Progress Towards A Therapeutic HIV Vaccine
Current management of chronic HIV infection is "cART for life". In order to achieve a functional HIV cure, therapeutic vaccination could be an interesting way if it is capable of controlling viral replication without drugs.
A new step is reported by a spanish group (1) using using autologous myeloid dendritic cells (MD-DCs) pulsed with autologous heat-inactivated whole HIV.
Although this blinded placebo-controlles trial did not prevent viremia rebound after cART discontinuation, it showed a significant reduction in viremia levels in the vaccine arm.
The protocol included 36 patients, 24 in the DC-HIV group and 11 in the control group with placebo.
cART was stopped a first time at W-56 and autologous virus was collected at W-52.
cART was then reintroduced at W-48 and stopped again at W0 following 3 administrations of the vaccine (with at least 107 MD-DCs pulsed with heat-inactivated autologous virus, 109 copies per dose).
Overall, the immunizations were well tolerated with mainly enlargement of local lymph nodes, local redness and flu-like symptoms.
DC-HIV patients experienced significant changes of plasma viral load (pVL) setpoint after cART interruption compared to DC controls.
At weeks 12 and 24, a decrease of pVL setpoint of >1 log was observed in 12 of 22 (55%) verus 1 of 11 (9%) individuals, and in 7 of 20 (35%) verus 0 of 10 (0%) individuals in DC-HIV and DC controls, respectively (p=0.02 and p=0.03).
Despite these reductions, VL rebounded to detectable levels in all patients.
CD4 T cell counts declined to pre-c-ART values without significant differences between groups.
A significant median change in lymphoproliferative response to HIV p24 was found at W 24 in the DC-HIV group.
These patients were chronically infected at non advanced stages of disease.
The significant and consistent virologic response was maintained for at least 24 weeks in the vaccinated group and seemed to wane thereafter. Over this 48 week period, the AUC analysis showed a significant difference for a change of pVL setpoint between the groups with a mean drop of -0.73 in vaccinated versus -0.24 in controls.
Although these data fell short of achieving a functional cure, they are a proof of concept that a therapeutic vaccine was capable of changing pVL setpoint after a diagnostic interruption of cART.
Garcia F, Climent N, Guardo AC et al. A Dendritic Cell-Based Vaccine Elicits T Cell Responses Associated with Control of HIV-1 Replication.Sci. Transl. Med. 5, 166ra2 (2013)
Key words: HIV cure, HIV reservoirs, HIV vaccine