Kaitlin Rainwater-Lovett1, Katherine Luzuriaga, Deborah Persaud. 1. aDepartment of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland bProgram in Molecular Medicine, Department of Pediatrics, and Center for Clinical and Translational Science, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Abstract
PURPOSE OF REVIEW: A single case of sustained HIV control in the absence of antiretroviral therapy or HIV-specific immune responses ensued following 18 months of combination antiretroviral therapy initiated at 30 h of age in a perinatally HIV-infected child (the Mississippi child). This case provides proof-of-concept that delay in HIV viremic rebound may ensue following very early treatment (VET) in perinatal infection, likely through marked reduction of latent replication-competent HIV reservoirs. RECENT FINDINGS: The latent HIV reservoir remains the critical barrier to remission. Several studies indicate that the earlier effective combination antiretroviral therapy is initiated, the smaller the size of the HIV reservoir. The unique ability of perinatally infected neonates to initiate VET at the time of birth maximizes the potential benefits of limiting latent reservoir size and permitting reservoir decay, likely lengthening the duration of remission and limiting the capacity for re-establishment of viremia. SUMMARY: This article covers the rationale and feasibility of VET to achieve sustained virologic remission in perinatal infection. Recent studies highlighting the effects of VET on biomarkers of HIV persistence in perinatal HIV infection are reviewed as well as implications and challenges for cure research in pediatric populations.
PURPOSE OF REVIEW: A single case of sustained HIV control in the absence of antiretroviral therapy or HIV-specific immune responses ensued following 18 months of combination antiretroviral therapy initiated at 30 h of age in a perinatally HIV-infectedchild (the Mississippi child). This case provides proof-of-concept that delay in HIV viremic rebound may ensue following very early treatment (VET) in perinatal infection, likely through marked reduction of latent replication-competent HIV reservoirs. RECENT FINDINGS: The latent HIV reservoir remains the critical barrier to remission. Several studies indicate that the earlier effective combination antiretroviral therapy is initiated, the smaller the size of the HIV reservoir. The unique ability of perinatally infected neonates to initiate VET at the time of birth maximizes the potential benefits of limiting latent reservoir size and permitting reservoir decay, likely lengthening the duration of remission and limiting the capacity for re-establishment of viremia. SUMMARY: This article covers the rationale and feasibility of VET to achieve sustained virologic remission in perinatal infection. Recent studies highlighting the effects of VET on biomarkers of HIV persistence in perinatal HIV infection are reviewed as well as implications and challenges for cure research in pediatric populations.
Authors: Christine Katlama; Steven G Deeks; Brigitte Autran; Javier Martinez-Picado; Jan van Lunzen; Christine Rouzioux; Michael Miller; Stefano Vella; Joern E Schmitz; Jeffrey Ahlers; Douglas D Richman; Rafick P Sekaly Journal: Lancet Date: 2013-03-29 Impact factor: 79.321
Authors: Hiroyu Hatano; Ma Somsouk; Elizabeth Sinclair; Kara Harvill; Lee Gilman; Michelle Cohen; Rebecca Hoh; Peter W Hunt; Jeffrey N Martin; Joseph K Wong; Steven G Deeks; Steven A Yukl Journal: AIDS Date: 2013-09-10 Impact factor: 4.177
Authors: Deborah Persaud; Hannah Gay; Carrie Ziemniak; Ya Hui Chen; Michael Piatak; Tae-Wook Chun; Matthew Strain; Douglas Richman; Katherine Luzuriaga Journal: N Engl J Med Date: 2013-10-23 Impact factor: 91.245
Authors: Timothy J Henrich; Zixin Hu; Jonathan Z Li; Gaia Sciaranghella; Michael P Busch; Sheila M Keating; Sebastien Gallien; Nina H Lin; Francoise F Giguel; Laura Lavoie; Vincent T Ho; Philippe Armand; Robert J Soiffer; Manish Sagar; Ann S Lacasce; Daniel R Kuritzkes Journal: J Infect Dis Date: 2013-03-04 Impact factor: 5.226
Authors: Mark F Cotton; Avy Violari; Kennedy Otwombe; Ravindre Panchia; Els Dobbels; Helena Rabie; Deirdre Josipovic; Afaaf Liberty; Erica Lazarus; Steve Innes; Anita Janse van Rensburg; Wilma Pelser; Handre Truter; Shabir A Madhi; Edward Handelsman; Patrick Jean-Philippe; James A McIntyre; Diana M Gibb; Abdel G Babiker Journal: Lancet Date: 2013-11-09 Impact factor: 79.321
Authors: Ya-Chi Ho; Liang Shan; Nina N Hosmane; Jeffrey Wang; Sarah B Laskey; Daniel I S Rosenbloom; Jun Lai; Joel N Blankson; Janet D Siliciano; Robert F Siliciano Journal: Cell Date: 2013-10-24 Impact factor: 41.582
Authors: Steven A Yukl; Eli Boritz; Michael Busch; Christopher Bentsen; Tae-Wook Chun; Daniel Douek; Evelyn Eisele; Ashley Haase; Ya-Chi Ho; Gero Hütter; J Shawn Justement; Sheila Keating; Tzong-Hae Lee; Peilin Li; Danielle Murray; Sarah Palmer; Christopher Pilcher; Satish Pillai; Richard W Price; Meghan Rothenberger; Timothy Schacker; Janet Siliciano; Robert Siliciano; Elizabeth Sinclair; Matt Strain; Joseph Wong; Douglas Richman; Steven G Deeks Journal: PLoS Pathog Date: 2013-05-09 Impact factor: 6.823
Authors: Susanne Eriksson; Erin H Graf; Viktor Dahl; Matthew C Strain; Steven A Yukl; Elena S Lysenko; Ronald J Bosch; Jun Lai; Stanley Chioma; Fatemeh Emad; Mohamed Abdel-Mohsen; Rebecca Hoh; Frederick Hecht; Peter Hunt; Ma Somsouk; Joseph Wong; Rowena Johnston; Robert F Siliciano; Douglas D Richman; Una O'Doherty; Sarah Palmer; Steven G Deeks; Janet D Siliciano Journal: PLoS Pathog Date: 2013-02-14 Impact factor: 6.823
Authors: Catherine G Sutcliffe; Janneke H van Dijk; Francis Hamangaba; Felix Mayani; William J Moss Journal: PLoS One Date: 2014-01-24 Impact factor: 3.240
Authors: Pilar Garcia-Broncano; Shivaali Maddali; Kevin B Einkauf; Chenyang Jiang; Ce Gao; Joshua Chevalier; Fatema Z Chowdhury; Kenneth Maswabi; Gbolahan Ajibola; Sikhulile Moyo; Terence Mohammed; Thabani Ncube; Joseph Makhema; Patrick Jean-Philippe; Xu G Yu; Kathleen M Powis; Shahin Lockman; Daniel R Kuritzkes; Roger Shapiro; Mathias Lichterfeld Journal: Sci Transl Med Date: 2019-11-27 Impact factor: 17.956