Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT05312918
Other study ID # ANRS 12427 DoReaL
Secondary ID
Status Not yet recruiting
Phase
First received
Last updated
Start date May 2022
Est. completion date October 2024

Study information

Verified date March 2022
Source ANRS, Emerging Infectious Diseases
Contact Avelin AGHOKENG
Phone 04 67 41 59 58
Email avelin.aghokeng@ird.fr
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Main objective The main objective of the study is to assess the virological efficacy of a Dolutegravir-based first-line ART in use under real-life conditions in national programs in resource-limited settings in patients infected with HIV-1 and initially under a NNRTI-based first-line, and determine the impact of NRTI resistance on the success of the new strategy. Secondary objectives - Determine the level of virological suppression (HIV-1 RNA <200 copies/ml) at 6, 12 and 24 months after transition from an NNRTI first-line to a DTG first-line. - Determine the level of virological suppression at the WHO threshold (HIV-1 RNA <1000 copies/ml). - To determine the frequency of development of resistance and the profiles of mutations in patients with virological failure (HIV-1 RNA ≥200 copies/ml) and the potential impact on the 2nd line strategies combining DTG and currently recommended by the WHO. - To determine the impact of pre-transition resistance to NRTIs on the virological suppression under DTG first-line and on the development of resistance to integrase inhibitors. - Study pre-transition resistance acquired under DTG first-lines at the thresholds of 20% and 5% of the viral population, respectively using Sanger and Ultra-deep Sequencing (UDS) approaches. Identify program factors associated with virological failure and/or the development of drug resistance.


Description:

Antiretroviral therapy (ART) has dramatically changed the pronostic of HIV/AIDS infection over the last 20 years, by reducing the mortality and morbibidity associted with the infection. This is mostly true in sub-Saharan African, the most affected region of the world. The UNAIDS 2019 report confirms this fact, and shows a significant reduction in the number of deaths related to HIV infection as access to antiretrovirals (ARV) increases. However, in the absence of cure by current treatments, the management and treatment of the infection should still be considered for life. This makes this management complex and challenging. Indeed, the risk of failure to treatment is real, this risk is accompanied by that of developing resistance to treatment, which should lead to a change in treatment. The limited number of molecules therefore requires the development of strategies that must be effective in maintaining virological suppression for as long as possible and should also limit the emergence and circulation of resistant viruses. To address these priorities, the World Health Organization (WHO) recommends since 2016, the introduction of a first-line ART more efficient and more robust, combining molecules with a high genetic barrier to resistance. In its latest 2019 recommendations for resource-limited countries, WHO recommends a first-line ART comprising two nucleoside reverse transcriptase inhibitors (NRTIs) and one integrase inhibitor (INI), preferably tenofovir (TDF)+Lamivudine (3TC )/emtricitabine (FTC)+dolutegravir (DTG). This new strategy is expected in the context of sub-Saharan Africa, where the increase of pre-treatment and acquired HIV drug resistance has been worrying for several years, but raises a certain number of uncertainties. Indeed, available and published data on the effectiveness of DTG are mainly from studies conducted in Northern countries, very few clinical trials have evaluated or are underway to evaluate the strategy in Southern countries and virtually no evaluation of the effectiveness of this approach in the context of real life in the South has been conducted to date. In addition, few or no recommendations have been made to accompany this transition to a new DTG-based first-line in the South. This is of greater concern for patients who are currently under non-NRTI-based first-line , and who will be switched to a new DTG-based first-line. This population will certainly include very variable virological profiles, ranging from patients in virological suppression, to patients who are not virologically suppressed, with potential accumulation of resistance mutations. In the absence of clear and funded recommendations for the organization of these transitions, the risk of this transition producing results below expectations is real and significant. In addition, the reality of the management of HIV infection in the South regularly faces significant challenges associated with limited financial and human resources. This often makes it difficult to apply decisions made even at the national level. For illustration, despite the unanimity around the use of viral load for monitoring people on ART, access to and the availability of this test in daily practice remains challenging in many countries. It is therefore essential to evaluate the virological response in people who will be switched from the current first-line, to the new first-line, in real life conditions, in the South. This study, developed and considered as a priority by the AC43 working group "Medical Virology" of the ANRS, aims to evaluate this new strategy in real life context in three countries of sub-Saharan Africa, Côte d'Ivoire, Mali and Togo. The main objective is to assess the virological efficacy of the DTG-based first-line in real life conditions, for patients initially receiving an NNRTI-based first-line, followed-up in the national programs and determine the impact of baseline NRTI-drug resistance on the success of the new strategy. All these three countries have adopted the new WHO recommendations and the deployment of the DTG-based first-line is being initiated. It is therefore essential that this research be conducted along side with this ongoing transition, so that the results will help developping adequate recommendations that will allow programs in the South to better organise the transition, to improve the therapeutic and virological monitoring of patients, to prevent early failures, and the emergence and rapid circulation of drug resistance.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 603
Est. completion date October 2024
Est. primary completion date March 2023
Accepts healthy volunteers
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Aged 18 years or over. - Infected with HIV-1. - On an NNRTI-based first-line for at least 6 months. - Initiating a new 1st line ART based on DTG according to national recommendations. - Agree to participate in the study and provide free, written and informed consent. Exclusion Criteria: - Infection with HIV-2 or HIV1+2. - Ongoing participation in another virological study on HIV infection

Study Design


Related Conditions & MeSH terms


Locations

Country Name City State
Côte D'Ivoire CIRBA Abidjan
Mali SEREFO Bamako
Togo Biolim/Fss/Ul Lomé

Sponsors (4)

Lead Sponsor Collaborator
ANRS, Emerging Infectious Diseases BIOLIM/FSS/UL, Lomé, Togo, CIRBA, Abidjan, Ivory Coast, SEREFO, Bamako, Mali

Countries where clinical trial is conducted

Côte D'Ivoire,  Mali,  Togo, 

Outcome

Type Measure Description Time frame Safety issue
Primary Proportion virological success Proportion of patients with virological success at Week 48 (Month 12), defined by a VL <200 copies/ml. 48 weeks
Secondary Virological suppression at W24 (VL< 200 copies/ml) Proportion of patients with virological suppression at W24 (VL< 200 copies/ml). 24 weeks
Secondary Virological suppression at W96 (VL< 200 copies/ml) Proportion of patients with virological suppression at W96 (VL< 200 copies/ml). 96 weeks
Secondary Virological suppression at VL thresholds of 200 copies/ml, considering the first point of viral load and the control viral load if the first point of viral load was >200 copies/ml. Proportion of patients with virological suppression at VL thresholds of 200 copies/ml, considering the first point of viral load at W24 and the control viral load at W36 if the first point of viral load was >200 copies/ml. 36 weeks
Secondary Virological suppression at VL thresholds of 200 copies/ml, considering the first point of viral load and the control viral load if the first point of viral load was >200 copies/ml. Proportion of patients with virological suppression at VL thresholds of 200 copies/ml, considering the first point of viral load at W48, and the control viral load at W60 if the first point of viral load was >200 copies/ml. 60 weeks
Secondary Virological suppression at VL thresholds of 200 copies/ml, considering the first point of viral load and the control viral load if the first point of viral load was >200 copies/ml. Proportion of patients with virological suppression at VL thresholds of 200 copies/ml, considering the first point of viral load at W96, and the control viral load at W108 if the first point of viral load was >200 copies/ml. 108 weeks
Secondary Virological suppression at the WHO threshold (< 1000 copies/ml). Proportion of patients with virological suppression at the WHO threshold at W24 (< 1000 copies/ml). 24 weeks
Secondary Virological suppression at the WHO threshold (< 1000 copies/ml). Proportion of patients with virological suppression at the WHO threshold at W48 (< 1000 copies/ml). 48 weeks
Secondary Virological suppression at the WHO threshold (< 1000 copies/ml). Proportion of patients with virological suppression at the WHO threshold at W96 (< 1000 copies/ml). 96 weeks
Secondary Virological suppression at VL thresholds of 1000 copies/ml, considering the first point of viral load, and the control viral load if the first point of viral load was >1000 copies/ml. Proportion of patients with virological suppression at VL thresholds of 1000 copies/ml, considering the first point of viral load at W24, and the control viral load at W36 if the first point of viral load was >1000 copies/ml. 36 weeks
Secondary Virological suppression at VL thresholds of 1000 copies/ml, considering the first point of viral load, and the control viral load if the first point of viral load was >1000 copies/ml. Proportion of patients with virological suppression at VL thresholds of 1000 copies/ml, considering the first point of viral load at W48, and the control viral load at W60 if the first point of viral load was >1000 copies/ml. 60 weeks
Secondary Virological suppression at VL thresholds of 1000 copies/ml, considering the first point of viral load, and the control viral load if the first point of viral load was >1000 copies/ml. Proportion of patients with virological suppression at VL thresholds of 1000 copies/ml, considering the first point of viral load at W96, and the control viral load at W108 if the first point of viral load was >1000 copies/ml. 108 weeks
Secondary Virological suppression at the optimal threshold (<50 copies/ml) Proportion of patients with virological suppression at the optimal threshold at W24 (<50 copies/ml) 24 weeks
Secondary Virological suppression at the optimal threshold (<50 copies/ml) Proportion of patients with virological suppression at the optimal threshold at W48 (<50 copies/ml) 48 weeks
Secondary Virological suppression at the optimal threshold (<50 copies/ml) Proportion of patients with virological suppression at the optimal threshold at W96 (<50 copies/ml) 96 weeks
Secondary Virological suppression at VL thresholds of 50 copies/ml, considering the first point of viral load, and the control viral load if the first point of viral load was >50 copies/ml. Proportion of patients with virological suppression at VL thresholds of 50 copies/ml, considering the first point of viral load at W24, and the control viral load at W36 if the first point of viral load was >50 copies/ml. 36 weeks
Secondary Virological suppression at VL thresholds of 50 copies/ml, considering the first point of viral load, and the control viral load if the first point of viral load was >50 copies/ml. Proportion of patients with virological suppression at VL thresholds of 50 copies/ml, considering the first point of viral load at W48, and the control viral load at W60 if the first point of viral load was >50 copies/ml. 60 weeks
Secondary Virological suppression at VL thresholds of 50 copies/ml, considering the first point of viral load, and the control viral load if the first point of viral load was >50 copies/ml. Proportion of patients with virological suppression at VL thresholds of 50 copies/ml, considering the first point of viral load at W96, and the control viral load at W108 if the first point of viral load was >50 copies/ml. 108 weeks
Secondary Proportion of patients with virological suppression at VL thresholds of 50, 200 copies/ml and 1000 copies/ml, depending on the viral load at the time of switch Proportion of patients with virological suppression at VL thresholds of 50, 200 copies/ml and 1000 copies/ml, at W24, depending on the viral load at the time of switch according to 3 groups (VL of D0 <200 copies/ml, between 200 and 1000 copies/ml, and =1000 copies/ml) 24 weeks
Secondary Proportion of patients with virological suppression at VL thresholds of 50, 200 copies/ml and 1000 copies/ml, depending on the viral load at the time of switch Proportion of patients with virological suppression at VL thresholds of 50, 200 copies/ml and 1000 copies/ml, at W48, depending on the viral load at the time of switch according to 3 groups (VL of D0 <200 copies/ml, between 200 and 1000 copies/ml, and =1000 copies/ml) 48 weeks
Secondary Proportion of patients with virological suppression at VL thresholds of 50, 200 copies/ml and 1000 copies/ml, depending on the viral load at the time of switch Proportion of patients with virological suppression at VL thresholds of 50, 200 copies/ml and 1000 copies/ml, at W96, depending on the viral load at the time of switch according to 3 groups (VL of D0 <200 copies/ml, between 200 and 1000 copies/ml, and =1000 copies/ml) 96 weeks
Secondary Frequency of drug resistance Frequency of resistance mutations acquired at confirmed virological failure, at VL thresholds of 200 copies/ml and 1000 copies/ml. 24 weeks
Secondary Profiles of resistance mutations Profiles of resistance mutations acquired at confirmed virological failure, at VL thresholds of 200 copies/ml and 1000 copies/ml. 24 weeks
Secondary Frequency of drug resistance Frequency of resistance mutations acquired at confirmed virological failure, at VL thresholds of 200 copies/ml and 1000 copies/ml. 48 weeks
Secondary Profiles of resistance mutations Profiles of resistance mutations acquired at confirmed virological failure, at VL thresholds of 200 copies/ml and 1000 copies/ml. 48 weeks
Secondary Frequency of drug resistance Frequency of resistance mutations acquired at confirmed virological failure, at VL thresholds of 200 copies/ml and 1000 copies/ml. 96 weeks
Secondary Profiles of resistance mutations Profiles of resistance mutations acquired at confirmed virological failure, at VL thresholds of 200 copies/ml and 1000 copies/ml. 96 weeks
Secondary GSS (Genotypic susceptibility score) Proportion of patients with a GSS =1 at W24 24 weeks
Secondary GSS (Genotypic susceptibility score) Proportion of patients with a GSS =1 at W48 48 weeks
Secondary GSS (Genotypic susceptibility score) Proportion of patients with a GSS =1 at W96. 96 weeks
Secondary Frequency of pre-transition resistance mutations to NRTIs Frequency of pre-transition resistance mutations to NRTIs At baseline, before DTG initiation
Secondary Proportion of HIV minority variants Proportion of minority variants (5% threshold) in patients with resistance mutations to NRTIs and/or DTG in the event of virological failure. Up to 108 weeks.
See also
  Status Clinical Trial Phase
Completed NCT05454514 - Automated Medication Platform With Video Observation and Facial Recognition to Improve Adherence to Antiretroviral Therapy in Patients With HIV/AIDS N/A
Completed NCT03760458 - The Pharmacokinetics, Safety, and Tolerability of Abacavir/Dolutegravir/Lamivudine Dispersible and Immediate Release Tablets in HIV-1-Infected Children Less Than 12 Years of Age Phase 1/Phase 2
Completed NCT03141918 - Effect of Supplementation of Bioactive Compounds on the Energy Metabolism of People Living With HIV / AIDS N/A
Completed NCT03067285 - A Phase IV, Open-label, Randomised, Pilot Clinical Trial Designed to Evaluate the Potential Neurotoxicity of Dolutegravir/Lamivudine/Abacavir in Neurosymptomatic HIV Patients and Its Reversibility After Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide. DREAM Study Phase 4
Recruiting NCT04579146 - Coronary Artery Disease (CAD) in Patients HIV-infected
Completed NCT06212531 - Papuan Indigenous Model of Male Circumcision N/A
Active, not recruiting NCT03256422 - Antiretroviral Treatment Taken 4 Days Per Week Versus Continuous Therapy 7/7 Days Per Week in HIV-1 Infected Patients Phase 3
Completed NCT03256435 - Retention in PrEP Care for African American MSM in Mississippi N/A
Completed NCT00517803 - Micronutrient Supplemented Probiotic Yogurt for HIV/AIDS and Other Immunodeficiencies N/A
Active, not recruiting NCT03572335 - Systems Biology of Diffusion Impairment in Human Immunodeficiency Virus (HIV)
Completed NCT04165200 - Fecal Microbiota Transplantation as a Therapeutic Strategy for Patients Infected With HIV N/A
Recruiting NCT03854630 - Hepatitis B Virus Vaccination in HIV-positive Patients and Individuals at High Risk for HIV Infection Phase 4
Terminated NCT03275571 - HIV, Computerized Depression Therapy & Cognition N/A
Completed NCT02234882 - Study on Pharmacokinetics Phase 1
Completed NCT01618305 - Evaluating the Response to Two Antiretroviral Medication Regimens in HIV-Infected Pregnant Women, Who Begin Antiretroviral Therapy Between 20 and 36 Weeks of Pregnancy, for the Prevention of Mother-to-Child Transmission Phase 4
Recruiting NCT05043129 - Safety and Immune Response of COVID-19 Vaccination in Patients With HIV Infection
Not yet recruiting NCT05536466 - The Influence of Having Bariatric Surgery on the Pharmacokinetics, Safety and Efficacy of the Novel Non-nucleoside Reverse Transcriptase Inhibitor Doravirine N/A
Recruiting NCT04985760 - Evaluation of Trimer 4571 Therapeutic Vaccination in Adults Living With HIV on Suppressive Antiretroviral Therapy Phase 1
Completed NCT05916989 - Stimulant Use and Methylation in HIV
Terminated NCT02116660 - Evaluation of Renal Function, Efficacy, and Safety When Switching From Tenofovir/Emtricitabine Plus a Protease Inhibitor/Ritonavir, to a Combination of Raltegravir (MK-0518) Plus Nevirapine Plus Lamivudine in HIV-1 Participants With Suppressed Viremia and Impaired Renal Function (MK-0518-284) Phase 2