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Population Effectiveness of Dolutegravir Implementation in Sub-Saharan Africa (DISCO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04066036
Recruitment Status : Recruiting
First Posted : August 22, 2019
Last Update Posted : August 28, 2019
Sponsor:
Collaborators:
Africa Health Research Institute
Mbarara University of Science and Technology
National Institute of Allergy and Infectious Diseases (NIAID)
Wellcome Trust
ViiV Healthcare
Harvard Medical School
University of KwaZulu
Emory University
Information provided by (Responsible Party):
Mark Siedner, Massachusetts General Hospital

Brief Summary:
This is a prospective observational cohort study enrolling participants in South Africa and Uganda who are prescribed an HIV treatment regimen containing lamivudine, tenofovir, and dolutegravir, which is known as TLD. We hope to better understand how effective TLD will be in sub-Saharan Africa. If treatment failure occurs, we seek to understand the possible reasons, including drug resistance and adherence challenges.

Condition or disease Intervention/treatment
HIV-1-infection Other: This is an observational study only.

Detailed Description:

This study is a prospective observational cohort study at three government-supported HIV clinics in rural South Africa and Uganda. We will enroll 1,000 adults living with HIV who are switched from first-line antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) to TLD. We will follow participants for one year with study visits at enrollment, 24 weeks, and 48 weeks. Study procedures include interviews, body measurements, chart review, and collection of blood and urine specimens for retrospective testing, including viral load, drug resistance testing, antiretroviral drug level testing, and tests to evaluate the effects of TLD on renal, liver, metabolic, and other organ function.

Aim 1: To determine the contributions of resistance prior to switch to TLD from a NNRTI-based regimen to risk of treatment failure after six and twelve months on TLD. Hypothesis: People living with HIV who experience virologic failure on TLD will have increased odds of NRTI mutations prior to TLD exposure, compared to controls with virologic suppression.

Aim 2: Explore pharmacologic measures of adherence to distinguish virologic failure on TLD due to suboptimal adherence versus resistance using 2a) urine tenofovir (TFV) levels and 2b) tenofovir diphosphate (TFV-DP) in dried blood spots (DBS). Hypothesis: Absence of TFV in urine and TFV-DP concentrations in DBS will distinguish ART failure with versus without resistance.

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Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Population Effectiveness of Dolutegravir Implementation in Sub-Saharan Africa: A Prospective Observational Cohort Study
Actual Study Start Date : May 14, 2019
Estimated Primary Completion Date : October 1, 2021
Estimated Study Completion Date : October 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Group/Cohort Intervention/treatment
Study Population
The study will enroll a total of 1,000 ART-experienced participants from the study sites in Uganda and South Africa who are being transitioned to TLD from non-nucleoside reverse transcriptase-based antiretroviral therapy.
Other: This is an observational study only.
This is an observational study only.




Primary Outcome Measures :
  1. Proportion of participants with virologic failure (HIV-1 RNA >= 200 copies/mL) [ Time Frame: 48 weeks ]
    HIV-1 RNA >= 200 copies/mL


Secondary Outcome Measures :
  1. Proportion of participants with virologic failure (HIV-1 RNA >= 1,000 copies/mL) [ Time Frame: 48 weeks ]
    HIV-1 RNA >= 1,000 copies/mL

  2. Proportion of participants with HIV drug resistance [ Time Frame: 24 and 48 weeks ]
    Proportion of participants with International AIDS Society-defined drug resistance mutations to their current regimen


Biospecimen Retention:   Samples With DNA
whole blood, buffy coat, plasma, urine


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
This study will enroll a total of 1,000 individuals from Uganda and South Africa, who are currently enrolled in care at one of the study clinics who have been taking NNRTI-based ART for a minimum of six months, and who are switching to TLD. 500 participants will be recruited from Uganda, and 500 will be recruited from South Africa.
Criteria

Inclusion Criteria:

  • Age ≥18 years
  • HIV-positive and in care at one of the study clinics
  • Current use of NNRTI-based, first-line ART for a minimum of 6 months
  • Prescribed change to TLD by clinic staff
  • Residing within 100 kilometers of the treatment clinic without plans to change permanent residence in the next 48 weeks
  • Consents to participation

Exclusion Criteria:

There are no specific exclusion criteria. Both men and women will be theoretically eligible. We note that decision to use TLD in patients at the recruitment clinic will be made by clinic staff, and referral for study procedures will not be made until after this decision is made. We also note that, as of the time of this protocol draft, TLD use might be limited to men, women of non-child bearing ages, and women confirmed to be on contraception. This study will follow both national guidelines and clinician discretion about use of TLD in the clinic population.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04066036


Contacts
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Contact: Suzanne M McCluskey, MD 617-726-3812 smccluskey@mgh.harvard.edu

Locations
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South Africa
Africa Health Research Institute Not yet recruiting
Somkele, KwaZulu-Natal, South Africa
Contact: Mark J Siedner, MD, MPH       msiedner@mgh.harvard.edu   
Uganda
Mbarara University of Science and Technology Recruiting
Mbarara, Uganda
Contact: Mwebesa B Bwana, MBChB       mwebesa_bwana@yahoo.com   
Contact: Winnie Muyindike, MBChB       wmuyindike@gmail.com   
Principal Investigator: Mwebesa B Bwana, MBChB         
Sub-Investigator: Winnie Muyindike, MBChB         
Sponsors and Collaborators
Massachusetts General Hospital
Africa Health Research Institute
Mbarara University of Science and Technology
National Institute of Allergy and Infectious Diseases (NIAID)
Wellcome Trust
ViiV Healthcare
Harvard Medical School
University of KwaZulu
Emory University
Investigators
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Principal Investigator: Suzanne M McCluskey, MD Massachusetts General Hospital
Principal Investigator: Mark J Siedner, MD, MPH Massachusetts General Hospital, Africa Health Research Institute
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Responsible Party: Mark Siedner, Associate Professor, Assistant Physician, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT04066036    
Other Study ID Numbers: 2019P000898-A
K23AI143470 ( U.S. NIH Grant/Contract )
212215 ( Other Grant/Funding Number: ViiV Healthcare )
WT108082AIA ( Other Grant/Funding Number: Wellcome Trust )
First Posted: August 22, 2019    Key Record Dates
Last Update Posted: August 28, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be made public and accessible through request after completion of the primary analysis.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Analytic Code
Time Frame: After completion of the primary analysis
Access Criteria: De-identified data and supporting information will be made available upon request after agreement among the principal investigators, and based on what is allowable in the study informed consent documents.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mark Siedner, Massachusetts General Hospital:
HIV Integrase Inhibitors
Sub-Saharan Africa
Anti-HIV Agents
Medication Adherence
Virologic Failure
Viral Drug Resistance
South Africa
Uganda
HIV-1