In prior studies treatment of ART-suppressed individuals with pegylated interferon alpha (pIFNα) resulted in a decrease in PBMC-associated integrated HIV DNA. We sought to confirm the effect of pIFNα on latent HIV by measuring inducible HIV expression from CD4 cells isolated from chronically infected, ART-suppressed individuals receiving pIFNα-2b immunotherapy in a randomized clinical trial (NCT02227277).
We enrolled 54 HIV-infected individuals receiving suppressive ART (HIV VL < 50 copies/ml) and with CD4 count > 450/μl who were randomized 1:1:1 to 3 treatment arms: 1.,1 μg/kg of pIFNα-2b (Pegintron, Merck) for 20 weeks, with ART interruption (start at week 4, resume ART upon confirmed VL > 50 copies/μl or at week 20) 2.,1 μg/kg of pIFNα-2b added to ART 3.,ART only (control) All subjects were sampled at baseline and week 20. CD4+ T cells were isolated from PBMC and cultured (2-10 replicates) for 16-hour with medium or PMA + Ionomycin. HIV p24 production was measured in cell pellets using single molecule array (SIMOA) with a limit of quantification (LOQ) of 7 fg/106 cells. Analysis approach: modified intention to treat. Measurements < LOQ were censored at the LOQ; p24 levels were log-transformed. The changes in PMA-induced SIMOA HIV p24 levels at endpoint from baseline were compared between first two treatment and placebo arms, using a linear mixed-effect model, adjusted for site effect and within-subject correlation.
Of 54 enrolled subjects, 46 completed the protocol for primary analysis. We observed 6 treatment-emergent AEs grade ≥ 3 (4 treatment-related). All subject in Arm 1 achieved HIV VL < 50 c/ml after resuming ART. The median baseline cell-associated p24 was 22.88 fg/106 CD4+ T cells for Arm 1, 12.47 for Arm 2 and 34.12 for Arm 3. At week 20, the median p24 was 0.56 for Arm 1, 7.95 for Arm 2 and 57.69 for Arm 3. Compared to Arm 3 (ART only control), that had a significant increase in p24 from baseline to week 20 (118%, p < 0.05), we detected a significant decrease in both treatment arm 1 (-73%) and arm 2 (-61%).
Consistent with pilot trial results, a 20-week course of pIFNα-2b resulted in a significant decrease in levels of CD4 T cell-associated inducible HIV compared to ART alone. This effect was independent of ART interruption. This randomized study provides a strong rationale for the use of IFNα immunotherapy as a component of cure-directed strategies.