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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

Information source: Catholic University of the Sacred Heart
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Human Immunodeficiency Virus

Intervention: Atazanavir, ritonavir, lamivudine (Drug)

Phase: Phase 4

Status: Active, not recruiting

Sponsored by: Catholic University of the Sacred Heart

Official(s) and/or principal investigator(s):
Mauro MM Moroni, MD, Study Chair, Affiliation: Università di Milano Direttore clinica Malattie infettive
Pierluigi PZ Zoccolotti, MD, Study Chair, Affiliation: Università di Roma La Sapienza Dipartimento di Psicologia
Stafano SV Vella, MD, Study Chair, Affiliation: Dipartimento del farmaco all'Istituto Superiore della Sanità
Roberto RC Cauda, MD, Principal Investigator, Affiliation: Università Cattolica del S. Cuore Policlinico Universitario A. Gemelli

Summary

The purpose of this study is to evaluate the virological efficacy of maintenance therapy with atazanavir with ritonavir combined with lamivudine in treatment experienced HIV positive patients with full and stable virological suppression.

Clinical Details

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 design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Proportion of patients with viral load < 50 copies/mL

Secondary outcome: Efficacy and the safety of atazanavir with ritonavir combined with lamivudine in treatment experienced HIV positive patients with full and stable virological suppression

Detailed description: The introduction of combined antiretroviral therapy (cART) dramatically improved the prognosis of HIV infection [1]; 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.

Eligibility

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria

- HIV positive patients 18 years of age or older who signed an informed consent form

- Already on cART, without any treatment interruption.

- Treated with a cART regimen containing atazanavir boosted with ritonavir since at

least 3 months

- With full virological suppression (VL<50 copies/mL) for a minimum of six months and

in at least in two consecutive determination 3 months +/-2 weeks apart from each other

- With CD4 cell count >200 since at least 6 months and without opportunistic infections

or other AIDS-related events since at least one year before screening Exclusion Criteria:

- Previous virological failure on a lamivudine- or PI-containing regimen or previous

exposure to lamivudine-containing suboptimal antiretroviral regimens

- Patients with at least a single viral load blip over 200 copies/mL

- Patients with M184V or major atazanavir resistance mutation at previous genotypic

resistance test (historical genotype)

- Pregnancy or lactation, planned pregnancy in the short-term

- Patients with HBsAg positive chronic HBV infection

- Patients who experienced major toxicities related to any of the study drugs in the

past

- Patients with grade 4 laboratory abnormalities at baseline (excluding lipid profile

and plasma bilirubin concentration).

- Patients with non-AIDS related illnesses which could, in the Clinician's judgement,

jeopardize the patient's compliance to the study procedures (i. e. Child-Pugh B or higher liver cirrhosis, active cancers on treatment…).

- Patients treated with proton-pump inhibitors or other concomitant medication with

potential for interactions reducing exposure to atazanavir

Locations and Contacts

Azienda Ospedaliero Universitaria - Ospedali Riuniti di Ancona Struttura Organizzativa Dipartimentale (S.O.D) Clinica di Malattie infettive, Ancona 60126, Italy

Azienda Ospedaliera Spedali Civili - Istituto di Malattie Infettive e Tropicali, Brescia 25123, Italy

Azienda Ospedaliera di Rilievo Nazionale di alta specializzazione Garibaldi di Catania - Istituto Malattie infettive, Catania 95122, Italy

Azienda Ospedaliera Universitaria San Martino - Clinica Malattie Infettive, Genova 16132, Italy

A.O. Ospedale Niguarda Cà Granda - Malattie Infettive, Milano 20126, Italy

Ospedale Luigi Sacco di Milano - Malattie infettive I Divisione, Milano 20157, Italy

Ospedale Luigi Sacco di Milano Azienda ospedaliera e Polo Universitario - Dip. di Scienze Cliniche L. Sacco / Sez. Malattie Infettive, Milano 20157, Italy

Ospedale San Raffaele, Milano 20127, Italy

A.O. Universitaria Policlinico Paolo Giaccone di Palermo - Malattie Infettive, Palermo 9127, Italy

Ospedale S. Maria della Misericordia, Perugia 06129, Italy

I.N.M.I. L. Spallanzani I.R.C.C.S. - .O.C. Malattie Infettive e Tropicali IV Divisione, Roma 00149, Italy

I.N.M.I. L. Spallanzani I.R.C.C.S. - U.O.C. Infezioni Sistemiche e dell'Immunodepresso II Divisione, Roma 00149, Italy

IRCCS Istituto Dermatologico S. Gallicano (IFO) - UOC Dermatologia Infettiva, Roma 00144, Italy

Università Cattolica del S. Cuore Policlinico Universitario A. Gemelli - Istituto di Clinica delle Malattie Infettive, Roma 00168, Italy

Università' degli studi di Roma La Sapienza - Dipartimento di Malattie Infettive e Tropicali, Roma 00161, Italy

Università degli studi di Sassari - Reparto Malattie Infettive, Sassari 07100, Italy

Ospedale Amedeo di Savoia - Divisione A Malattie Infettive, Torino 10149, Italy

Azienda ULSS 9 Treviso Ospedale S. Maria di Ca'Foncello - U.O. Malattie infettive, Treviso 31100, Italy

Azienda Ospedaliera Universitaria Integrata di Verona - U.O.C. Malattie infettive, Verona 37134, Italy

Ospedale S. M. Annunziata - U.O. Malattie Infettive, Bagno a Ripoli, Firenze 50011, Italy

P.O. "S. Caterina Novella" - UOC di Malattie Infettive, Galatina, Lecce 73013, Italy

Additional Information

Starting date: July 2011
Last updated: July 31, 2014

Page last updated: August 23, 2015

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