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DRV/r + RPV QD: Efficacy and Toxicity Reduction

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by Ospedale L. Sacco – Polo Universitario
Elisa Colella, M.D.
Valentina Di Cristo, M.D.
Massimo Galli, M.D.
Information provided by (Responsible Party):
Stefano Rusconi, Ospedale L. Sacco - Polo Universitario Identifier:
First received: February 7, 2013
Last updated: March 29, 2016
Last verified: March 2016

Clinical approach to HIV infection treatment is based on the use of highly active antiretroviral therapies (HAART) and recent national and international guidelines for guiding HIV therapy recommend the use of triple-combination therapy using antiretrovirals with 2 nucleos(t)ide inhibitors [N(n)RTI] as backbone plus a third drug to be chosen among a boosted protease inhibitor (PI/r), a nonnucleoside inhibitor (NNRTI) or an integrase inhibitor (II).

In spite of evident efficacy of HAART, as demonstrated by survival increasing, long term side effects, as for example the impact on renal function, remain principal problem.

In patient with risk factor for renal disease, a reduction of eGRF (estimated Glomerular Filtration Rate) between 90 and 60 mL/min/1,73 m2 could be already considered as a risk condition [1,2].

Efficacy of HAART, with increase of media survival and the parallel decrease of mortality, has underlined the necessity to reflect on long term HAART effects [3].

There are many evidences of HAART-related toxicity that, in spite of the necessity of a life-saving therapy, focus on the additional costs of this situation, in terms of health as well as in terms of economic costs.

Particular attention has been focused on the impact of some drugs on renal function, as tenofovir, especially on tubule, without forgetting the modification of lipid and bone metabolisms.

According to further studies which have evidenced the potential of some recently introduced molecules [4,5], the investigators had the need to realize a study to deepen the feasibility of a dual-therapy that permit to exclude NRTIs from the backbone, with the aim to prevent NRTIs-related long-term toxicity.

The investigators have designed a prospective randomized controlled trial, open-label, with a duration of 96 weeks, to compare the efficacy of a dual-therapy based on rilpivirine 25mg plus darunavir 800mg/ritonavir 100mg QD, in HIV-positive subjects with suppressed viremia from at least 3 months. In fact, there are a few data about association of these drugs, which it has been shown to be safe, well tolerated, and with a strong pharmacological synergy, without nucleos(t)idic backbone, while the necessity to minimize the costs toxicity-related is becoming increasingly compelling.

According to clinical experience and literature data, the investigators hope this study shows positive results in term of immune-virological efficacy, as well as in term of decrease of VACS index - a complex parameter which has the purpose to quantify general organic decay - and markers of lipid and bone metabolism, in group which receives dual-therapy versus the group with standard therapy.

Condition Intervention Phase
Human Immunodeficiency Virus
Drug: RPV + DRV/r
Drug: continue the PI/r-containing HAART.
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Strategic Study of Dual-therapy With Darunavir/Ritonavir and Rilpivirine QD Versus Triple-therapy in Patients With Suppressed Viral Load: Virological Efficacy and Evaluation of Non-HIV Related Morbidity.

Resource links provided by NLM:

Further study details as provided by Ospedale L. Sacco – Polo Universitario:

Primary Outcome Measures:
  • HIV-RNA < 50 cp/mL [ Time Frame: Week 48 ]
    Responders: HIV+ subjects with HIV-RNA < 50 cp/mL at week 48 according to the intention-to-treat (ITT-TLOVR) approach.

Secondary Outcome Measures:
  • ACTG grade III and IV events. [ Time Frame: over 96 weeks. ]
    Safety will be assessed through the number of ACTG grade III and IV in the specified safety parameters.

Estimated Enrollment: 132
Study Start Date: September 2014
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RPV + DRV/r
switch to RPV + DRV/r
Drug: RPV + DRV/r
Switch to dual HAART
Other Names:
  • RVP: rilpivirine; brand name: EdurantTM.
  • DRV: darunavir; brand name: PrezistaTM.
Active Comparator: continue the PI/r-containing HAART.
continue the PI/r-containing HAART
Drug: continue the PI/r-containing HAART.
Continue the on-going triple drug HAART.
Other Name: the drugs will depend on the successful regimen.

Detailed Description:

Pilot, phase III prospective, randomized, open-label, multicentric controlled study, which will offer a novel dual-therapy regimen including RPV 25mg + DRV 800mg/rtv 100mg QD to HIV+ subjects with suppressed viremia.

132 HIV+ subjects will be randomized, 1:1, to switch to RPV+DRV/r versus continue triple-drug therapy. Subjects will be switched from any PI/r-containing regimen.

The duration of the study is 96 weeks and patients will be stratified according to their HCV serostatus (Ab positive or negative), age (> or < 50 years), and immunological status (CD4<200/µL; CD4=200-500/µL; CD4>500/µL). It is planned to enroll at least 30% of female subjects.

Follow-up visits will be performed at 4, 8, 12, 24, 36, 48, 60, 72, and 96 weeks (laboratory and physical examination).

Effectiveness will be measured by determination of HIV-RNA, safety will be evaluated by determination of AST, ALT, creatinine, plasmatic and urinary phosphate, albuminuria, total cholesterol, HDL and LDL cholesterol, triglycerides at the follow-up visits.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adult HIV+ subjects (>18 years old), giving and signing an informed consent;
  • Any HAART treatment for at least 12 months;
  • Current treatment with a PI/r-containing regimen initiated at least 6 months earlier;
  • HIV-RNA <50 cp/mL for at least 3 months, without viral blip due to virologic failure at any time;
  • Any nadir CD4 lymphocytes;
  • Current CD4 count > 100 cell/uL;
  • eGFRs >60 mL/min/1.73 m2.

Exclusion Criteria:

  • Previous drug resistance genotypic test showing the presence of any RPV (RT: K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C, M230I/L) or DRV (protease: V11I, V32I, L33F, I47V, I50V, I54M/L, T74P, L76V, I84V, L89V) resistance associated mutation (RAM), according to the November 2011 IAS-USA list;
  • Child-Pugh C or grade 3-4 AST or ALT values;
  • Acute cardiovascular event within 6 months;
  • AIDS event within 6 months;
  • Current IVDU;
  • HBsAg +;
  • Pregnancy or lactation.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01792570

Contact: Stefano - Rusconi, M.D. 0039 02 39042949

Clinica delle Malattie Infettive, Policlinico Universitario Recruiting
Bari, BA, Italy
Contact: Gioacchino Angarano, M.D.   
Principal Investigator: Gioacchino Angarano, M.D.         
Divisione di Malattie Infettive, Ospedale S. Maria Annunziata, Antella Recruiting
Firenze, FI, Italy
Contact: Sergio Lo Caputo, M.D.   
Principal Investigator: Sergio Lo Caputo, M.D.         
Clinica delle Malattie Infettive, Ospedale San Martino, Università degli Studi Recruiting
Genova, GE, Italy
Contact: Antonio Di Biagio, M.D.   
Principal Investigator: Antonio Di Biagio, M.D.         
Divisione di Malattie Infettive, Ospedale San Gerardo Recruiting
Monza, MB, Italy
Contact: Andrea Gori, M.D.   
Principal Investigator: Andrea Gori, M.D.         
Divisione Clinicizzata di Malattie Infettive dell'Università degli Studi, Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco" Recruiting
Milano, MI, Italy, 20157
Contact: Stefano Rusconi, M.D.   
Contact: Elisa Colella, M.D.   
Principal Investigator: Stefano Rusconi, M.D.         
I e II Divisione Malattie Infettive, Azienda Ospedaliera-Polo Universitario "Luigi Sacco" Recruiting
Milano, MI, Italy, 20157
Contact: Giuliano Rizzardini, M.D.   
Principal Investigator: Giuliano Rizzardini, M.D.         
Clinica Malattie Infettive, Policlinico Universitario Not yet recruiting
Modena, MO, Italy
Contact: Cristina Mussini, M.D.   
Principal Investigator: Cristina Mussini, M.D.         
U.O. Malattie Infettive, Policlinico S. Matteo Recruiting
Pavia, PV, Italy
Contact: Renato Maserati, M.D.   
Principal Investigator: Renato Maserati, M.D.         
Clinica delle Malattie Infettive, Policlinico "Tor Vergata" Recruiting
Roma, RM, Italy
Contact: Massimo Andreoni, M.D.   
Contact: Loredana Sarmati, M.D.   
Principal Investigator: Massimo Andreoni, M.D.         
Istituto di Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore Not yet recruiting
Roma, RM, Italy
Contact: Simona Di Giambenedetto, M.D.   
Principal Investigator: Simona Di Giambenedetto, M.D.         
U.O. Malattie Infettive, Azienda Policlinico Umberto I, Università degli Studi "La Sapienza" Recruiting
Roma, RM, Italy
Contact: Vincenzo Vullo, M.D.   
Contact: Gabriella D'Ettorre, M.D.   
Principal Investigator: Vincenzo Vullo, M.D.         
Clinica delle Malattie Infettive, Ospedale Amedeo di Savoia, Università degli Studi Recruiting
Torino, TO, Italy
Contact: Stefano Bonora, M.D.   
Principal Investigator: Stefano Bonora, M.D.         
Sponsors and Collaborators
Ospedale L. Sacco – Polo Universitario
Elisa Colella, M.D.
Valentina Di Cristo, M.D.
Massimo Galli, M.D.
Principal Investigator: Stefano - Rusconi, M.D. DIBIC "Luigi Sacco", Università degli Studi di Milano, Italy
  More Information

Responsible Party: Stefano Rusconi, Associate professor in infectious diseases, Ospedale L. Sacco - Polo Universitario Identifier: NCT01792570     History of Changes
Other Study ID Numbers: HLS03/2012
Study First Received: February 7, 2013
Last Updated: March 29, 2016
Individual Participant Data  
Plan to Share IPD: Yes

Keywords provided by Ospedale L. Sacco – Polo Universitario:
strategic study

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
HIV Protease Inhibitors
Protease Inhibitors processed this record on April 25, 2017