Clinical trial NCT00999739: Conjugate And Polysaccharide Vaccines Compared With Polysaccharide Vaccine In Hiv-Infected Adults
Official title: A Sequential Vaccination Strategy With Conjugated and Polysaccharide Pneumococcal Vaccines Compared With Polysaccharide Vaccine in HIV- Infected Adults.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Pneumococcal Vaccines
HIV
HIV Infections
Keywords: pneumococcal vaccines
HIV
antibody response
antibody affinity
Antibody formation
Phagocytosis
Lead sponsor: Hospital Universitari Son Dureta
Sponsor class: OTHER
Collaborators: name: Hospital Son Llatzer
name: Fondo de Investigacion Sanitaria
First posted: 2009-10-22
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Randomised study comparing two pneumococcal vaccination strategies in HIV-infected adults with moderate immunossupression (CD4 between 200 and 500 cells/uL and viral load under 5logs), one with conjugated heptavalent vaccine(Prevenar, Wyeth-Lederle) followed by polysaccharide vaccine 4 weeks after (Aventis-Pasteur), and two with one dose of polysaccharide vaccine. Determination of secondary effects related to both vaccines and determination of antibody concentration (ELISA) and avidity (ELISA with thiocyanate) and opsonophagocytosis killing activity against the seven serotypes included in the heptavalent vaccine before vaccination, at 4 weeks, at 8 weeks, at48 weeks and 96 weeks. A sample of 220 HIV-infected adults (110 in each group) will be needed to detect differences of 10% for a type I error o 5% for a limited population of 2500 HIV-infected adults. The main hypothesis are :the immunogenicity of pneumococcal vaccination with conjugate and polysaccharide vaccines is superior to immunogenicity induced by polysaccharide vaccination alone(antibody concentration), the avidity and opsonophagocytosis induced by two vaccines is better than the one after polysaccharide vaccine alone, both vaccinations are safe.

Detailed description: Randomised study comparing two pneumococcal vaccination strategies in HIV-infected adults with moderate immunossupression (CD4 between 200 and 500 cells/uL and viral load under 5logs), one with conjugated heptavalent vaccine(Prevenar, Wyeth-Lederle) followed by polysaccharide vaccine 4 weeks after (Aventis-Pasteur), and two with one dose of polysaccharide vaccine. A sample of 220 HIV-infected adults will be randomised to receive twe strategy one(110 patients) one dose of heptavalent conjugated vaccine at day 0 and one dose of polysaccharide vaccine at week 4 (in deltoid muscle); or strategy two (110 patients) one dose of polysaccharide vaccine at day 0. Secondary effects to the vaccines will be evaluated by phone interview 3 days after vaccinations.

Blood samples will be taken at day 0(before the first vaccine), at week 4 before the polysaccharide in the group one, and 4 weeks after the polysaccharide in the group two) and at week 8 in the group one, and at weeks 48 and 96 in both groups Antibody concentration , avidity, and opsonophagocytic killing activity will be measured in all the samples for serotypes 4,14,19F,23F,6B,18C,9V.

Antibody concentration , avidity, and opsonophagocytic killing activity will be compared between both vaccine groups, and between prevaccination and at 4,8, 48 and 96 weeks of vaccination. Risk factors associated to good antibody response (antibody duplication and antibody duplication plus achieve a level above 1ug/ml)will be measured at 8, 48 and96 weeks.

Eligibility criteria: Inclusion Criteria:

* HIV-infected adults with CD4 between 200 and 500 cels/ul and viral load under 5 logarithm

Exclusion Criteria:

* previous pneumococcal vaccine, pregnancy, advanced renal or liver disease, other vaccine or antibiotics 6 weeks before, other immunosuppression, immunoglobulins or investigation drugs

Primary outcomes:
measure: Antibody response in terms of antibody concentration at 4,8,48 and 69 weeks of vaccination
timeFrame: 4, 8, 48 and 96 weeks of vaccination
Secondary outcomes:
measure: Avidity of the antibodies induced in the two vaccination groups before and at 4 ,8 , 48 and 96 weeks of vaccination
timeFrame: 4 , 8 ,48 and 96 weeks after vaccintation
measure: safety of both vaccines
timeFrame: 3 days
measure: risk factors associated to a good vaccine response
timeFrame: 8 weeks, 48 weeks, 96 weeks
measure: opsonophagocytic activity against the seven polysaccharides before, and after 4,8,48 and 96 weeks of vaccination
timeFrame: 4,8,48 and 96 weeks
Other outcomes:
Locations:
city: Palma de Mallorca
country: Spain
facility: Hospital Son Dureta
state: Illes Balears
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
state: Illes Balears
Study officials:
affiliation: Hospital Son Dureta
name: maria penaranda, physician
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Son Llatzer
name: antonio payeras, physician
role: PRINCIPAL_INVESTIGATOR
References:
citation: Penaranda M, Payeras A, Cambra A, Mila J, Riera M; Majorcan Pneumococcal Study Group. Conjugate and polysaccharide pneumococcal vaccines do not improve initial response of the polysaccharide vaccine in HIV-infected adults. AIDS. 2010 May 15;24(8):1226-8. doi: 10.1097/QAD.0b013e3283389de5.