title: Anti-HIV Antibody Responses and the HIV Reservoir Size during Antiretroviral Therapy.
abstract: BACKGROUND
  A major challenge to HIV eradication strategies is the lack of an accurate measurement of the total burden of replication-competent HIV (the "reservoir"). We assessed the association of anti-HIV antibody responses and the estimated size of the reservoir during antiretroviral therapy (ART).
  
  
  METHODS
  We evaluated anti-HIV antibody profiles using luciferase immunoprecipitation systems (LIPS) assay in relation to several blood-based HIV reservoir measures: total and 2-LTR DNA (rtPCR or droplet digital PCR); integrated DNA (Alu PCR); unspliced RNA (rtPCR), multiply-spliced RNA (TILDA), residual plasma HIV RNA (single copy PCR), and replication-competent virus (outgrowth assay). We also assessed total HIV DNA and RNA in gut-associated lymphoid tissue (rtPCR). Spearman correlations and linear regressions were performed using log-transformed blood- or tissue-based reservoir measurements as predictors and log-transformed antibody levels as outcome variables.
  
  
  RESULTS
  Among 51 chronically HIV-infected ART-suppressed participants (median age = 57, nadir CD4+ count = 196 cells/mm3, ART duration = 9 years), the most statistically significant associations were between antibody responses to integrase and HIV RNA in gut-associated lymphoid tissue (1.17 fold-increase per two-fold RNA increase, P = 0.004) and between antibody responses to matrix and integrated HIV DNA in resting CD4+ T cells (0.35 fold-decrease per two-fold DNA increase, P = 0.003). However, these associations were not statistically significant after a stringent Bonferroni-adjustment of P<0.00045. Multivariate models including age and duration of ART did not markedly alter results.
  
  
  CONCLUSIONS
  Our findings suggest that anti-HIV antibody responses may reflect the size of the HIV reservoir during chronic treated HIV disease, possibly via antigen recognition in reservoir sites. Larger, prospective studies are needed to validate the utility of antibody levels as a measure of the total body burden of HIV during treatment.
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, United States of America.
authors.forename: Sulggi A
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Bacchetti
authors.affiliation: CR-CHUM and Department of Microbiology, Infectious Diseases, and Immunology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chomont
authors.affiliation: CR-CHUM and Department of Microbiology, Infectious Diseases, and Immunology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Remi
authors.initials: R
authors.lastname: Fromentin
authors.affiliation: The Peter Doherty for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, VIC, Australia.|Department of Infectious Diseases, Monash University and Alfred Hospital, Melbourne, VIC, Australia.
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
authors.forename: Una
authors.initials: U
authors.lastname: O'Doherty
authors.affiliation: Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Palmer
authors.affiliation: Departments of Medicine and Pathology, University of California San Diego, La Jolla, California, United States of America, Veterans Affairs San Diego Healthcare System, San Diego, CA, United States of America.
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Richman
authors.affiliation: Department of Medicine Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
authors.forename: Janet D
authors.initials: JD
authors.lastname: Siliciano
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, United States of America.|Veterans Affairs San Francisco Healthcare System, San Francisco, CA, United States of America.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Yukl
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, United States of America.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.affiliation: Dental Clinical Research Core, National Institute of Dental and Craniofacial Research, Bethesda, MD, United States of America.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Burbelo
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D004279:DNA, Viral / Q000187:drug effects / Q000235:genetics; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D019427:HIV Integrase / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000276:immunology / Q000821:virology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012326:RNA Splicing; D012367:RNA, Viral / Q000187:drug effects / Q000235:genetics; D019562:Viral Load / Q000187:drug effects* / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D015483:HIV Antibodies; D012367:RNA, Viral; D019427:HIV Integrase