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Pharmacokinetics, safety and efficacy of atazanavir /dolutegravir/lamivudine regimen as maintenance regimen in patients with intolerance and/or resistance to NRTIs, NNRTIs and RTV: a pilot study (PRADA II study)

Phase 2
Completed
Conditions
HIV
human immunodeficiency virus
10047438
Registration Number
NL-OMON42090
Lead Sponsor
niversitair Medisch Centrum Sint Radboud
Brief Summary

Trial is onging in other countries

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
Not specified
Target Recruitment
9
Inclusion Criteria

1. HIV-infected as documented by positive HIV antibody test and confirmed by Western Blot.
2. Subject is in need for a switch in maintenance regimen due to adverse effects, toxicities, simplification and/or resistance.
3. Subject is at least 18 years of age at the day of screening.
4. Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
5. HIV-1 RNA < 40 copies/mL for at least 6 months on antiretroviral therapy prior to inclusion.
6. Subject has no documented resistance mutations to PIs, INSTIs or lamivudine.

Exclusion Criteria

1. Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
2. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
3. Inability to understand the nature and extent of the trial and the procedures required.
4. Pregnant female (as confirmed by an HCG test performed less than 3 weeks before the first dose) or breast-feeding female.
5. Abnormal serum transaminases determined as levels being > 5 times upper limit of normal (see Appendix A for normal ranges of clinical laboratory values).
6. Renal failure determined as an estimated Glomerular Filtration Rate (eGFR) < 50 ml/min (MDRD-based).
7. Concomitant use of medications that interfere with atazanavir, dolutegravir or lamivudine pharmacokinetics: oxcarbamazepine, phenytoin, phenobarbital, carbamazepine, St. John*s wort, rifampicin, clarithromycin, H2 receptor antagonists, proton pump inhibitors, irinotecan, midazolam, triazolam, buprenorfine, aprepitant, modafinil, imatinib, co-trimoxazole, other antiretroviral drugs.
8. Concomitant use of medications that are contraindicated for use with atazanavir, dolutegravir or lamivudine: alfuzosin, pimozide, quetiapine, kinidine, bepridil, simvastatin, atorvastatin, lovastatin, sildenafil (as for use in pulmonary arterial hypertension), cladribine.
9. Active hepatobiliary or hepatic disease (including chronic hepatitis B or C infection).
10. Alcohol abuse.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<p>Pharmacokinetic parameters (AUC0-24h, Cmax, Ct, C24h, Tmax, T1/2) for<br /><br>atazanavir, dolutegravir en lamivudine. Values will be compared to historical<br /><br>data. </p><br>
Secondary Outcome Measures
NameTimeMethod
<p>HIV viral load and CD4 count (efficacy) and adverse events (safety). </p><br>
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