Pharmacogeneric study of HIV+ patients receiving antiretroviral therapy. We wish to correlate drug concentration with host genetic patients receiving certain HIV drugs. No dosage modification will be carried out and choice of antiretroviral and their dosing will not be influenced by participation in this study.
Conditions
Interventions
Trade Name: Protease inhibitors
Product Name: Protease inhibitor
Pharmaceutical Form: Capsule*
INN or Proposed INN: SAQUINAVIR
CAS Numbe
Sponsors
University of Liverpool
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: age > 18 years known HIV-seropositive either starting or switching antiretroviral regimen (with viral load and CD4 count at 24 weeks), or receiving antiretroviral therapy >2 weeks, and having drug concentration measured. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion age < 18 years not receiving anti-retroviral therapy Written informed consent will be required for all subjects enrolled and a separate section will be utilised to request additional consent to store DNA for future studies, in line with published guidelines [27]. Each subject will be assigned a unique identification code which will be anonymously linked to the following clinical data to be collected: • all subjects: age, gender, ethnic group, clinical stage of disease, pre-existing liver impairment, development of any drug toxicity, development of any clinical event, record of all medications (including doses prescribed), plus • STUDY A change in CD4 count & viral load at 24 weeks, previous ART exposure • STUDY B CD4 count, viral load, reason for requesting TDM, Genomic DNA will be purified and quantified from stored samples by standard phenol-chloroform extraction methods. It is envisaged that a single sample (originating from ~10mL of blood) will yield sufficient ( ? 100?g) quantities of DNA for analysis and storage. Genetic polymorphisms will be defined by PCR-RFLP, sequence-specific PCR, or SNaPshot as optimised for each allele to be examined.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: ; Main Objective: To investigate the association between genetic polymorphisms and a) treatment response (viral load and CD4 count), or b) drug exposure in HIV-positive patients. A candidate gene approach will be utilised to examine the following loci of interest: • Drug metabolism: CYP P450- 2C9, 2D6 and 2C19 • Drug transporters: MDR1 (P-gp), MRP-1, MRP-2, MRP-5 • Protein binding: ORM1 Other candidate genes will emerge as genetic polymorphisms are characterised – these include other drug transporter and metabolising enzymes, and their effect on drug efficacy as well as drug toxicity. ;Primary end point(s): Primary endpoint is defined as change in CD4 count and viral load at 24 weeks, with secondary endpoints of viral load at 12 weeks and time to / proportion achieving undetectable viral load. Patients participating in other studies will not be precluded from this study, and trials measuring plasma drug concentrations at predefined time points will yield especially useful data. | — |
Countries
United Kingdom
Outcome results
None listed