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  AIDS 2022
July 29 - Aug 2
24th Intl AIDS Conference
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Exceptional Post-Treatment HIV Control in an Acute
HIV-Infected Woman During More than 15 Yearsbr
Exceptional post-treatment control associated with strong
NK and gamma delta ? cytotoxic T cells

  AIDS 2022 July 29 - Aug 1 Montrealbr
N. Climent
N. Climent * (1,2), J. Ambrosioni (1,2), T. González (1,2), M. Casadella (3), M. Noguera (3), R. Paredes (3), M. Plana (1,2), J. Mallolas (1,2), J. Alcamí (1,4,2), S. Sánchez-Palomino (1,2), J.M. Miró (1,2)
(1) Hospital Clinic-IDIBAPS/University of Barcelona, HIV Unit, Barcelona, Spain, (2) CIBER of Infectious Diseases (CIBERINFEC), Madrid, Spain, (3) IrsiCaixa AIDS Research Institute. Hospital Universitari Germans Trias i Pujol, Badalona, Spain, (4) Instituto de Salud Carlos III (ISCIII)., Madrid, Spain
Program Abstract
Although ART is effective in suppressing viral replication, HIV persists in reservoirs and rebounds after stopping therapy. However, there are few patients, such as post-treatment controllers (PTC), who are able to maintain viral loads below detection limits without ART, being a realistic model for the HIV-functional-cure. We describe the mechanisms of control of an exceptional PTC (>15 years).
METHODS: A 59-year woman with sexually-acquired acute HIV-infection was included in the 'Immune-mediated PHI trial´ (NCT00979706), involving several interventions: short course of low doses of CsA, IL-2, GM-CSF and Peg-a-IFN followed by analytical STI. Virological studies were performed: total and integrated HIV-1 DNA in CD4+ T-cells and rectal tissue, viral outgrowth assay (qVOA), HIV-1 infectivity in PBMC and CD4+ T-cells cultures and viral inhibitory activity (VIA) of autologous CD4+T-cells with NK and CD8+ T-cells. NK and T-cell phenotype was determined by flow-cytometry.HLA class I, Î?32CCR5 and NKG2C alleles were genotyped.
RESULTS: After antiretroviral and immunomodulatory treatment, the patient maintained undetectable viral load in plasma for 15 years. HIV-1 subtype was CFR_02AG, R5-tropic. We found a pronounced and progressive fall of the viral reservoir (VR): total HIV-DNA (from 4573.50 to 95.33 copies/106 CD4+T-cells) and integrated proviral DNA (from 85.37 to 5.25 copies/106 CD4+T-cells).VR in rectal biopsy was 3 HIV DNA total copies/106 cells and qVOA detected 1.61 UIMP at year 9. VIA assay showed strong inhibition of in vitro replication in co-cultures with autologous NK-cells or CD8+T-cells at 1:2 ratio (75% and 62%, respectively). Co-cultures with NK and CD8+T-cells resulted in 93% inhibition of HIV-replication. Higher levels of both NKG2C+-memory-like NK-cells and NKG2C+Ï?E?+T-cells than referenced data from untreated normal HIV-infected progressors were detected (46.2% versus 24.0% and 64.9% versus 19.7%, respectively). The patient has A*29:01/A*29:01, B*44:03/B*44:03, C*16:01/C*16:01 HLA-I, wt/wt CCR5 and wt/wt NKG2C alleles.
CONCLUSIONS: We describe the case of functional cure in a 59-years-old woman treated during PHI that has maintained undetectable viral load for 15 years without ART. Replication-competent HIV-1 could be isolated by qVOA. NKG2C+-memory-like NK-cells and Ï?E?+CD8+T-cells contribute to the control of viral-replication and functional-cure observed. Strategies able to expand these cells could help to achieve HIV-functional-cure.
Oral Presentation