You are here
CCR5Δ32 SCT-INDUCED HIV REMISSION: TRACES OF HIV DNA BUT FADING IMMUNE REACTIVITY
Bjoern-Erik O. Jensen1, Dieter Häussinger1, Elena Knops2, Annemarie Wensing3, Javier Martinez-Picado4, Monique Nijhuis3, Maria Salgado4, Jacob D. Estes5, Nadine Lübke<
1Heinrich Heine University Düsseldorf, Düsseldorf, Germany,2University of Cologne, Cologne, Germany,3Utrecht University, Utrecht, Netherlands,4IrsiCaixa Institute for AIDS Research, Badalona, Spain,5Oregon Health and Sciences University, Portland, OR, USA,6University Hospital Erlangen, Erlangen, Germany,7University Medical Center Hamburg–Eppendorf, Hamburg, Germany,8University Hospital Hamburg–Eppendorf, Hamburg, Germany
To date only 3 patients have achieved long-term HIV-remission after analytic therapy interruption (ATI). Here we provide an update of the Duesseldorf patient (IciStem#19). This HIV-infected male patient (50y, heterozygous CCR5∆32 allele) received unmodified stem-cell transplantation (SCT) from a 10/10 matched CCR532/32 donor in Feb/13 for acute myeloid leukemia. At time of SCT complete western blot pattern was detected, proviral load was 1.45 log10cop/Mio PBMCs with R5-coreceptor-tropism. In Jun/13 complete remission was achieved by 5-Azacytidine and donor lymphocyte infusions (DLI) after a 2nd relapse. PBMC were negative for HIV-DNA by qPCR/ddPCR during relapse and thereafter. However, in T-cell subsets few positive signals were observed. qVOA/mVOA were negative. Biopsies: CSF Jul/14, rectum Apr/15+Mar/16, ileum Mar/16 and bone marrow Aug/15, and lymph nodes (LN) May/17 were HIV-DNA negative by PCR. In situ hybridization assays (RNAscope, DNAscope) detected few positive signals in LN. Moderate acute and mild chronic GvHD occurred after DLI but Tacrolimus could be finally stopped in Oct/17. He remained on ART with undetectable plasma VL until analytic therapy interruption (ATI) in Nov/18.
PBMC/tissues analysed by ddPCR/qPCR and in situ hybridization. T-cell responses with peptide stimulation assays. qVOA analysed on CD4+T-cells. Drug level assessment by liquid chromatography mass spectrometry.
After ATI no antiretrovirals could be detected in multiple plasma samples. In Jul/19 no HIV DNA was detected in CD45+ cells extracted from biopsies (duodenum/ileum/rectum). Neutrophils and IFN-1 responses in the GI tract were very low. CD4 T cells were abundant within GI tract follicular aggregates, RNAscope was negative, DNAscope showed few positive signals, but not clearly above the false detection rate. In Nov/19, 12 mo after ATI, HIV DNA was negative in naive, central memory, transitional memory, and effector/effector memory CD4 T-cells. qVOA in total CD4 T cells was also negative. Peptide stimulation assays showed CCR5-negative HIV-specific CTL with loss of recognition of RTYV9-specific and decrease of Gag-specific CTL after stopping immunosuppression. The absence of HIV-antigen is confirmed by fading humoral reactivity.
No viral rebound was observed for 14 months following ATI, 83 months after allogeneic CCR532 SCT. In depth analyses of the viral reservoir still showed traces of HIV DNA in LN and GI tract, not clearly representing infectious virus though, since all functional assays were negative. These results are compatible with sustained remission of HIV.