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

NCT01905059 | Completed Phase 3 DMC

• 1 other identifier: ANRS 12286MOBIDIP
• Study Type: interventional
• Target: 265
• Locations: 3 countries
• Sites: 5

Brief Summary

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.

Conditions

HIV Infection

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Proportion of patients in virological failure

  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.

  96 weeks

Secondary Outcomes (10)

• Treatment failure after reintroduction of the baseline NRTI backbone regimen

  24 weeks from reintroduction NRTI regimen

• Virological response

  48 weeks

• The viral resistance

  24 weeks from reintroduction NRTI regimen

• The clinical course of the HIV infection

  Inclusion to 96 weeks

• The Immune response

  Between the inclusion and 96 weeks

Study Arms (2)

monoPI - boosted lopinavir or boosted darunavir

ACTIVE COMPARATOR

boosted lopinavir (LPV/rtv 200/50 mg 2 tbs BID) or boosted darunavir (DRV 400 mg 2 tbs plus RTV 100 mg QD) This arm has been stopped on advise of DSMB (approved by Scientific Committee), patients are switched to standard second line triple therapy and followed until the end of the study at week 96.

Drug: monoPI - boosted lopinavir or boosted darunavir

bi therapy - (boosted lopinavir or darunavir) + lamivudine

ACTIVE COMPARATOR

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

Interventions

monoPI - boosted lopinavir or boosted darunavir DRUG

boosted lopinavir (LPV/rtv 200/50 mg 2 tbs BID) or boosted darunavir (DRV 400 mg 2 tbs plus RTV 100 mg QD) This arm was stopped by the Scientific Committee on advise of the DSMB after interim analysis showing increased risk of failure for these participants. Participants are switched to standard second line triple therapy and will be followed until the last visit at week 96.

Also known as: Protease Inhibitor monotherapy, boosted darunavir monotherapy, boosted lopinavir monotherapy

monoPI - boosted lopinavir or boosted darunavir

bi therapy - (boosted lopinavir or boosted darunavir) + lamivudine DRUG

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. This arm is going on, patients will be followed on this intervention until the end of the study at week 96

Also known as: bi therapy, PI + 3TC, Boosted Protease Inhibitors plus lamivudine, LPV/r with lamivudine and DRV/r with lamivudine

bi therapy - (boosted lopinavir or darunavir) + lamivudine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (5)

Day Care Center CHU Sanou Sauro

Bobo-Dioulasso, Burkina Faso

Location

Central Hospital

Yaoundé, Cameroon

Location

Military Hospital

Yaoundé, Cameroon

Location

CRCF Hopital de Fann

Dakar, Senegal

Location

CTA CHU de Fann

Dakar, Senegal

Location

Related Publications (14)

• Arribas JR, Pulido F, Delgado R, Lorenzo A, Miralles P, Arranz A, Gonzalez-Garcia JJ, Cepeda C, Hervas R, Pano JR, Gaya F, Carcas A, Montes ML, Costa JR, Pena 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. doi: 10.1097/01.qai.0000180077.59159.f4.

  PMID: 16249701 BACKGROUND

• Pulido F, Arribas JR, Delgado R, Cabrero E, Gonzalez-Garcia J, Perez-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. doi: 10.1097/QAD.0b013e3282f4243b.

  PMID: 18097218 BACKGROUND

• 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.

  PMID: 18540803 BACKGROUND

• Cahn P, Montaner J, Junod P, Patterson P, Krolewiecki A, Andrade-Villanueva J, Cassetti I, Sierra-Madero J, Casiro 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.

  PMID: 21886816 BACKGROUND

• 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. doi: 10.1097/QAD.0b013e32814e6b1c.

  PMID: 17545707 BACKGROUND

• Gutmann C, Cusini A, Gunthard 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.

  PMID: 20802298 BACKGROUND

• 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.

  PMID: 20802297 BACKGROUND

• Arribas JR, Horban A, Gerstoft J, Fatkenheuer 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.

  PMID: 20010070 BACKGROUND

• 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.

  PMID: 21811554 BACKGROUND

• 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.

  PMID: 22814125 BACKGROUND

• 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.

  PMID: 22441252 BACKGROUND

• 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. doi: 10.1097/01.aids.0000218542.08845.b2.

  PMID: 16549962 BACKGROUND

• Bunupuradah T, Chetchotisakd P, Ananworanich J, Munsakul W, Jirajariyavej S, Kantipong P, Prasithsirikul W, Sungkanuparph S, Bowonwatanuwong C, Klinbuayaem V, Kerr SJ, Sophonphan J, Bhakeecheep S, Hirschel B, Ruxrungtham K; HIV STAR Study Group. A randomized comparison of second-line lopinavir/ritonavir monotherapy versus tenofovir/lamivudine/lopinavir/ritonavir in patients failing NNRTI regimens: the HIV STAR study. Antivir Ther. 2012;17(7):1351-61. doi: 10.3851/IMP2443. Epub 2012 Jul 2.

  PMID: 23075703 BACKGROUND

• Ciaffi L, Koulla-Shiro S, Sawadogo AB, Ndour CT, Eymard-Duvernay S, Mbouyap PR, Ayangma L, Zoungrana J, Gueye NFN, Diallo M, Izard S, Bado G, Kane CT, Aghokeng AF, Peeters M, Girard PM, Le Moing V, Reynes J, Delaporte E; MOBIDIP study group. Boosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for HIV-1-infected patients in sub-Saharan Africa (ANRS12 286/MOBIDIP): a multicentre, randomised, parallel, open-label, superiority trial. Lancet HIV. 2017 Sep;4(9):e384-e392. doi: 10.1016/S2352-3018(17)30069-3. Epub 2017 May 28.

  PMID: 28566227 DERIVED

Related Links

• Sponsor site

MeSH Terms

Conditions

HIV Infections

Interventions

Lamivudine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2013
• First Posted: July 23, 2013
• Study Start: February 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: February 1, 2017
• Last Updated: July 21, 2017

Record last verified: 2017-07

Locations

BU (1); SE (2); CA (2)