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March 10, 2020
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‘Cure is possible’: London patient remains in HIV remission 1 year later

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The London patient, whose case was first reported 1 year ago at CROI 2019, has remained in HIV-1 remission for 30 months, according to findings from CROI 2020.

“We believe these findings probably represent the second recorded HIV-1 cure after CCR5-delta 32 allogeneic hematopoietic stem cell transplantation (allo-HSCT), with evidence of residual low-level HIV-1 DNA,” the researchers wrote in The Lancet, where the study was also published.

In 2019, researchers announced that an unidentified man from London had undergone allo-HSCT for Hodgkin’s lymphoma and remained in HIV remission for at least 18 months after stopping HIV treatment.

One year later, at CROI 2020, Ravindra K. Gupta, PhD, from the University College London, and colleagues presented follow-up data. The researchers used ultrasensitive viral load assays of plasma, semen and cerebrospinal fluid (CSF) samples to find HIV-1 RNA in the London patient. They also used multiplex droplet digital PCR targeting the packaging signal and envelope to look for the presence of intact proviral DNA.

Gupta and colleagues found that the HIV-1 viral load in plasma remained undetectable in the London patient through testing on March 4, 2020 — up to 30 months after analytical treatment interruption of antiretroviral therapy.

Researchers reported that the patient’s CD4 count was 430 cells/µL (23.5% of total T cells) at 28 months; a very low-level positive signal for HIV-1 DNA was found in peripheral CD4 memory cells at the same time point. HIV-1-specific CD4 and CD8 T-cell responses remained absent at 27 months. Additionally, the viral load in semen was undetectable in both plasma (lower limit of detection [LLD], <12 copies per mL) and cells (LLD, 10 copies per 10 cells) at 21 months and CSF was within normal parameters at 25 months, with HIV-1 RNA was below the detection limit (LLD, 1 copy per mL).

Using mathematical modeling, Gupta and colleagues believe that the London patient’s probability of remission for life — a cure — is 98% in the context of 80% donor chimerism in total HIV target cells and a greater than 99% probability of remission for life with 90% donor chimerism.

“Cure is possible with reduced-intensity chemotherapy regimens and without irradiation,” Gupta told Healio. “We do still see positive HIV antibodies in cure because the immune system has long-term memory. There is no sign of active virus, although we did see fossils of HIV DNA in cells.”

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In an accompanying comment, Jennifer M. Zerbato, PhD, a research fellow at the Peter Doherty Institute for Infection and Immunity at the University of Melbourne and Royal Melbourne Hospital, and Sharon R. Lewin, PhD, director of the Peter Doherty Institute, wrote that these findings can reassure a patient facing anxiety and uncertainty about whether or not, and when, viral rebound in the absence of ART may occur — something that has been “completely unpredictable” in other settings.

“In view of the many cells sampled in this case, and the absence of any intact virus, is the London patient truly cured?” Zerbato and Lewin wrote. “The additional data provided in this follow-up case report is certainly exciting and encouraging but, in the end, only time will tell.” – by Caitlyn Stulpin

References

Gupta RK, et al. Abstract 346LB. Presented at: Conference on Retroviruses and Opportunistic Infections; March 8-11, 2020; Boston.

Gupta RK, et al. Lancet HIV. 2020;doi:10.1016/ S2352-3018(20)30069-2.

Zerbato JM, et al. Lancet HIV. 2020;doi:10.1016/ S2352-3018(20)30069-2.

Disclosure: Gupta, Lewin and Zerbato reports no relevant financial disclosures.