Human Immunodeficiency Virus Clinical Trial
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.
Verified date | March 2020 |
Source | ASST Fatebenefratelli Sacco |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 37 |
Est. completion date | December 31, 2018 |
Est. primary completion date | December 31, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
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. |
Country | Name | City | State |
---|---|---|---|
Italy | Clinica delle Malattie Infettive, Policlinico Universitario | Bari | BA |
Italy | Divisione di Malattie Infettive, Ospedale S. Maria Annunziata, Antella | Firenze | FI |
Italy | Clinica delle Malattie Infettive, Ospedale San Martino, Università degli Studi | Genova | GE |
Italy | Divisione Clinicizzata di Malattie Infettive dell'Università degli Studi, Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco" | Milano | MI |
Italy | I e II Divisione Malattie Infettive, Azienda Ospedaliera-Polo Universitario "Luigi Sacco" | Milano | MI |
Italy | Clinica Malattie Infettive, Policlinico Universitario | Modena | MO |
Italy | Divisione di Malattie Infettive, Ospedale San Gerardo | Monza | MB |
Italy | U.O. Malattie Infettive, Policlinico S. Matteo | Pavia | PV |
Italy | Clinica delle Malattie Infettive, Policlinico "Tor Vergata" | Roma | RM |
Italy | Istituto di Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore | Roma | RM |
Italy | U.O. Malattie Infettive, Azienda Policlinico Umberto I, Università degli Studi "La Sapienza" | Roma | RM |
Italy | Clinica delle Malattie Infettive, Ospedale Amedeo di Savoia, Università degli Studi | Torino | TO |
Lead Sponsor | Collaborator |
---|---|
ASST Fatebenefratelli Sacco | Elisa Colella, M.D., Massimo Galli, M.D., Valentina Di Cristo, M.D. |
Italy,
Broder S. The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic. Antiviral Res. 2010 Jan;85(1):1-18. doi: 10.1016/j.antiviral.2009.10.002. Epub 2009 Dec 16. Review. — View Citation
Burgos J, Crespo M, Falcó V, Curran A, Imaz A, Domingo P, Podzamczer D, Mateo MG, Van den Eynde E, Villar S, Ribera E. Dual therapy based on a ritonavir-boosted protease inhibitor as a novel salvage strategy for HIV-1-infected patients on a failing antiretroviral regimen. J Antimicrob Chemother. 2012 Jun;67(6):1453-8. doi: 10.1093/jac/dks057. Epub 2012 Feb 29. — View Citation
Clumeck N, Cahn P, Molina JM, Mills A, Nijs S, Vingerhoets J, Witek J. Virological response with fully active etravirine: pooled results from the DUET-1 and DUET-2 trials. Int J STD AIDS. 2010 Nov;21(11):738-40. doi: 10.1258/ijsa.2010.010139. — View Citation
Earley A, Miskulin D, Lamb EJ, Levey AS, Uhlig K. Estimating equations for glomerular filtration rate in the era of creatinine standardization: a systematic review. Ann Intern Med. 2012 Jun 5;156(11):785-95, W-270, W-271, W-272, W-273, W-274, W-275, W-276, W-277, W-278. doi: 10.7326/0003-4819-156-6-201203200-00391. Epub 2012 Feb 6. Review. — View Citation
Maggi P, Bartolozzi D, Bonfanti P, Calza L, Cherubini C, Di Biagio A, Marcotullio S, Montella F, Montinaro V, Mussini C, Narciso P, Rusconi S, Vescini F. Renal complications in HIV disease: between present and future. AIDS Rev. 2012 Jan-Mar;14(1):37-53. Review. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | HIV-RNA < 50 cp/mL | Responders: HIV+ subjects with HIV-RNA < 50 cp/mL at week 48 according to the intention-to-treat (ITT-TLOVR) approach. | Week 48 | |
Secondary | ACTG grade III and IV events. | Safety will be assessed through the number of ACTG grade III and IV in the specified safety parameters. | over 96 weeks. |
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