Atazanavir/r + Lamivudine Dual Therapy
- Conditions
- Human Immunodeficiency Virus
- Interventions
- Drug: Atazanavir, ritonavir, lamivudine
- Registration Number
- NCT01599364
- Lead Sponsor
- Catholic University of the Sacred Heart
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 266
Not provided
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Switch Atazanavir, ritonavir, lamivudine Switch to Atazanavir 300 mg with ritonavir 100 mg plus lamivudine 300 mg
- Primary Outcome Measures
Name Time Method Proportion of patients with viral load < 50 copies/mL at week 48 Proportion of patients with viral load \< 50 copies/mL at week 48 at the intention-to-treat with switch = failure analysis
- Secondary Outcome Measures
Name Time Method Efficacy and the safety of atazanavir with ritonavir combined with lamivudine in treatment experienced HIV positive patients with full and stable virological suppression 48 and 96 weeks
Trial Locations
- Locations (21)
P.O. "S. Caterina Novella" - UOC di Malattie Infettive
🇮🇹Galatina, Lecce, Italy
Azienda Ospedaliero Universitaria - Ospedali Riuniti di Ancona Struttura Organizzativa Dipartimentale (S.O.D) Clinica di Malattie infettive
🇮🇹Ancona, Italy
Azienda Ospedaliera Spedali Civili - Istituto di Malattie Infettive e Tropicali
🇮🇹Brescia, Italy
Azienda Ospedaliera di Rilievo Nazionale di alta specializzazione Garibaldi di Catania - Istituto Malattie infettive
🇮🇹Catania, Italy
Ospedale S. M. Annunziata - U.O. Malattie Infettive
🇮🇹Bagno a Ripoli, Firenze, Italy
Azienda Ospedaliera Universitaria San Martino - Clinica Malattie Infettive
🇮🇹Genova, Italy
Ospedale San Raffaele
🇮🇹Milano, Italy
Ospedale Luigi Sacco di Milano Azienda ospedaliera e Polo Universitario - Dip. di Scienze Cliniche L. Sacco / Sez. Malattie Infettive
🇮🇹Milano, Italy
I.N.M.I. L. Spallanzani I.R.C.C.S. - .O.C. Malattie Infettive e Tropicali IV Divisione
🇮🇹Roma, Italy
IRCCS Istituto Dermatologico S. Gallicano (IFO) - UOC Dermatologia Infettiva
🇮🇹Roma, Italy
Ospedale S. Maria della Misericordia
🇮🇹Perugia, Italy
I.N.M.I. L. Spallanzani I.R.C.C.S. - U.O.C. Infezioni Sistemiche e dell'Immunodepresso II Divisione
🇮🇹Roma, Italy
Università ' degli studi di Roma La Sapienza - Dipartimento di Malattie Infettive e Tropicali
🇮🇹Roma, Italy
Università Cattolica del S. Cuore Policlinico Universitario A. Gemelli - Istituto di Clinica delle Malattie Infettive
🇮🇹Roma, Italy
Ospedale Amedeo di Savoia - Divisione A Malattie Infettive
🇮🇹Torino, Italy
Università degli studi di Sassari - Reparto Malattie Infettive
🇮🇹Sassari, Italy
Azienda ULSS 9 Treviso Ospedale S. Maria di Ca'Foncello - U.O. Malattie infettive
🇮🇹Treviso, Italy
Azienda Ospedaliera Universitaria Integrata di Verona - U.O.C. Malattie infettive
🇮🇹Verona, Italy
A.O. Ospedale Niguarda CÃ Granda - Malattie Infettive
🇮🇹Milano, Italy
Ospedale Luigi Sacco di Milano - Malattie infettive I Divisione
🇮🇹Milano, Italy
A.O. Universitaria Policlinico Paolo Giaccone di Palermo - Malattie Infettive
🇮🇹Palermo, Italy