HIV InfectionPhase 3MOBIDIPNCT01905059
Evaluation of a Maintenance Strategy With Protease Inhibitors With or Without Lamivudine in Virologically Suppressed HIV Patients on Second Line Antiretroviral Treatment in Africa
A Phase 3 study testing monoPI - boosted lopinavir or boosted darunavir and bi therapy - (boosted lopinavir or boosted darunavir) + lamivudine in people with HIV Infection, run by ANRS, Emerging Infectious Diseases at 5 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection
- What is being tested?
- monoPI - boosted lopinavir or boosted darunavir and bi therapy - (boosted lopinavir or boosted darunavir) + lamivudine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 265 participants
- Where
- 5 sitesin 3 countries
- Study dates
- Feb 2014to Feb 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
About this study
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)
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.
Read the detailed description
Justification: The interest of treating HIV infection with a single molecule has been clear for a long time. Many clinical trials have been testing the efficacy of such a strategy, mainly using a boosted protease inhibitor (PI). Despite the remaining doubts about low level viremia, viral control in reservoirs, durability of the effect, the trials showed attractive results with an absolute increase in the risk of virological failure between 2% and 13% compared to the standard of care and a possible decrease in costs and toxicity.
In resource-limited countries the interest of treatment simplification is even more important: decrease in costs, toxicity (often poorly monitored), number of pills taken per day, etc. In addition, for patients in second line for whom some kind of resistance to NRTI is highly probable, the interruption of the second line NRTI could help to avoid the accumulation of mutations in the RT in the presence of residual low level replication, sparing future treatment options.
The 184 mutation of the retro-transcriptase which causes resistance to lamivudine/emtricitabine seems to hinder viral replication. The persistence of this mutation could eventually facilitate the action of PI monotherapy while protecting patients from further mutations. The choice of viral load (VL) threshold for the diagnosis of failure in resource-limited countries is not easy, the 2LADY trial used in clinical practice, the threshold of 1000 copies/ml which allows genotyping for evidence of mutations. This value will probably be selected as a reference value by the WHO in its next recommendations. To minimize the risk of viral escape and the development of resistances in the MOBIDIP study the threshold of 200 copies/ml has been chosen for the switch to monotherapy and of 500 copies/ml for the definition of failure.
Principal objective: To evaluate the failure rate at 96 weeks of a PI monotherapy with or without lamivudine, in HIV positive patients on second line treatment (ART) for at least 48 weeks, and with a VL of less than 200 copies/ml in Africa (Yaoundé, Bobo Dioulasso, Dakar).
Specific objectives: To evaluate:
- viral efficacy at a threshold of 50 copies/ml at 48 and 96 weeks,
- failure rate at 500 copies/ml after 24 weeks from the reintroduction of NRTI backbone in case of monotherapy failure,
- clinical and immunological outcomes,
- development of mutations,
- tolerance and impact on metabolic profile and
- neuro-cognitive disorders,
- adherence
Methods: 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. Failure is defined as: 1) viral load ≥500 copies/ml, 2) reintroduction of NRTI backbone, 3) interruption of the PI. A sample of 260 participants is planned.
Schedule: After approval by national Ethical committees and national authorities, patients followed in 2LADY trial for at least 48 weeks, and presenting the eligibility criteria, will stop their NRTI backbone and be randomized (over 6 months) to add or not lamivudine to their PI monotherapy. All patients will be followed for 96 weeks. In case of viral load above 500 copies/ml during the study, the original NRTI backbone will be re-introduced and the patient will be followed for an extra 24 weeks to verify viral response. The complete trial is due to last 3 years.
Expected results: This study will allow the validation of a maintenance strategy for patients in second line ART less expensive and toxic. In addition results could be used to guide clinical practice for physicians in resources poor countries
In march 2016 an interim analysis asked by the DSMB showed increased risk of failure in the monotherpay arm and the arm was stopped. Participant are switched on standard second line triple therapy and followed until Week 96. Participant on dual therapy continue their follow up. Comparative analysis are planned for data on week 60 visit (last visit with all participants on the randomized treatment).
- Conditions
- HIV Infection
- Being tested
- monoPI - boosted lopinavir or boosted darunavir, bi therapy - (boosted lopinavir or boosted darunavir) + lamivudine
- Keywords
- HIV infection, second line ART, maintenance strategies, Protease inhibitors, mono or bi-therapy
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
monoPI - boosted lopinavir or boosted darunavirDrug
Also called Protease Inhibitor monotherapy, boosted darunavir monotherapy, boosted lopinavir monotherapy
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.
bi therapy - (boosted lopinavir or boosted darunavir) + lamivudineDrug
Also called bi therapy, PI + 3TC, Boosted Protease Inhibitors plus lamivudine, LPV/r with lamivudine and DRV/r with 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. This arm is going on, patients will be followed on this intervention until the end of the study at week 96
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Drug: bi therapy - (boosted lopinavir or boosted darunavir) + lamivudine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 96 weeks
Secondary outcomes (10)
Treatment failure after reintroduction of the baseline NRTI backbone regimen
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
Measured: 24 weeks from reintroduction NRTI regimen
Virological response
Number of patient with VL < 50 copies/ml
Measured: 48 weeks
The viral resistance
The frequency of resistance mutations in the case of treatment failure
Measured: 24 weeks from reintroduction NRTI regimen
The clinical course of the HIV infection
Numbers of : AIDS events, non-AIDS events, death, adverse events
Measured: Inclusion to 96 weeks
The Immune response
The variation in the level of circulating CD4+ lymphocytes
Measured: Between the inclusion and 96 weeks
Tolerability
Changes to the parameters in baseline lipid profile, renal function and bone mineral density
Measured: Between the inclusion and 96 weeks
Assessment of the adherence
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.
Measured: 96 weeks but an average of mesures of each visits
Changes in anthropometric measures
Changes to the following anthropometric measurements: waist circumference, hip circumference and thigh circumference
Measured: between the inclusion and 96 weeks
Assessment neurocognitive functions
screening questions (EACS Guidelines)
Measured: 96 weeks
virological response
Number of patient with VL < 50 copies/ml
Measured: 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2013 (estimated)
- Study startFeb 2014
- Primary completionApr 2016
- Study completionFeb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by ANRS, Emerging Infectious DiseasesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 265 participants (actual)
Sponsor and investigators
- Lead sponsor
- ANRS, Emerging Infectious Diseases
- Sponsor type
- Other government
- Collaborators
- Janssen Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Koulla Shiro Sinata, Prof, Principal investigator, University of YaoundeSawadogo Adrien, Dr, Principal investigator, Hopital de Jour CHU Bobo DioulassoNdour Cheik Tidiane, Prof, Principal investigator, Service Maladies Infectieuses CHU Fann DakarCiaffi Laura, Dr, Principal investigator, UMI 233 IRD Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01905059
- Sponsor's protocol ID
- ANRS 12286MOBIDIP
- Acronym
- MOBIDIP
- Status last verified
- Jul 2017
- First submitted
- 15 Jul 2013
- Last updated
- 21 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 16249701Pulido 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.
PubMed 18097218Cameron 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.
PubMed 18540803Cahn 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.
PubMed 21886816Vernazza 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.
PubMed 17545707Gutmann 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.
PubMed 20802298Katlama 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.
PubMed 20802297Arribas 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.
PubMed 20010070Mathis 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.
PubMed 21811554Gilks 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.
PubMed 22814125Bartlett 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.
PubMed 22441252Castagna 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.
PubMed 16549962Bunupuradah 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.
PubMed 23075703Ciaffi 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.
PubMed 28566227
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01905059
- Acronym / sponsor ID
- MOBIDIP / ANRS 12286MOBIDIP
- Conditions
- HIV Infection
- Keywords
- HIV infection, second line ART, maintenance strategies, Protease inhibitors, mono or bi-therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 265 participants (actual)
- Lead sponsor
- ANRS, Emerging Infectious DiseasesOther government
- Collaborators
- Janssen Pharmaceuticals
- Study start
- Feb 2014
- Primary completion
- Apr 2016 (actual)
- Study completion
- Feb 2017 (actual)
- First posted
- 23 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Justification: The interest of treating HIV infection with a single molecule has been clear for a long time. Many clinical trials have been testing the efficacy of such a strategy, mainly using a boosted protease inhibitor (PI). Despite the remaining doubts about low level viremia, viral control in reservoirs, durability of the effect, the trials showed attractive results with an absolute increase in the risk of virological failure between 2% and 13% compared to the standard of care and a possible decrease in costs and toxicity.
In resource-limited countries the interest of treatment simplification is even more important: decrease in costs, toxicity (often poorly monitored), number of pills taken per day, etc. In addition, for patients in second line for whom some kind of resistance to NRTI is highly probable, the interruption of the second line NRTI could help to avoid the accumulation of mutations in the RT in the presence of residual low level replication, sparing future treatment options.
The 184 mutation of the retro-transcriptase which causes resistance to lamivudine/emtricitabine seems to hinder viral replication. The persistence of this mutation could eventually facilitate the action of PI monotherapy while protecting patients from further mutations. The choice of viral load (VL) threshold for the diagnosis of failure in resource-limited countries is not easy, the 2LADY trial used in clinical practice, the threshold of 1000 copies/ml which allows genotyping for evidence of mutations. This value will probably be selected as a reference value by the WHO in its next recommendations. To minimize the risk of viral escape and the development of resistances in the MOBIDIP study the threshold of 200 copies/ml has been chosen for the switch to monotherapy and of 500 copies/ml for the definition of failure.
Principal objective: To evaluate the failure rate at 96 weeks of a PI monotherapy with or without lamivudine, in HIV positive patients on second line treatment (ART) for at least 48 weeks, and with a VL of less than 200 copies/ml in Africa (Yaoundé, Bobo Dioulasso, Dakar).
Specific objectives: To evaluate:
- viral efficacy at a threshold of 50 copies/ml at 48 and 96 weeks,
- failure rate at 500 copies/ml after 24 weeks from the reintroduction of NRTI backbone in case of monotherapy failure,
- clinical and immunological outcomes,
- development of mutations,
- tolerance and impact on metabolic profile and
- neuro-cognitive disorders,
- adherence
Methods: 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. Failure is defined as: 1) viral load ≥500 copies/ml, 2) reintroduction of NRTI backbone, 3) interruption of the PI. A sample of 260 participants is planned.
Schedule: After approval by national Ethical committees and national authorities, patients followed in 2LADY trial for at least 48 weeks, and presenting the eligibility criteria, will stop their NRTI backbone and be randomized (over 6 months) to add or not lamivudine to their PI monotherapy. All patients will be followed for 96 weeks. In case of viral load above 500 copies/ml during the study, the original NRTI backbone will be re-introduced and the patient will be followed for an extra 24 weeks to verify viral response. The complete trial is due to last 3 years.
Expected results: This study will allow the validation of a maintenance strategy for patients in second line ART less expensive and toxic. In addition results could be used to guide clinical practice for physicians in resources poor countries
In march 2016 an interim analysis asked by the DSMB showed increased risk of failure in the monotherpay arm and the arm was stopped. Participant are switched on standard second line triple therapy and followed until Week 96. Participant on dual therapy continue their follow up. Comparative analysis are planned for data on week 60 visit (last visit with all participants on the randomized treatment).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| monoPI - boosted lopinavir or boosted darunavir | Active comparator | Drug: monoPI - boosted lopinavir or boosted darunavirboosted 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. |
| bi therapy - (boosted lopinavir or darunavir) + lamivudine | Active comparator | Drug: bi therapy - (boosted lopinavir or boosted darunavir) + lamivudineboosted 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| monoPI - boosted lopinavir or boosted darunavirAlso: Protease Inhibitor monotherapy, boosted darunavir monotherapy, boosted lopinavir monotherapyboosted 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. | Drug | monoPI - boosted lopinavir or boosted darunavir |
| bi therapy - (boosted lopinavir or boosted darunavir) + lamivudineAlso: bi therapy, PI + 3TC, Boosted Protease Inhibitors plus lamivudine, LPV/r with lamivudine and DRV/r with lamivudineboosted 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 | Drug | bi therapy - (boosted lopinavir or darunavir) + lamivudine |
Primary outcome
Proportion of patients in virological failure
Time frame: 96 weeks
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.
10 secondary outcomes
Treatment failure after reintroduction of the baseline NRTI backbone regimen
Time frame: 24 weeks from reintroduction NRTI regimen
Virological response
Time frame: 48 weeks
The viral resistance
Time frame: 24 weeks from reintroduction NRTI regimen
The clinical course of the HIV infection
Time frame: Inclusion to 96 weeks
The Immune response
Time frame: Between the inclusion and 96 weeks
Tolerability
Time frame: Between the inclusion and 96 weeks
Assessment of the adherence
Time frame: 96 weeks but an average of mesures of each visits
Changes in anthropometric measures
Time frame: between the inclusion and 96 weeks
Assessment neurocognitive functions
Time frame: 96 weeks
virological response
Time frame: 96 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2017.
- Background: PubMed 16249701Arribas 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.
- Background: PubMed 18097218Pulido 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.
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- Sponsor siteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Koulla Shiro Sinata, Prof principal investigator
University of Yaounde
Sawadogo Adrien, Dr principal investigator
Hopital de Jour CHU Bobo Dioulasso
Ndour Cheik Tidiane, Prof principal investigator
Service Maladies Infectieuses CHU Fann Dakar
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing monoPI - boosted lopinavir or boosted darunavir and bi therapy - (boosted lopinavir or boosted darunavir) + lamivudine in people with HIV Infection, run by ANRS, Emerging Infectious Diseases at 5 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Cameroon, Senegal, Burkina Faso. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients in virological failure (time frame: 96 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01905059, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2017.