番茄社区

Thirty months later, and the so-called "London patient" is still in HIV remission following treatment interruption, researchers found.

The patient, who revealed himself to the New York Times on Monday as , had no detectable virus in plasma, cerebrospinal fluid (CSF), intestinal tissue, or lymphoid tissue, 30 months following HIV treatment interruption, reported Ravindra Gupta, PhD, of the University of Cambridge in England, and colleagues, in . The findings also were presented as a late-breaking poster at the virtual Conference on Retroviruses and Opportunistic Infections (CROI).

Castillejo, a.k.a. the "London patient," made international headlines at the 2019 CROI conference when his case report became the second case of HIV remission recorded after the famous Timothy Brown. The "London patient" received an allogeneic hematopoietic stem-cell transplantation with cells that did not express CCR5 (CCR5Δ32/Δ32), and reports of his progress at 18 months following treatment interruption were presented a year ago.

These were longer-term findings, where researchers examined samples from "diverse HIV reservoir sites," including viral load assays of plasma, semen, and CSF to detect HIV RNA, and gut biopsy samples and lymph-node tissue to detect cell-copy number and HIV DNA levels.

Using an assay with a detection limit of 1 copy/mL, HIV viral load was undetectable in plasma. They noted the patient has shown "somewhat slow CD4 reconstitution," with the CD4 count at 28 months at near pre-transplant levels (430 cells/μL).

"However, no opportunistic infections were reported and peripheral T-cell chimerism was maintained at 99%," they wrote.

Researchers also noted a "very low-level positive signal" for HIV DNA detected in CD4 memory cells at 28 months. Viral load in semen was undetectable in both plasma and cells, the authors said. CSF was within normal parameters at 28 months, while HIV DNA was negative in the rectum, cecum, sigmoid colon, and terminal ileum tissue samples at 22 months, the authors said.

They noted the importance of these tests, adding, "HIV-1 replication can occur in the CNS even during suppressive [antiretroviral therapy] and is frequently associated with symptoms and MRI abnormalities ... Intestinal lymphoid tissue is an important HIV reservoir and HIV-1 DNA was negative in gut biopsy samples."

In an , Jennifer Zerbato, PhD, and Sharon Lewin, MD, PhD, both of the University of Melbourne in Australia, noted two important points: namely that the low levels of HIV DNA were found "not intact, consistent with archival fragments that cannot replicate" and that based on a mathematical model, Gupta and colleagues calculated that the patient had "greater than 90% chimerism in circulating T cells," thus "the chance of future viral rebound while off ART [antiretroviral therapy] is negligible."

Zerbato and Lewin then discussed the many ways science has advanced since the "Berlin patient," and how one might better be able to hypothesize a patient is "cured" of HIV.

"We now know that most virus that persists on ART is defective and unable to replicate, and we are able to better quantify intact and defective virus with either near full-length sequencing or PCR-based assays," the editorialists wrote. "Therefore, a cure for HIV might be better defined as no intact virus, rather than no detectable virus."

But they added there needs to be "more than a handful of patients" cured of HIV to understand the duration of follow-up needed and the "likelihood of an unexpected late rebound in virus replication."

"The finding of no intact virus in both blood and tissue can be reassuring for a patient who might face great anxiety and uncertainty about whether and when viral rebound off ART might occur, which in other settings has been completely unpredictable," Zerbato and Lewin wrote.

But is this patient truly cured? Zerbato and Lewin concluded: "Only time will tell."