BACKGROUND: A 34 yo Brazilian male received HIV diagnosis on October 11th, 2012. Baseline CD4+ T cell count was 372 cells/microliter and viral load (VL) was 20,221 cp/mL, suggesting chronic HIV infection. On December 12st, 2012 he started antiretroviral treatment with TDF/3TC/EFV maintaining VL below detection limits (BDL) since them. In 2016, he was enrolled in clinical trial NCT02961829 as one of five individuals under highly intensified ART (baseline ART+dolutegravir+maraviroc) and nicotinamide (500 mg twice daily) for 48 weeks. Nicotinamide (NAM) was chosen because of inhibition of immune exhaustion-related lymphocyte apoptosis related to its inhibitory effects on PARPs, and potential multiple mechanisms of antilatency such as Class III HDACs inhibition (NAM) and SUV39 Deacetylation (NAD). Maraviroc was also chosen due to potential HIV antilatency property.
METHODS: Viral DNA was measured as an estimate of the viral reservoir by published qPCR techniques. Antibody quantitation was performed using the Abbott ARCHITECT HIV Ag/Ab Combo assay (Abbott, IL, USA). Mathematical modelling performed according Conway et al., 2015.
RESULTS: Among 30 participating patients from NCT02961829, this study subject was the only experiencing viral load blips during experimental treatment, at weeks 16 (VL BDL with target detected) and 24 (56 cp/mL). Viral DNA showed low-level positivity in PBMCs and rectal biopsy at baseline and week 48. Antibody quantitation over time (RLU [S/CO] in duplicates) was 91.8 (baseline), 75.6 (week 12), 60.8 (w24), 56.8 (w36) and 58.0 (w48). In March 28th 2019, he underwent analytical treatment interruption (ATI). HIV Plasma VL performed every 3 weeks after ATI was BDL up to 57 weeks, and total HIV DNA on PBMCs was undetectable pre-ATI and 57 weeks post-ATI. EIA rapid test kit (TR DPP HIV 1/2 Bio-Manguinhos) on February 3rd 2020 was negative. Mathematical modelling (Conway et al., 2015) showed that the antiapoptotic and antiproliferative effects might improve clearance of productively infected cells, but only the additional contribution of the antilatency effect might induce long-term remission.
CONCLUSIONS: Although still an isolated case, this might represent the first long-term HIV remission without myeloablation/stem cell transplantation. Further analyses such as viral cultivation and sequential HIV antibody profile/detection are ongoing.