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)

July 19, 2017 updated by: ANRS, Emerging Infectious Diseases

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.

Study Overview

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 Type

Interventional

Enrollment (Actual)

265

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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)

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.

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.
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
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
Other Names:
  • bi therapy
  • PI + 3TC
  • Boosted Protease Inhibitors plus lamivudine
  • LPV/r with lamivudine and DRV/r with lamivudine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
96 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment failure after reintroduction of the baseline NRTI backbone regimen
Time Frame: 24 weeks from reintroduction NRTI 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
24 weeks from reintroduction NRTI regimen
Virological response
Time Frame: 48 weeks
Number of patient with VL < 50 copies/ml
48 weeks
The viral resistance
Time Frame: 24 weeks from reintroduction NRTI regimen
The frequency of resistance mutations in the case of treatment failure
24 weeks from reintroduction NRTI regimen
The clinical course of the HIV infection
Time Frame: Inclusion to 96 weeks
Numbers of : AIDS events, non-AIDS events, death, adverse events
Inclusion to 96 weeks
The Immune response
Time Frame: Between the inclusion and 96 weeks
The variation in the level of circulating CD4+ lymphocytes
Between the inclusion and 96 weeks
Tolerability
Time Frame: Between the inclusion and 96 weeks
Changes to the parameters in baseline lipid profile, renal function and bone mineral density
Between the inclusion and 96 weeks
Assessment of the adherence
Time Frame: 96 weeks but an average of mesures of each visits

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.

96 weeks but an average of mesures of each visits
Changes in anthropometric measures
Time Frame: between the inclusion and 96 weeks
Changes to the following anthropometric measurements: waist circumference, hip circumference and thigh circumference
between the inclusion and 96 weeks
Assessment neurocognitive functions
Time Frame: 96 weeks
screening questions (EACS Guidelines)
96 weeks
virological response
Time Frame: 96 weeks
Number of patient with VL < 50 copies/ml
96 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (Actual)

April 1, 2016

Study Completion (Actual)

February 1, 2017

Study Registration Dates

First Submitted

July 15, 2013

First Submitted That Met QC Criteria

July 22, 2013

First Posted (Estimate)

July 23, 2013

Study Record Updates

Last Update Posted (Actual)

July 21, 2017

Last Update Submitted That Met QC Criteria

July 19, 2017

Last Verified

July 1, 2017

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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