Evaluation of a Maintenance Strategy With Protease Inhibitors With or Without Lamivudine in Virologically Suppressed HIV Patients on Second Line Antiretroviral Treatment in Africa - Full Text View

Purpose

Multicenter, randomized, superiority trial to evaluate efficacy of a mono or bi-therapy of protease inhibitors with or without lamivudine over a period of 96 weeks. The primary outcome will be the failure rate at 96 weeks. This study will include 260 participants, former participants of the 2LADY trial. It will be carried out in Yaoundé, Bobo Dioulasso and Dakar.

Condition	Intervention	Phase
HIV Infection	Drug: monoPI - boosted lopinavir or boosted darunavir Drug: bi therapy - (boosted lopinavir or boosted darunavir) + lamivudine	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Multicenter, International, Prospective, Phase III, Randomized, Superiority Trial Comparing Two Maintenance Strategies With Mono or Bi-therapy of Protease Inhibitors With or Without Lamivudine in Virologically Suppressed HIV Patients on Second Line Antiretroviral Treatment Over a Period of 96 Weeks in Africa (Dakar, Bobo Dioulasso, Yaounde)

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Proteinase inhibitor Lamivudine Lopinavir Darunavir Darunavir ethanolate

U.S. FDA Resources

Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:

Proportion of patients in virological failure [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
Number of patients with a treatment failure. Definition of treatment failure: 1) viral load ≥ 500 copies/ml confirmed in 2 samples with 1 month interval, or 2) the reintroduction of the two NRTIs or 3) interruption of the boosted PI.

Secondary Outcome Measures:

Treatment failure after reintroduction of the baseline NRTI backbone regimen [ Time Frame: 24 weeks from reintroduction NRTI regimen ] [ Designated as safety issue: No ]
Number of patients in virological failure after reintroduction NRTI regimen. Treatment failure defined by viral load > 200 and/or > 500 copies/ml within 24 weeks from the reintroduction of the baseline NRTI backbone regimen
Virological response [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Number of patient with VL < 50 copies/ml
The viral resistance [ Time Frame: 24 weeks from reintroduction NRTI regimen ] [ Designated as safety issue: No ]
The frequency of resistance mutations in the case of treatment failure
The clinical course of the HIV infection [ Time Frame: Inclusion to 96 weeks ] [ Designated as safety issue: No ]
Numbers of : AIDS events, non-AIDS events, death, adverse events
The Immune response [ Time Frame: Between the inclusion and 96 weeks ] [ Designated as safety issue: No ]
The variation in the level of circulating CD4+ lymphocytes
Tolerability [ Time Frame: Between the inclusion and 96 weeks ] [ Designated as safety issue: Yes ]
Changes to the parameters in baseline lipid profile, renal function and bone mineral density
Assessment of the adherence [ Time Frame: 96 weeks but an average of mesures of each visits ] [ Designated as safety issue: No ]
Adherence is considered high if consumption is greater than or equal to 95%, average if it is between 80 and 95% and low if it is less than 80%.

It is measured at each visit, by means of a questionnaire and by tablet count.
Changes in anthropometric measures [ Time Frame: between the inclusion and 96 weeks ] [ Designated as safety issue: Yes ]
Changes to the following anthropometric measurements: waist circumference, hip circumference and thigh circumference
Assessment neurocognitive functions [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
screening questions (EACS Guidelines)
virological response [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
Number of patient with VL < 50 copies/ml


Estimated Enrollment:	264
Study Start Date:	February 2014
Estimated Study Completion Date:	February 2017
Estimated Primary Completion Date:	August 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: monoPI - boosted lopinavir or boosted darunavir boosted lopinavir (LPV/rtv 200/50 mg 2 tbs BID) or boosted darunavir (DRV 400 mg 2 tbs plus RTV 100 mg QD)	Drug: monoPI - boosted lopinavir or boosted darunavir boosted lopinavir (LPV/rtv 200/50 mg 2 tbs BID) or boosted darunavir (DRV 400 mg 2 tbs plus RTV 100 mg QD) Other Names: Protease Inhibitor monotherapy boosted darunavir monotherapy boosted lopinavir monotherapy
Active Comparator: bi therapy - (boosted lopinavir or darunavir) + lamivudine boosted lopinavir (LPV/rtv 200/50 mg 2 tbs BID) with lamivudine 300 mg QD or boosted darunavir (DRV 400 mg 2 tbs plus RTV 100 mg QD)with lamivudine 300 mg QD	Drug: bi therapy - (boosted lopinavir or boosted darunavir) + lamivudine boosted lopinavir (LPV/rtv 200/50 mg 2 tbs BID) with lamivudine 300 mg QD or boosted darunavir (DRV 400 mg 2 tbs plus RTV 100 mg QD)with lamivudine 300 mg QD Other Names: bi therapy PI + 3TC Boosted Protease Inhibitors plus lamivudine LPV/r with lamivudine and DRV/r with lamivudine

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Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV infection on second line treatment in the 2lady trial for at least 48 weeks
VL ≤ 200 copies/ml since at least 6 months
No change in ART in the last 3 months previous to the study
CD4> 100 cells/ml
Signed informed consent
Adherence >90

Exclusion Criteria:

Previous viral failure (at least 2 consecutive HIV RNA >1000 copies/ml) while receiving a PI
Ongoing pregnancy and breast feeding women
HBsAg positive patients
opportunistic infection or any severe or progressive disease ongoing or treated in the 3 months before screening
Subject who in the investigator's opinion is unable to complete the study
History or symptoms of HIV encephalopathy

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 ClinicalTrials.gov identifier: NCT01905059

Contacts


Contact: Ciaffi Laura, Dr	0033 467 41 62 97	laura.ciaffi@ird.fr

Locations


Burkina Faso
Day Care Center CHU Sanou Sauro	Recruiting
Bobo Dioulasso, Burkina Faso
Cameroon
Central Hospital	Recruiting
Yaounde, Cameroon
Military Hospital	Recruiting
Yaounde, Cameroon
Senegal
CRCF Hopital de Fann	Completed
Dakar, Senegal
CTA CHU de Fann	Completed
Dakar, Senegal

Sponsors and Collaborators

French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Janssen Pharmaceuticals

Investigators


Principal Investigator:	Koulla Shiro Sinata, Prof	University of Yaounde
Principal Investigator:	Sawadogo Adrien, Dr	Hopital de Jour CHU Bobo Dioulasso
Principal Investigator:	Ndour Cheik Tidiane, Prof	Service Maladies Infectieuses CHU Fann Dakar
Principal Investigator:	Ciaffi Laura, Dr	UMI 233 IRD Montpellier

More Information

Additional Information:

Sponsor site This link exits the ClinicalTrials.gov site

Publications:

Arribas JR, Pulido F, Delgado R, Lorenzo A, Miralles P, Arranz A, González-García JJ, Cepeda C, Hervás R, Paño JR, Gaya F, Carcas A, Montes ML, Costa JR, Peña JM. Lopinavir/ritonavir as single-drug therapy for maintenance of HIV-1 viral suppression: 48-week results of a randomized, controlled, open-label, proof-of-concept pilot clinical trial (OK Study). J Acquir Immune Defic Syndr. 2005 Nov 1;40(3):280-7.

Pulido F, Arribas JR, Delgado R, Cabrero E, González-García J, Pérez-Elias MJ, Arranz A, Portilla J, Pasquau J, Iribarren JA, Rubio R, Norton M; OK04 Study Group. Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and two nucleosides for maintenance therapy of HIV. AIDS. 2008 Jan 11;22(2):F1-9.

Cameron DW, da Silva BA, Arribas JR, Myers RA, Bellos NC, Gilmore N, King MS, Bernstein BM, Brun SC, Hanna GJ. A 96-week comparison of lopinavir-ritonavir combination therapy followed by lopinavir-ritonavir monotherapy versus efavirenz combination therapy. J Infect Dis. 2008 Jul 15;198(2):234-40. doi: 10.1086/589622.

Cahn P, Montaner J, Junod P, Patterson P, Krolewiecki A, Andrade-Villanueva J, Cassetti I, Sierra-Madero J, Casiró AD, Bortolozzi R, Lupo SH, Longo N, Rampakakis E, Ackad N, Sampalis JS. Pilot, randomized study assessing safety, tolerability and efficacy of simplified LPV/r maintenance therapy in HIV patients on the 1 PI-based regimen. PLoS One. 2011;6(8):e23726. doi: 10.1371/journal.pone.0023726. Epub 2011 Aug 19.

Vernazza P, Daneel S, Schiffer V, Decosterd L, Fierz W, Klimkait T, Hoffmann M, Hirschel B. The role of compartment penetration in PI-monotherapy: the Atazanavir-Ritonavir Monomaintenance (ATARITMO) Trial. AIDS. 2007 Jun 19;21(10):1309-15.

Gutmann C, Cusini A, Günthard HF, Fux C, Hirschel B, Decosterd LA, Cavassini M, Yerly S, Vernazza PL; Swiss HIV Cohort Study (SHCS). Randomized controlled study demonstrating failure of LPV/r monotherapy in HIV: the role of compartment and CD4-nadir. AIDS. 2010 Sep 24;24(15):2347-54. doi: 10.1097/QAD.0b013e32833db9a1.

Katlama C, Valantin MA, Algarte-Genin M, Duvivier C, Lambert-Niclot S, Girard PM, Molina JM, Hoen B, Pakianather S, Peytavin G, Marcelin AG, Flandre P. Efficacy of darunavir/ritonavir maintenance monotherapy in patients with HIV-1 viral suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136. AIDS. 2010 Sep 24;24(15):2365-74. doi: 10.1097/QAD.0b013e32833dec20.

Arribas JR, Horban A, Gerstoft J, Fätkenheuer G, Nelson M, Clumeck N, Pulido F, Hill A, van Delft Y, Stark T, Moecklinghoff C. The MONET trial: darunavir/ritonavir with or without nucleoside analogues, for patients with HIV RNA below 50 copies/ml. AIDS. 2010 Jan 16;24(2):223-30. doi: 10.1097/QAD.0b013e3283348944.

Mathis S, Khanlari B, Pulido F, Schechter M, Negredo E, Nelson M, Vernazza P, Cahn P, Meynard JL, Arribas J, Bucher HC. Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis. PLoS One. 2011;6(7):e22003. doi: 10.1371/journal.pone.0022003. Epub 2011 Jul 19. Review.

Gilks CF, Walker AS, Dunn DT, Gibb DM, Kikaire B, Reid A, Musana H, Mambule I, Kasirye R, Robertson V, Ssali F, Spyer M, Pillay D, Yirrell D, Kaleebu P; DART Virology Group and Trial Team. Lopinavir/ritonavir monotherapy after 24 weeks of second-line antiretroviral therapy in Africa: a randomized controlled trial (SARA). Antivir Ther. 2012;17(7):1363-73. doi: 10.3851/IMP2253. Epub 2012 Jul 19.

Bartlett JA, Ribaudo HJ, Wallis CL, Aga E, Katzenstein DA, Stevens WS, Norton MR, Klingman KL, Hosseinipour MC, Crump JA, Supparatpinyo K, Badal-Faesen S, Kallungal BA, Kumarasamy N. Lopinavir/ritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings. AIDS. 2012 Jul 17;26(11):1345-54. doi: 10.1097/QAD.0b013e328353b066.

Castagna A, Danise A, Menzo S, Galli L, Gianotti N, Carini E, Boeri E, Galli A, Cernuschi M, Hasson H, Clementi M, Lazzarin A. Lamivudine monotherapy in HIV-1-infected patients harbouring a lamivudine-resistant virus: a randomized pilot study (E-184V study). AIDS. 2006 Apr 4;20(6):795-803.


Responsible Party:	French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier:	NCT01905059 History of Changes
Other Study ID Numbers:	ANRS 12286MOBIDIP
Study First Received:	July 15, 2013
Last Updated:	November 3, 2014
Health Authority:	Cameroon: Health Operational Reserach Division, MOH Cameroon Burkina Faso: Ministry of Health Burkina Faso: Ministère de la recherche scientifique et de l'innovation Burkina Faso: Comité d'Ethique pour la Recherche en Santé Senegal: Ministere de la santé et de l'action sociale Senegal: Comité National d'Ethique pour la Recherche en Santé Senegal: Comité National de Lutte contre le SIDA

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):


HIV infection second line ART maintenance strategies Protease inhibitors mono or bi-therapy

Additional relevant MeSH terms:


HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Virus Diseases Darunavir HIV Protease Inhibitors Lamivudine	Lopinavir Protease Inhibitors Anti-HIV Agents Anti-Infective Agents Anti-Retroviral Agents Antiviral Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Nucleic Acid Synthesis Inhibitors Pharmacologic Actions Reverse Transcriptase Inhibitors Therapeutic Uses

ClinicalTrials.gov processed this record on March 01, 2015

Evaluation of a Maintenance Strategy With Protease Inhibitors With or Without Lamivudine in Virologically Suppressed HIV Patients on Second Line Antiretroviral Treatment in Africa (MOBIDIP)