title: Autologous neutralizing antibody to human immunodeficiency virus-1 and replication-competent virus recovered from CD4+ T-cell reservoirs in pediatric HIV-1-infected patients on HAART.
abstract: A patient's ability to produce autologous neutralizing antibody (ANAB) to current and past HIV isolates correlates with reduced disease progression and protects against maternal-fetal transmission. Little is known about the effects of prolonged viral suppression on the ANAB response in pediatric HIV-infected patients receiving HAART because the virus is hard to isolate, except by special methods. We therefore assessed ANAB to pre-HAART PBMC virus isolates and post-HAART replication-competent virus (RCV) isolates recovered from latent CD4(+) T-cell reservoirs in perinatally HIV-infected children by using a PBMC-based assay and 90% neutralization titers. We studied two infants and three children before and after HAART. At the time of RCV isolation (n = 4), plasma HIV RNA was <50 copies/ml. At baseline, four of five children had detectable ANAB titers to concurrent pre-HAART virus isolates. Although ANAB was detected in all subjects at several time points despite prolonged HAART and undetectable viremia, the response was variable. ANAB titers to concurrent post-HAART RCV and earlier pre-HAART plasma were present in 3 children suggesting prior exposure to this virus. Post-HAART RCV isolates had reduced replication kinetics in vitro compared to pre-HAART viruses. The presence of ANAB over time suggests that low levels of viral replication may still be ongoing despite HAART. The observation of baseline ANAB activity with earlier plasma against a later RCV suggests that the "latent" reservoir may be established early in life before HAART.
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at UCLA, Mattel Children's Hospital UCLA, Los Angeles, California 90095, USA. nching@mednet.ucla.edu
authors.forename: Natascha
authors.initials: N
authors.lastname: Ching
authors.forename: Karin A
authors.initials: KA
authors.lastname: Nielsen-Saines
authors.forename: Jaime G
authors.initials: JG
authors.lastname: Deville
authors.forename: Lian S
authors.initials: LS
authors.lastname: Wei
authors.forename: Eileen
authors.initials: E
authors.lastname: Garratty
authors.forename: Yvonne J
authors.initials: YJ
authors.lastname: Bryson
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000097:blood*; D023241:Antiretroviral Therapy, Highly Active / Q000706:statistics & numerical data*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D006801:Humans; D007223:Infant; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D018894:Reverse Transcriptase Inhibitors
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