HIV Infections
Conditions
Keywords
HIV Infection, Dendritic cell vaccine, Autologous virus, Heat inactivated, HIV Therapeutic Vaccine
Brief summary
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.
Detailed 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.
Interventions
BIOLOGICALDendritic cell vaccine
107 DC subcutaneous 3 doses every 2 weeks
BIOLOGICALnon pulsed dendritic cell untreated patients
107 DC subcutaneous 3 doses every 2 weeks
BIOLOGICALpulsed dendritic cell vaccine
107 DC subcutaneous 3 doses every 2 weeks
BIOLOGICALdendritic cell vaccine
107 DC subcutaneous 3 doses every 2 weeks
BIOLOGICALnon pulsed dendritic cell vaccine
107 DC subcutaneous 3 doses every 2 weeks
Sponsors
Hospital Clinic of Barcelona
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Comparison of steady state viremia (so-called viral set point) after 6-12 months after vaccination with viremia before HAART. | 6 and 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Proportion with evidence of HIV-specific T-cell proliferative response comparing end of immune-based therapy, and end of trial (week 48) with start of immune-based therapy. | 6 and 12 months |
| Proportion with evidence of HIV-specific neutralizing activity of serum comparing end of immune-based therapy, and end of trial (week 48) with start of immune-based therapy. | 6 and 12 months |
| Proportion with evidence of HIV-specific CTL comparing end of immune-based therapy, and end of trial (week 48) with start of immune-based therapy. | 6 and 12 months |
| DC Migration | 0 and 2 weeks |
| Viral load in semen and vaginal secretions | 0 and 6 months |
| HIV-1 specific CTL responses in lymphoid tissue | 0 and 6 months |
Countries
Spain
Outcome results
None listed