Uprety P, Chadwick EG, Rainwater-Lovett K, Ziemniak C, Luzuriaga K, Capparelli EV, Yenokyan G, Persaud D.
Clinical Infectious Disease
Pages / Chapters
pii: civ688. [Epub ahead of print]
The decay of HIV-1-infected cells during early combination antiretroviral therapy (cART) in infected infants is not defined.
HIV-1 DNA, including 2-LTR circles, and multiply-spliced (ms-) and unspliced (us-) HIV-1 RNA concentrations were measured at 0, 24, 48, and 96 weeks of cART in infants from the IMPAACT P1030 trial receiving lopinavir-ritonavir-based cART. The ratio of HIV-1 DNA concentrations to replication-competent genomes was also estimated. Linear mixed effects models with random intercept and linear splines were used to estimate patient-specific decay kinetics of HIV-1 DNA.
The median HIV-1 DNA concentration before cART at a median age of two months was 3.2 log10 copies per million PBMC. With cART, the average estimated patient-specific change in HIV-1- DNA concentrations was -0.04 log10/week (95%CI: -0.05, -0.03) between 0 and 24 weeks and -0.017 log10/week between 24 and 48 weeks (95%CI: -0.024, -0.01). 2-LTR circles decreased with cART but remained detectable through 96 weeks. Pre-cART HIV-1 DNA concentration was correlated with time to undetectable plasma viral load and post-cART HIV-1 DNA at 96 weeks; although HIV-1 DNA concentrations exceeded replication-competent HIV-1 genomes by 148-fold. Almost all infants had ms- and usRNA detected pre-cART, with 75% having usRNA through 96 weeks of cART.
By two months of age, a large pool of HIV-1-infected cells is established in perinatal infection, which influences time to undetectable viral load and reservoir size. This has implications for informing novel approaches aimed at early restriction of HIV-1 reservoirs to enable virologic remission and cure.