Pharmacokinetics of Atazanavir /Dolutegravir/Lamivudine Regimen as Maintenance Regimen (PRADAII)

Radboud University Medical Center

Status and phase

Terminated

Phase 2

Conditions

HIV-1 Infection

Treatments

Drug: Atazanavir

Drug: Dolutegravir

Drug: Lamivudine

Study type

Interventional

Funder types

Other

Identifiers

NCT02566707

UMCN-AKF 14.08

Details and patient eligibility

About

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.

Enrollment

9 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.