Atazanavir/r + Lamivudine Dual Therapy (ATLAS)
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|ClinicalTrials.gov Identifier: NCT01599364|
Recruitment Status : Completed
First Posted : May 16, 2012
Last Update Posted : July 24, 2019
|Condition or disease||Intervention/treatment||Phase|
|Human Immunodeficiency Virus||Drug: Atazanavir, ritonavir, lamivudine||Phase 4|
The introduction of combined antiretroviral therapy (cART) dramatically improved the prognosis of HIV infection ; nowadays, virological suppression (viral load < 50 copies/mL) can be obtained in the vast majority of patients receiving cART. Nevertheless, antiretroviral drugs have short- and long-term side effects mainly regarding mitochondrial toxicity, impaired lipid and glucose metabolism, impairment of renal function and bone density and may contribute to increase the patients' cardiovascular risk.
Current treatment guidelines recommend three drug regimens with a "backbone" of 2 nucleos(t)ide reverse transcriptase inhibitors (N(t)RTIs) and a "third drug" to be chosen among non-nucleoside reverse transcriptase inhibitors (NNRTIs) and ritonavir-boosted protease inhibitors (PIr). Regimens containing less than three antiretroviral drugs are currently not recommended based on the high risk of virological failure and selection of drug resistance mutations (DRM) with previous experience of NRTI-only based approaches with the exception of boosted PIs monotherapy which is optional in patients with intolerance to NRTIs or requiring treatment simplification provided that they never experienced virological failures or admitted in exceptional circumstances.
Nevertheless, the investigation of possible new treatment paradigms remains attractive due to the high potency and low risk of selection of drug resistance mutations with PIr based therapies and the established long term toxicity of even newer and currently preferred N(t)RTIs, in particular the renal and bone toxicity of tenofovir and the debated potential association with increased cardiovascular risk of abacavir, which has been described in some cohort studies. Studies evaluating N(t)RTI-sparing treatment strategies are thus increasing in order to try to respond to the unmet medical needs of HIV-infected patients with metabolic complications and increasing risk of cardiovascular or renal diseases.
These studies will need to investigate the safety and efficacy of these alternative strategies, also evaluating their possible effects on renal function, bone mass density and risk of premature osteoporosis.
Atazanavir with ritonavir is a generally well tolerated lipid-friendly protease inhibitor with mild effects on lipid metabolism even when combined with low-dose ritonavir and is the only drug who achieved a non-significant difference in virological efficacy compared to efavirenz; like all other PIr-based regimens, failure of an atazanavir/ritonavir containing cART seems to protect against the development of drug resistance mutations to both the PI and the backbone. Lamivudine is a well tolerated NRTI which showed no significant toxicity in the short and long term and, together with its analog emtricitabine, is now a preferred option in most of the major international treatment guidelines; it has a good CNS penetration score and its only signature resistance mutation (M184V) deeply impairs the viral fitness and does not compromise the future treatment options.
The combination of these two drugs could therefore be an appealing possibility for treatment switch in stably virologically suppressed treatment-experienced patients with toxicity-related issues. The results of a previously planned 24 weeks interim analysis of a monocentric 48 weeks Italian pilot study evaluating this strategy in 40 patients has recently been presented at IAS conference in Vienna and showed no virologic failures without any "blip" and good tolerability with a significant improvement of renal function as measured by MDRD. These data look very promising and allow us to be confident in designing a randomized study in order to confirm these findings.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||266 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Safety and Efficacy of Switching a Stable Combined Antiretroviral Therapeutic Regimen to Atazanavir With Ritonavir Plus Lamivudine in Treatment Experienced HIV Positive Patients With Full and Stable Virological Suppression|
|Study Start Date :||April 2014|
|Actual Primary Completion Date :||April 2016|
|Actual Study Completion Date :||February 23, 2018|
Switch to Atazanavir 300 mg with ritonavir 100 mg plus lamivudine 300 mg
Drug: Atazanavir, ritonavir, lamivudine
Lamivudine 300 mg 1 pill once-a-day, atazanavir 300 mg 1 pill with ritonavir 100 mg 1 pill once-a-day, taken together orally with a light meal
Other Name: Lamivudine (Epivir, GSK), Atazanavir (Reyataz, BMS), Ritonavir (Norvir, Abbott)
No Intervention: continue
Continue Atazanavir 300 mg with ritonavir 100 mg with the same NRTI backbone
- Proportion of patients with viral load < 50 copies/mL [ Time Frame: at week 48 ]Proportion of patients with viral load < 50 copies/mL at week 48 at the intention-to-treat with switch = failure analysis
- Efficacy and the safety of atazanavir with ritonavir combined with lamivudine in treatment experienced HIV positive patients with full and stable virological suppression [ Time Frame: 48 and 96 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01599364
|Study Chair:||Mauro MM Moroni, MD||Università di Milano Direttore clinica Malattie infettive|
|Study Chair:||Pierluigi PZ Zoccolotti, MD||Università di Roma La Sapienza Dipartimento di Psicologia|
|Study Chair:||Stafano SV Vella, MD||Dipartimento del farmaco all'Istituto Superiore della Sanità|
|Principal Investigator:||Roberto RC Cauda, MD||Università Cattolica del S. Cuore Policlinico Universitario A. Gemelli|