A double-blind placebo-controlled randomized therapeutic vaccine trial with myeloid derived-dendritic cells (MD-DC) loaded with heat-inactivated autologous HIV-1 (HIAH) plus pegylated Interferon-alpha (pIFN) in HIV-1 chronic infected patients on antiretroviral treatment (ART) to achieve functional cure was performed.
36 patients on successful ART with CD4+ ≥450 cells/mm3 were randomized 1:1:1:1 and 29 received at w0, 2 and 4 an ultrasound-guided inguinal intranodal dose of: 1) vaccine (V) 107 MD-DC pulsed with 1010 HIAH (n=8); 2) V plus 3 doses of pIFN (VpIFN) at w4, 5 and 6 (n=6); 3) placebo (P) (n=7); and 4) P plus 3 doses of pIFN (PpIFN) at w4, 5 and 6 (n=8). ART was interrupted (ATI) at week 4. The primary end-points were safety and proportion of patients with undetectable VL 12w after ATI (w16). Secondary end-points were DVL set-point (set-point ATI-preART), and DHIV-1 specific T cell responses (IFN-ƴ Elispot) (w16-w0).
All participants were male. The procedure was safe and well tolerated. All patients had detectable VL at w16. DVL set-point [log10 mean (SE) copies/ml) was: 1) V 0,20 (0,21) 2) VpIFN -0.44 (0,38) 3) P -0,19 (0,23) 4) PpIFN -0,17 (0,20) (p=0.37). A decrease >1log10 in VL set-point was seen in 0, 3, 1 and 0 patients in V, VpIFN, P and PpIFN, respectively (p=0.05 and p= 0.06 for the differences between VpIFN vs V, and VpIFN vs PpIFN, respectively). At baseline, HIV-1 specific T-cell responses were lower in vaccines vs placebo groups [mean (SE) 900 (200) vs 2259 (535) SFC/106 PBMC, p=0.028). No significant differences in DHIV-1 specific T-cell responses were observed between vaccine and placebo groups (p=0.09). No effect on T cell responses was observed with pIFN administration. A trend to significative negative correlation between DVL and DHIV-specific T-cell responses (w16-w0) was observed in vaccine and not in placebo groups (r=-0.56, p=0.09; r-028, p= 0.43; vaccine and placebo groups, respectively).
The combination of a MD-DC therapeutic vaccine and pegIFNα was safe. A very modest decrease in VL was observed in vaccine recipients and was correlated with an increase of HIV-1 specific T-cell responses.
Clinical trial.gov EudraCT 2015-001795-22