Cell-Associated HIV-1 DNA and RNA Decay Dynamics During Early Combination Antiretroviral Therapy in HIV-1-Infected Infants
Department of Pediatrics, Division of Immunology/Infectious Disease
Immunoprophylaxis and Therapy | Infectious Disease | Pediatrics | Therapeutics | Virus Diseases
BACKGROUND: The decay of human immunodeficiency virus type 1 (HIV-1)-infected cells during early combination antiretroviral therapy (cART) in infected infants is not defined.
METHODS: HIV-1 DNA, including 2-long terminal repeat (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.
RESULTS: The median HIV-1 DNA concentration before cART at a median age of 2 months was 3.2 log10 copies per million PBMC. With cART, the average estimated patient-specific change in HIV-1 DNA concentrations was -0.040 log10/week (95% confidence interval [CI], -.05, -.03) between 0 and 24 weeks and -0.017 log10/week between 24 and 48 weeks (95% CI, -.024, -.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.
CONCLUSIONS: By 2 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.
HIV-1 DNA decay, HIV-1 RNA decay, early combination antiretroviral therapy, perinatal HIV-1 infection, reservoir
DOI of Published Version
Clin Infect Dis. 2015 Dec 15;61(12):1862-70. doi: 10.1093/cid/civ688. Epub 2015 Aug 13. Link to article on publisher's site
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Uprety, Priyanka; Chadwick, Ellen Gould; Rainwater-Lovett, Kaitlin; Ziemniak, Carrie; Luzuriaga, Katherine; Capparelli, Edmund V.; Yenokyan, Gayane; and Persaud, Deborah, "Cell-Associated HIV-1 DNA and RNA Decay Dynamics During Early Combination Antiretroviral Therapy in HIV-1-Infected Infants" (2015). Pediatric Publications and Presentations. 59.