cumulative viremia remained significant (adjOR: 1.10 [1.03–1.24]; p<0.01); but it was lower and not significant with early versus late cART initiation (adjOR: 2.31 [0.49–11.24]; p=0.28). In adolescents, intact provirus detection was not associated with timing of ART initiation (3/6 vs 8/15; p=1.00, Fig. 1b).
Conclusions
Early ART initiation after perinatal HIV infection is associated with a markedly reduced pool of genetically intact proviruses, although later loss of viral control may partly reduce these benefits. Importantly, in real-life clinical settings, some early-treated children reach undetectable levels of intact HIV DNA, suggesting that they may represent promising candidates for future HIV cure strategies.
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