Cell-Associated HIV-1 DNA and RNA Decay Dynamics During Early Combination Antiretroviral Therapy in HIV-1-Infected Infants

Overview

Journal Clin Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2015 Aug 14

PMID 26270687

Citations 35

Authors

Priyanka Uprety

Ellen G Chadwick

Kaitlin Rainwater-Lovett

Carrie Ziemniak

Katherine Luzuriaga

Edmund V Capparelli

Gayane Yenokyan

Deborah Persaud

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Evaluation of HIV-1 DNA levels among adolescents living with perinatally acquired HIV-1 in Yaounde, Cameroon: A contribution to paediatric HIV cure research in Sub-Saharan Africa.

Kae A, Santoro M, Duca L, Ambe Chenwi C, Ngoufack Jagni Semengue E, Nka A J Virus Erad. 2024; 10(1):100367.

PMID: 38601701 PMC: 11004643. DOI: 10.1016/j.jve.2024.100367.

Age at ART initiation and proviral reservoir size in perinatal HIV-1 infection: considerations for ART-free remission.

Bekka S, Kelly K, Haaren M, Dhummakupt A, Persaud D Curr Opin HIV AIDS. 2024; 19(2):79-86.

PMID: 38169427 PMC: 11715321. DOI: 10.1097/COH.0000000000000839.

HIV-1 reservoir size after neonatal antiretroviral therapy and the potential to evaluate antiretroviral-therapy-free remission (IMPAACT P1115): a phase 1/2 proof-of-concept study.

Persaud D, Bryson Y, Nelson B, Tierney C, Cotton M, Coletti A Lancet HIV. 2023; 11(1):e20-e30.

PMID: 38061376 PMC: 11094801. DOI: 10.1016/S2352-3018(23)00236-9.

Microbiota in the oral cavity of school-age children with HIV who started antiretroviral therapy at young ages in South Africa.

Kuhn L, Wang T, Li F, Strehlau R, Tobin N, Violari A AIDS. 2023; 37(10):1583-1591.

PMID: 37199568 PMC: 10524539. DOI: 10.1097/QAD.0000000000003599.

HIV-1 remission and possible cure in a woman after haplo-cord blood transplant.

Hsu J, Van Besien K, Glesby M, Pahwa S, Coletti A, Warshaw M Cell. 2023; 186(6):1115-1126.e8.

PMID: 36931242 PMC: 10616809. DOI: 10.1016/j.cell.2023.02.030.

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