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)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Janssen Pharmaceuticals
Information provided by (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
First received: July 15, 2013
Last updated: July 18, 2014
Last verified: July 2014

July 15, 2013
July 18, 2014
February 2014
August 2016   (final data collection date for primary outcome measure)
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.
Proportion 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 PI/r.
Complete list of historical versions of study NCT01905059 on ClinicalTrials.gov Archive Site
  • 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
  • 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 patient failure after reintroduction NRTI regimen. Treatment failure defined by viral load > 200 and > 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: 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 the 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
Not Provided
Not Provided
 
Evaluation of a Maintenance Strategy With Protease Inhibitors With or Without Lamivudine in Virologically Suppressed HIV Patients on Second Line Antiretroviral Treatment in Africa
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.

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

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infection
  • 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
  • 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
  • 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)
    Intervention: Drug: monoPI - boosted lopinavir or boosted darunavir
  • 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
    Intervention: Drug: bi therapy - (boosted lopinavir or boosted darunavir) + lamivudine

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
264
February 2017
August 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Burkina Faso,   Cameroon,   Senegal
 
NCT01905059
ANRS 12286MOBIDIP
Yes
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Janssen Pharmaceuticals
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
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP