title: Challenges in detecting HIV persistence during potentially curative interventions: a study of the Berlin patient.
abstract: There is intense interest in developing curative interventions for HIV. How such a cure will be quantified and defined is not known. We applied a series of measurements of HIV persistence to the study of an HIV-infected adult who has exhibited evidence of cure after allogeneic hematopoietic stem cell transplant from a homozygous CCR5Δ32 donor. Samples from blood, spinal fluid, lymph node, and gut were analyzed in multiple laboratories using different approaches. No HIV DNA or RNA was detected in peripheral blood mononuclear cells (PBMC), spinal fluid, lymph node, or terminal ileum, and no replication-competent virus could be cultured from PBMCs. However, HIV RNA was detected in plasma (2 laboratories) and HIV DNA was detected in the rectum (1 laboratory) at levels considerably lower than those expected in ART-suppressed patients. It was not possible to obtain sequence data from plasma or gut, while an X4 sequence from PBMC did not match the pre-transplant sequence. HIV antibody levels were readily detectable but declined over time; T cell responses were largely absent. The occasional, low-level PCR signals raise the possibility that some HIV nucleic acid might persist, although they could also be false positives. Since HIV levels in well-treated individuals are near the limits of detection of current assays, more sensitive assays need to be developed and validated. The absence of recrudescent HIV replication and waning HIV-specific immune responses five years after withdrawal of treatment provide proof of a clinical cure.
authors.affiliation: San Francisco VA Medical Center and University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Yukl
authors.forename: Eli
authors.initials: E
authors.lastname: Boritz
authors.forename: Michael
authors.initials: M
authors.lastname: Busch
authors.forename: Christopher
authors.initials: C
authors.lastname: Bentsen
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chun
authors.forename: Daniel
authors.initials: D
authors.lastname: Douek
authors.forename: Evelyn
authors.initials: E
authors.lastname: Eisele
authors.forename: Ashley
authors.initials: A
authors.lastname: Haase
authors.forename: Ya-Chi
authors.initials: YC
authors.lastname: Ho
authors.forename: Gero
authors.initials: G
authors.lastname: Hütter
authors.forename: J Shawn
authors.initials: JS
authors.lastname: Justement
authors.forename: Sheila
authors.initials: S
authors.lastname: Keating
authors.forename: Tzong-Hae
authors.initials: TH
authors.lastname: Lee
authors.forename: Peilin
authors.initials: P
authors.lastname: Li
authors.forename: Danielle
authors.initials: D
authors.lastname: Murray
authors.forename: Sarah
authors.initials: S
authors.lastname: Palmer
authors.forename: Christopher
authors.initials: C
authors.lastname: Pilcher
authors.forename: Satish
authors.initials: S
authors.lastname: Pillai
authors.forename: Richard W
authors.initials: RW
authors.lastname: Price
authors.forename: Meghan
authors.initials: M
authors.lastname: Rothenberger
authors.forename: Timothy
authors.initials: T
authors.lastname: Schacker
authors.forename: Janet
authors.initials: J
authors.lastname: Siliciano
authors.forename: Robert
authors.initials: R
authors.lastname: Siliciano
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.forename: Matt
authors.initials: M
authors.lastname: Strain
authors.forename: Joseph
authors.initials: J
authors.lastname: Wong
authors.forename: Douglas
authors.initials: D
authors.lastname: Richman
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
mesh_terms: D000328:Adult; D064591:Allografts; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D004279:DNA, Viral / Q000097:blood* / Q000276:immunology; D006678:HIV; D015658:HIV Infections / Q000097:blood* / Q000134:cerebrospinal fluid / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D012367:RNA, Viral / Q000097:blood* / Q000276:immunology
chemical_list: D044966:Anti-Retroviral Agents; D000914:Antibodies, Viral; D004279:DNA, Viral; D012367:RNA, Viral