Recent HIV-1 Infection
Conditions
Brief summary
Study to evaluate the safety, tolerability and antiretroviral activity of a new therapeutic strategy, based on the administration of dasatinib, an ITK, in patients with recent (3-12 months) asymptomatic HIV-1 infection.
Interventions
DRUGDasatinib
Dasatinib monotherapy 70 mg/day, during 16 weeks.
DRUGPlacebo
Placebo during 16 weeks.
Sponsors
Eva Bonfill
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 18 to 65 years. * Documented asymptomatic HIV-1 infection of more than 3 months' duration (all patients must have a positive Western blot, including the p31 band whose appearance indicates infection of more than 90 days duration). * Not having received ART * CD4 T-lymphocyte count\> 350 / μl * Patient giving written informed consent
Exclusion criteria
* Active HBV (HBsAg+ or DNA+) and/or HCV (RNA+) infection in screening. * ALT\> 2 UNL, glomerular filtration rate \<70 mL / 1.73 m2, leukocytes \<4000 / mm3, total lymphocyte count \<1000 / mm3, platelets \<100,000 / mm3 or Hg \<12g / dL. * Pregnancy or active breastfeeding * Ongoing or previous pleural effusion * Chronic obstructive pulmonary disease, bronchial asthma or recent chest trauma. * History of gastrointestinal or other bleeding. * Any concomitant treatment with potentially dangerous drug interaction with dasatinib. * Any clinical condition, at the opinion of the investigator, contraindicating participation (for example, * Active neoplastic disease, active concomitant infection, etc.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerance of dasatinib with and without antiretroviral therapy, measured by number of AEs and SAEs | 52 weeks | Measured by number of AEs and SAEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antiretroviral capacity of dasatinib | at week 0 and 4 | Measured by quantification of plasma HIV-1 viral load during 4-week administration of dasatinib monotherapy. |
| Changes in the viral reservoirs of patients with recent HIV-1 infection induced by dasatinib administration. | at week 0, 4, 16 and 52 | Measured by changes in the viral reservoirs (integrated DNA, genetically intact virus, residual and induced viral replication and determination of integration sites) |
| Changes in markers of inflammation and immune activation induced by dasatinib administration. | at week 0, 4, 16 and 52 | Measured by changes in ultra-sensitive CRP, IL6, TNF alpha and CD4/CD8, CD25, CD69, CD38, HLA-DR+. |
| Changes in SAMHD1 phosphorylation levels and cytotoxic activity against HIV-1 induced by dasatinib. | at week 0, 4, 16 and 52 | Measured by NK phenotyping and in vitro replication inhibition tests. |
| Pharmacokinetic interactions of coadministration non-boosted integrase inhibitor-based antiretroviral therapy with dasatinib. | at week 1, 2, 3, 4, 8, 12, 16 | Measured by Cmax |
| Impact of dasatinib on markers of senescence | at week 0, 4, 16 and 52 | Measured by expression in PBLs of beta-galactosidase, Bcl-2, Histone H2A, p16 and CD87. |
Countries
Spain
Outcome results
None listed