TY - JOUR
T1 - Cell-Associated HIV-1 DNA and RNA Decay Dynamics during Early Combination Antiretroviral Therapy in HIV-1-Infected Infants
AU - Uprety, Priyanka
AU - Chadwick, Ellen G.
AU - Rainwater-Lovett, Kaitlin
AU - Ziemniak, Carrie
AU - Luzuriaga, Katherine
AU - Capparelli, Edmund V.
AU - Yenokyan, Gayane
AU - Persaud, Deborah
N1 - Publisher Copyright:
© 2015 The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
PY - 2015/12/15
Y1 - 2015/12/15
N2 - 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.
AB - 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.
KW - HIV-1 DNA decay
KW - HIV-1 RNA decay
KW - early combination antiretroviral therapy
KW - perinatal HIV-1 infection
KW - reservoir
UR - http://www.scopus.com/inward/record.url?scp=84954031399&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84954031399&partnerID=8YFLogxK
U2 - 10.1093/cid/civ688
DO - 10.1093/cid/civ688
M3 - Article
C2 - 26270687
AN - SCOPUS:84954031399
SN - 1058-4838
VL - 61
SP - 1862
EP - 1870
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 12
ER -