HIV-1 Infection
Conditions
Brief summary
During the past years the treatment of HIV-1 infection has transformed towards chronic treatment. Patients are being treated with antiretroviral drugs for many years and become older. The risk of developing side-effects due to long term antiretroviral therapy is therefore more and more likely. New alternative once-daily maintenance regimes are needed for those who are extensively pre-treated and experience side-effects or toxicity on standard treatment combinations. A possible once-daily, fully active maintenance regimen is the combination of atazanavir (unboosted), dolutegravir and lamivudine (PRADAII regimen). This combination is expected to be a safe, once-daily maintenance regimen with a favorable side-effect profile. The combination suits patients with intolerance and/or resistance to NRTIs, NNRTIs and ritonavir, who have a suppressed viral load. However, for this new combination the pharmacokinetic profile is unknown and there are no data on short-term and long-term safety and efficacy. This study wille therefore asses the pharmacokinetics, safety and efficacy in a small number of HIV-1 infected patients.
Interventions
DRUGAtazanavir
HIV therapy will be adapted: atazanavir 400mg QD
DRUGDolutegravir
HIV therapy will be adapted: dolutegravir 50mg QD
DRUGLamivudine
HIV therapy will be adapted: lamivudine 300mg QD
Sponsors
Radboud University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV-infected as documented by positive HIV antibody test and confirmed by Western Blot. * Subject is in need for a switch in maintenance regimen due to adverse effects, toxicities, simplification and/or resistance. * Subject is at least 18 years of age at the day of screening. * Subject is able and willing to sign the Informed Consent Form prior to screening evaluations. * HIV-1 RNA \< 40 copies/mL for at least 6 months on antiretroviral therapy prior to inclusion. * Subject has no documented resistance mutations to PIs, INSTIs or lamivudine.
Exclusion criteria
* Documented history of sensitivity/idiosyncrasy to medicinal products or excipients. * Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion. * Inability to understand the nature and extent of the trial and the procedures required. * Pregnant female (as confirmed by an HCG test performed less than 3 weeks before the first dose) or breast-feeding female. * Abnormal serum transaminases determined as levels being \> 5 times upper limit of normal. * Renal failure determined as an estimated Glomerular Filtration Rate (eGFR) \< 50 ml/min (MDRD-based). * Concomitant use of medications that interfere with atazanavir, dolutegravir or lamivudine pharmacokinetics: oxcarbazepine, phenytoin, phenobarbital, carbamazepine, St. John's wort, rifampicin, clarithromycin, H2 receptor antagonists, proton pump inhibitors, irinotecan, midazolam, triazolam, buprenorphine, aprepitant, modafinil, imatinib, co-trimoxazole, other antiretroviral drugs. * Concomitant use of medications that are contraindicated for use with atazanavir, dolutegravir or lamivudine: alfuzosin, dofetilide, pimozide, quetiapine, quinidine, bepridil, simvastatin, atorvastatin, lovastatin, sildenafil (as for use in pulmonary arterial hypertension), cladribine. * Active hepatobiliary or hepatic disease (including chronic hepatitis B or C infection). * Alcohol abuse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the plasma concentration versus time curve (AUC) of atazanavir, dolutegravir and lamivudine | week 2 | Pharmacokinetic parameters of atazanavir, dolutegravir and lamivudine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| efficacy (viral load) | week 2, 6 and 12 | efficacy (viral load) of the combination of atazanavir, dolutegravir and lamivudine |
| number of adverse events | week 2, 6 and 12 | number of adverse events of the combination of atazanavir, dolutegravir and lamivudine |
Countries
Germany, Netherlands
Outcome results
None listed