pharmacokinetics of atazanavir /dolutegravir/lamivudine regimen as maintenance regimen

Conditions: HIV-1 Infection

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.


Eligibility criteria:
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.