Evidence for HIV-1 cure after CCR5 Delta 32/Delta 32 allogeneic haemopoietic stem-cell transplantation 30 months post analytical treatment interruption: a case report
| Autor: | Gupta, RK, Peppa, D, Hill, AL, Galvez, C, Salgado, M, Pace, M, McCoy, LE, Griffith, SA, Thornhill, J, Alrubayyi, A, Huyveneers, LEP, Nastouli, E, Grant, P, Edwards, SG, Innes, AJ, Frater, J, Nijhuis, M, Wensing, AMJ, Martinez-Picado, J, Olavarria, E |
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| Rok vydání: | 2020 |
| Zdroj: | Lancet HIV r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol instname |
| ISSN: | 2405-4704 |
| Popis: | Background The London patient (participant 36 in the IciStem cohort) underwent allogeneic stem-cell transplantation with cells that did not express CCR5 (CCR5 Delta 32/Delta 32); remission was reported at 18 months after analytical treatment interruption (ATI). Here, we present longer term data for this patient (up to 30 months after ATI), including sampling from diverse HIV-1 reservoir sites. Methods We used ultrasensitive viral load assays of plasma, semen, and cerebrospinal fluid (CSF) samples to detect HIV-1 RNA. In gut biopsy samples and lymph-node tissue, cell-copy number and total HIV-1 DNA levels were quantified in multiple replicates, using droplet digital PCR (ddPCR) and quantitative real-time PCR. We also analysed the presence of intact proviral DNA using multiplex ddPCR targeting the packaging signal (psi) and envelope (env). We did intracellular cytokine staining to measure HIV-1-specific T-cell responses. We used low-sensitive and low-avidity antibody assays to measure the humoral response to HIV-1. We predicted the probability of rebound using a mathematical model and inference approach. Findings HIV-1 viral load in plasma remained undetectable in the London patient up to 30 months (last tested on March 4, 2020), using an assay with a detection limit of 1 copy per mL. The patient's CD4 count was 430 cells per mu L (23.5% of total T cells) at 28 months. A very low-level positive signal for HIV-1 DNA was recorded in peripheral CD4 memory cells at 28 months. The viral load in semen was undetectable in both plasma (lower limit of detection [LLD] |
| Databáze: | OpenAIRE |
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