Dendritic Cell Vaccine in HIV-1 Infection

Hospital Clinic of Barcelona

Status and phase: Completed; Phase 2; Phase 1

Conditions: HIV Infections

Treatments: Biological: Dendritic cell vaccine; Biological: dendritic cell vaccine; Biological: non pulsed dendritic cell vaccine; Biological: pulsed dendritic cell vaccine; Biological: non pulsed dendritic cell untreated patients

Study type: Interventional

Funder types: Other

Identifiers

NCT00402142

DCV-02/MANON07

Details and patient eligibility

About

1. To study the efficacy of a therapeutic HIV vaccine consisting of autologous myeloid dendritic cells pulsed ex vivo with high doses of inactivated autologous HIV-1, in HIV-1 infected patients in a very early stages of the disease (CD4 > 450 x 10 6 /L).
2. To analyze the HIV-1 humoral and cellular immune responses induced by this immune-based therapy.

Full description

Our group has reported recently the first human trial of 4 therapeutic immunizations at six-week intervals with autologous monocyte-derived dendritic cells (MD-DC) loaded with heat-inactivated autologous HIV in 12 HIV infected patients who had been receiving highly active antiretroviral therapy (HAART) since early chronic infection. Autologous HIV was concentrated from plasma (1,500 ml) obtained by plasmapheresis after a 3-month HAART interruption (STOP1) performed 78 weeks before therapeutic immunizations, and HAART was discontinued again (STOP2) after therapeutic immunization. There was a decrease of set-point plasma viral load (PVL) >= 0.5 log after 24 weeks off HAART in 4 out of 12 patients. In addition, we observed a significant lengthening in mean doubling time of PVL rebound (p= 0.01), and significant decreases in the area under the curve of PVL rebound (p= 0.02) and in the mean peak PVL (p= 0.004) during the 12 weeks after STOP 2 compared with STOP1. This virological response was associated with a weak but significant increase in HIV-1 specific CD4 lymphoproliferative response, and with changes in HIV-1 specific CD8+ T-cell responses in peripheral blood and in lymphoid CTL cells after immunization. In lymphoid tissue, we also observed a trend towards a better control of HIV-1 replication coupled with an increase of CD4+ and CTL cells. No significant virological or immunological changes occurred in controls. We show that a therapeutic vaccine with autologous MD-DC pulsed with heat inactivated autologous HIV-1 is feasible, safe and well tolerated and elicited weak and transient cellular immune responses against HIV, associated with a partial and transient control of HIV replication in some patients.

we hypothesized that a DC vaccine pulsed with higher amount of autologous virus obtained by culture could be more effective than the vaccine we used.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Confirmed HIV infection
• CD4 > 450 x 10 6 /L
• baseline VL >10,000 c/ml before any HAART
• Part I, patients off HAART at least during 6 months
• Part II, Patients on HAART with PVL < 200 copies/ml at least during 6 months
• Written informed consent .

Exclusion criteria

• Patients with failure to HAART
• Patients with B or C symptoms (CDC classification 1993).
• Age < 18 years old.
• Pregnant or breastfeeding women
• Patients with baseline creatinin > 2.5 mg/dl
• Patients with baseline GOT/GPT > 250 UI/L

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

60 participants in 5 patient groups, including a placebo group

Pulsed dendritic cells untreated patients

Active Comparator group

Description:

Untreated patients receiving a dendritic cell based vaccine pulsed with autologous heat iactivated virus

Treatment:

Biological: Dendritic cell vaccine

non pulsed dendritic cells untreated patients

Placebo Comparator group

Treatment:

Biological: non pulsed dendritic cell untreated patients

pulsed dendritic cell treated patient

Active Comparator group

Description:

treated patients will be immunized with a dendritic cell vaccine pulsed with heat inactivated autologous virus immediately before art interruption

Treatment:

Biological: pulsed dendritic cell vaccine

pulsed dendritic cell in treated patients

Active Comparator group

Description:

patients will be immunized with a dendritic cell vaccine pulsed with heat inactivted autologous virus immediately after interruption of art

Treatment:

Biological: dendritic cell vaccine

non pulsed dendritic cells

Placebo Comparator group

Treatment:

Biological: non pulsed dendritic cell vaccine