No single parameter reliably predicts post-treatment control (PTC) among HIV infected patients. However, both total HIV-1 DNA (tDNA) and cell-associated RNA (caRNA) have been individually associated to delayed viral rebound after ATI. We evaluated the predictive value of the combination of low DNA and caRNA in the identification of PTC.
The study is a two-step single arm multi-centric non-randomized prospective trial (NCT02590354). Major inclusion criteria in step 1 were: nadir CD4+ T-cell count >350cells/µl and plasma viral load (pVL) <50 cps/ml since ≥2 years. The size of the HIV reservoir was determined by droplet digital PCR measurement of tDNA and caRNA in peripheral blood mononuclear cells (PBMCs). In step 2, consenting participants with tDNA <66 cps/10[sup]6[/sup] PBMCs and caRNA <10 cps/10[sup]6[/sup] PBMCs underwent a leucapheresis prior ATI. cART was re-initiated whenever pVL, measured every other week, was >1,000 cps/ml at two consecutive measurements or at pVL > 10,000 cps/ml. tDNA and caRNA were measured at every visit during ATI as well as 4 and 12 weeks after cART re-initiation. Quantitative viral outgrowth assays (qVOA), viral release assays (VRA) and ultra-sensitive pVL were performed on pre-ATI samples. Associations between clinical, virological or immunological parameters and viral rebound dynamics were assessed with Kaplan-Meier estimates and Cox proportional hazard models.
Of the 114 participants, 37 (32.5%) met the viral reservoir criteria for ATI. Of them, 16 (14.0%) consented and underwent ATI. All 16 participants experienced rapid viral rebound two to eight weeks after ATI (figure), with 13/16 (81.3%) reporting an adverse event (AE) but none with serious AE. All participants suppressed viremia to levels below the limit of detection within 14 weeks of cART re-initiation. tDNA and caRNA returned to baseline levels within the 12 weeks after cART re-initiation. No correlations were observed between viral rebound dynamics and current or nadir CD4+ T-cell count, ultra-sensitive pVL, tDNA or caRNA, qVOA, VRA or any other clinical parameters.
We report on the first prospective study evaluating ATI in participants selected on the basis of a very small and transcriptionally silent HIV reservoir. No PTC was identified. ATI was shown to be safe, despite rapid viral rebound. The impact of ATI on the reservoir size after cART re-initiation was limited. None of the measured baseline parameters were predictive for viral rebound dynamics.