Evidence for HIV-1 Cure in the ‘London Patient’: a case report

Abstract

Background The ‘London Patient’ (IciS-36) underwent allogeneic stem cell transplantation with cells lacking the expression of CCR5 (CCR5Δ32/Δ32) and remission was reported at 18 months. Here we present longer term data including sampling from diverse HIV-1 reservoir sites. Methods Ultra-sensitive plasma, semen and cerebrospinal fluid (CSF) viral load assays were used to detect HIV-1 RNA. In gut biopsies and lymph node tissue cell-copy number, total HIV-1 DNA levels were quantified in multiple replicates using droplet digital PCR (ddPCR) and real time qPCR. Furthermore, presence of intact proviral DNA was analyzed using multiplex ddPCR targeting the packaging signal (psi) and env. Intracellular cytokine staining was used to measure HIV-1 specific T cell responses. Detuned and low avidity antibody assays were used to measure the humoral response to HIV-1. We predicted the probability of rebound using a previously-developed mathematical model and inference approach. Findings HIV-1 viral load in plasma has remained undetectable using an assay with detection limit of 1 copy/ml up to 29 months. The most recent CD4 count was 430 cells per µL (20.3%). There was a very low level positive signal for HIV-1 DNA in peripheral CD4 memory cells. Semen viral load was undetectable in both plasma (LLD <12 copies/ml) and cells (LLD 10 copies/million cells). CSF was within normal parameters with HIV-1 RNA below detection limit (LLD 1 copy/ml). HIV-1 DNA by ddPCR was negative in rectum, caecum, sigmoid and terminal ileum. Lymph node tissue from axilla was positive for LTR and env at around 30 copies/million cells, negative for packaging signal and integrase, and negative by the intact proviral DNA assay (IPDA). HIV-1 specific CD4 and CD8 T cell responses have remained absent through to 2.5 years. Low avidity Env antibodies have continued to decline. Mathematical modelling suggests that probability of cure is 98% in the context of 80% donor chimerism in total HIV target cells and >99% probability of cure with 90% donor chimerism. Interpretation The ‘London Patient’ has been in HIV remission for 29 months with no detectable replication-competent virus in blood, CSF, intestinal tissue, or lymphoid tissue. Donor chimerism has been maintained at 99% in peripheral T cells. We conclude that this represents HIV-1 cure.