The Berlin patient is presumed to be the only person cured from HIV-infection by hematopoietic stem cell transplantation (HSCT) from a homozygous CCR5-d32 unrelated donor. Attempts to reproduce cure by HSCT have failed because of either viral rebound or death due to the underlying malignancy. We here report a patient alive, well and negative for proviral DNA 900 days after allogeneic CCR5-d32 HSCT.
A 41y old HIV-infected male patient was diagnosed acute myeloid leukemia (AML, inv16, CBF-MYH11) in 01/2011. Since the diagnosis of HIV-infection in 10/2010 he had been treated with TDF/FTC+ DRV (01/2011 VL 44 cop/mL; CD4+ 474 cells/µl). To avoid interactions with chemotherapy DRV was switched to RAL in 03/2011. He achieved CR of the AML after 1 induction course (ICE) and received a 2nd induction and 3 consolidation courses according to AML-SG 07/04. In 09/2012 AML relapsed and he was treated with A-HAM and a 2nd cycle high-dose cytarabine. While in 2nd CR he received 8.74x10E6/kg unmodified peripheral blood stem cells from a female 10/10 CCR5-d32 DKMS-donor after conditioning with fludarabine and treosulfan in 02/2013. Before transplant HIV resistance analysis was performed for PR, RT, IN and viral tropism was determined.
There were no significant resistance mutations and the coreceptor-usage was predicted as R5-tropic (Sanger sequencing: FPR 44.5%; NGS: 0.14% X4 at 3.5% FPR; geno2pheno). The proviral DNA load was 29400 cop/mL and in the western blot all anticipated bands could be detected. During transplant and until today the patient remained on ART (since 06/2014 ABC/3TC/DTG) and the viral load remained undetectable in plasma and liquor. He had a 2nd relapse of AML in 06/2013 but re-entered molecular remission after a total of 8 courses of 5-azacytidine and 4 donor lymphocyte infusions. Concerning HIV, all collected samples were negative for proviral DNA by conventional and digital droplet PCR* in two different labs, namely PBMCs (06/2014, 01/2015* and 02/2015), rectal biopsy (04/2015) and bone marrow (08/2015*). Western blots from 06/2014 and 02/2015 showed incomplete patterns with fading bands.
Like in the Berlin patient, all tests from the Duesseldorf patient so far suggest that HIV may have been eradicated and that he may be the second individual cured from HIV by allogeneic CCR5-d32 HSCT. Further investigations will be performed before considering the discontinuation of ART.