Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Impact of HIV Drug Resistance Testing, and Subsequent Change to an Individualized Therapy in Tanzania

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03557021
Recruitment Status : Unknown
Verified June 2018 by Dr. Christa Kasang, Medical Mission Institute, Germany.
Recruitment status was:  Recruiting
First Posted : June 14, 2018
Last Update Posted : June 14, 2018
Sponsor:
Collaborator:
National Institute for Medical Research, Tanzania
Information provided by (Responsible Party):
Dr. Christa Kasang, Medical Mission Institute, Germany

Brief Summary:

The current therapy regimens in Sub-Saharan countries, consisting of standardized first and second line drug combinations, yield a high rate of treatment failure, even within the first 12 months of therapy (23). These and other facts hint at the need for HIV resistance testing to improve treatment outcomes in resource-limited settings, but no prospective clinical data about this intervention exists. The proposed study aims to evaluate the impact of HIV drug resistance testing, and subsequent change to an individualized (second-line) therapy based on the resistance profile, in Tanzanian patients (children, adolescents and adults) with virological failure of their first-line and second-line therapy. Additionally, prevalence, patterns and clinical impact of HIVDR will be assessed, as well as the effect of enhanced adherence counselling.

The results of this study will help doctors to take evidence-based diagnostic and therapeutic decisions at an individual level, and will inform policy-makers in their decisions about future treatment and management concepts for HIV/AIDS.


Condition or disease Intervention/treatment Phase
HIV Drug Resistance Diagnostic Test: HIV Drug resistance testing Not Applicable

Detailed Description:

HIV/AIDS is one of the main health challenges of our time, with a global burden of disease higher than any other infectious disease. The widespread use of antiretroviral drugs has changed its face from a fatal fate to a chronic disease. However, there are still many differences in the standard of care globally. Drug resistance testing is routinely performed in high income countries, but is often not available in resource limited settings. Instead, treatment consists of standardized therapy regimes, chosen from a limited amount of antiretroviral drugs. This may contribute to the high rates of virological failure seen in patients, and especially children and adolescents, on therapy. Virological failure persisting despite intensified enhanced adherence-counselling result in poor treatment success in HIV infected adults, children and adolescents on treatment and therefore early deaths. If therapy failure occurs, and HIV drug resistance is the likely reason, physician in Tanzania need to blindly choose a second-line therapy regimen, without knowledge of the exact resistance profile. However, multiple studies have discovered high rates of HIV drug resistance in patients with first line treatment failure, and even in therapy-naïve patients. To obtain information about presence of resistance mutations HIV genotypic resistance testing is required. This test is used to detect HIV genomic mutations that confer resistance to specific types of antiretroviral drugs as an aid in monitoring and treating HIV-infection. The test identifies mutation on the protease and reverse transcriptase gene, which are responsible for very crucial steps in the viral replication process. Results from this test can identify the medication for whom the virus is still susceptible and for whom it is already resistant. With this, it can be avoid switching to second-line regimen without the knowledge of the presence or absence of antiretroviral drug resistance. An individualized therapy can follow making sure that medication works best and the clinical outcome can increase.

While the positive impact of HIV resistance testing on treatment outcomes in high-income countries is well established, no prospective data has been published about the effect in resource-limited settings. This absence of data poses a hole in clinical knowledge, because the results from high-income countries are not readily transferable to low-income settings.

The proposed study aims to evaluate the impact of HIV drug resistance testing, and subsequent change to an individualized (second-line) therapy based on the resistance profile, compared to standardized second-line therapy. The study is designed as a randomised controlled trial. The study participants, Tanzanian patients (children, adolescents and adults) with virological failure of their first-line therapy, will be recruited at several study sites. All patients will first receive enhanced adherence counselling. The patients that still show virological failure three months after the counselling will be eligible for resistance testing. The regimen will be switched to individualized (second-line) ART or standardized second-line ART, and clinical, immunological and virological outcome parameters will be collected in a 6 month and 12 month follow up visit (Group I,II,III IV). In addition to the outcome of individualized therapy, the proposed study would yield insights about the prevalence and patterns of HIV drug resistance in patients with failure of their first-line therapy, and also about the effectiveness of enhanced adherence counselling.

For ethical reasons also 250 seconnd line treatment failure patients (Group V) with fast clinical progress will be included and transfered directly to the individualized therapy arm. With that we hope to bring them back to a working treatment.

The main diagnostic method of this study, HIV genomic sequencing, will be implemented and performed at the National Institute for Medical Research in Mwanza, Tanzania. This will contribute directly to the HIV-related diagnostic capacities of Tanzanian laboratories.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Case control study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Impact of HIV Drug Resistance Testing, and Subsequent Change to an Individualized Therapy Based on the Resistance Profile, in Children, Adolescents and Adults With Virological Failure of Their HIV Therapy, in Three HIV Clinics in Tanzania
Actual Study Start Date : July 1, 2017
Estimated Primary Completion Date : September 30, 2019
Estimated Study Completion Date : September 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Individualized therapy arm
HIV Treatment failure patients will undergo an HIV Drug resistance testing and the followed therapy will be adjusted with in this setting available medications to the outcome of the resistance profile
Diagnostic Test: HIV Drug resistance testing
HIV Drug resistance testing by HIV pro DNA sanger sequencing

Active Comparator: standard therapy arm
HIV Treatment failure patients will undergo an HIV Drug resistance testing and the national defined standard therapy will be applied as second line treatment.
Diagnostic Test: HIV Drug resistance testing
HIV Drug resistance testing by HIV pro DNA sanger sequencing




Primary Outcome Measures :
  1. Viral Load [ Time Frame: 12 month ]
    Viral load will be measured by plasma HIV viral load measurement (copies per ml) after switching first-line treatment failure patients to individualized therapy compared to standard second line therapy.


Secondary Outcome Measures :
  1. Incidence of HIV related adverse events at 6 month [ Time Frame: 6 month ]
    HIV related adverse events at 6 month will be determined according to CTC AE list version 4

  2. Incidence of HIV related adverse events at at 12 month [ Time Frame: 12 month ]
    HIV related adverse events at 6 month will be determined according to CTC AE list version 4

  3. Prevalence of HIV Drug resistance mutations [ Time Frame: study start ]
    The prevalence of HIV drug resistance mutations will be determined in patients with virological failure of first-line antiretroviral therapy

  4. Pattern of HIV Drug resistance mutations [ Time Frame: study start ]
    The patterns of HIV drug resistance mutations will be determined in patients with virological failure of first-line antiretroviral therapy

  5. Viral load at 3th month [ Time Frame: 3 month ]
    Viral load will be measured by plasma HIV viral load measurement (copies per ml) after enhanced conselling.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   1 Month to 99 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Confirmed HIV positive patients on first-line ART
  2. Virological treatment failure with > 1000 copies/ ml

Exclusion Criteria:

  1. No consent given
  2. HIV patients with psychiatric disorders

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): NCT03557021


Contacts
Layout table for location contacts
Contact: Christa Kasang, PhD +4993180485 ext 18 christa.kasang@medmissio.de
Contact: Daniel Magesa, MD +255754307750 djnmagesa@yahoo.com

Locations
Layout table for location information
Tanzania
PASADA Recruiting
Dar es Salaam, Tanzania
Contact: Daniel Magesa, MD    +255754307750    djnmagesa@yahoo.com   
Baylor Hospital Not yet recruiting
Mwanza, Tanzania
Contact: Mercy Minde, MD       mminde@baylortanzania.or.tz   
Bugando Medical Center Recruiting
Mwanza, Tanzania
Contact: Henerico Shimba, MSc    +255657938070    henricus20@ymail.com   
Sponsors and Collaborators
Medical Mission Institute, Germany
National Institute for Medical Research, Tanzania
Investigators
Layout table for investigator information
Study Chair: John Changalucha, MD National Institute of Medical research Mwanza
Layout table for additonal information
Responsible Party: Dr. Christa Kasang, Research Coordinator, Medical Mission Institute, Germany
ClinicalTrials.gov Identifier: NCT03557021    
Other Study ID Numbers: HIVDR2
First Posted: June 14, 2018    Key Record Dates
Last Update Posted: June 14, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No