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

NCT ID: NCT03557021

Last Updated: 2018-06-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 1250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-01
• Study Completion Date: 2020-09-30

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.

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.

Conditions

HIV Drug Resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

HIV Drug resistance testing

Intervention Type: DIAGNOSTIC_TEST

HIV Drug resistance testing by HIV pro DNA sanger sequencing

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.

Group Type: ACTIVE_COMPARATOR

HIV Drug resistance testing

Intervention Type: DIAGNOSTIC_TEST

HIV Drug resistance testing by HIV pro DNA sanger sequencing

Interventions

HIV Drug resistance testing

HIV Drug resistance testing by HIV pro DNA sanger sequencing

Intervention Type: DIAGNOSTIC_TEST

Eligibility 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

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute for Medical Research, Tanzania

OTHER_GOV

Sponsor Role: collaborator

Medical Mission Institute, Germany

OTHER

Sponsor Role: lead

Responsible Party

Dr. Christa Kasang

Research Coordinator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John Changalucha, MD

Role: STUDY_CHAIR

National Institute of Medical research Mwanza

Locations

PASADA

Dar es Salaam, , Tanzania

Site Status: RECRUITING

Baylor Hospital

Mwanza, , Tanzania

Site Status: NOT_YET_RECRUITING

Bugando Medical Center

Mwanza, , Tanzania

Site Status: RECRUITING

Countries

Tanzania

Central Contacts

Christa Kasang, PhD

Role: CONTACT

christa.kasang@medmissio.de

+4993180485 ext. 18

Daniel Magesa, MD

Role: CONTACT

djnmagesa@yahoo.com

+255754307750

Facility Contacts

Daniel Magesa, MD

Role: primary

djnmagesa@yahoo.com

+255754307750

Mercy Minde, MD

Role: primary

mminde@baylortanzania.or.tz

Henerico Shimba, MSc

Role: primary

henricus20@ymail.com

+255657938070

Other Identifiers

HIVDR2

Identifier Type: -

Identifier Source: org_study_id