Efficacy and Safety of a Dolutegravir-based Regimen for the Initial Management of HIV Infected Adults in Resource-limited Settings
- Conditions
- HIV-1 Infection
- Interventions
- Registration Number
- NCT02777229
- Lead Sponsor
- ANRS, Emerging Infectious Diseases
- Brief Summary
Several reports indicate that treatment failure due to HIV resistance or to adverse event-related discontinuation could compromise the effectiveness of scaling-up antiretroviral treatment (ART), especially when lack of access to viral load is a concern. Combined with other nucleoside reverse transcriptase inhibitor, Dolutegravir (DTG) is a very promising alternative to the current first-line non nucleoside reverse transcriptase inhibitor-based regimens.
Initial evaluations of DTG conducted in high income countries showed excellent efficacy and safety and indicated high genetic barrier thus preserving second line treatment. As a consequence, DTG-based regimens have been recently included in the first-line options in the national guidelines for ART of several high-income countries. However, the clinical trials evaluating DTG-based regimens have been conducted in highly controlled conditions, including baseline resistance testing and regular viral load monitoring. Moreover, these trials included a high proportion of men with rare co-morbidities.
There is need to evaluate how a DTG-based regimen will perform in real-world conditions within resources-constrained settings, where viral load monitoring is limited, and where the majority of HIV patients are women with important family planning consideration and NAMSAL trial is a randomized clinical trial which aims to evaluate efficacy and safety over 48, 96 and 192 weeks of DTG + tenofovir disoproxil fumarate/lamivudine versus Efavirenz (EFV) + tenofovir disoproxil fumarate/lamivudine in 606 ART-naïve HIV-1-infected adults in Cameroon. A set of efficacy and safety endpoints will be compared over 48, 96 and 192 weeks between the two arms including the proportion of patients with viral load \<50 copies/mL and incidence of severe adverse events.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 616
- HIV-1 infected
- Age ≥ 18 years
- Abtiretroviral-naïve, including above 7 days of cumulative prior antiretroviral therapy at any time prior to study entry.
- For women of childbearing potential: acceptance to use effective contraceptive methods
- Provision of written informed consent
- Infection with HIV-1 group O, N, P
- Infection or co-infection with HIV-2
- Absolute neutrophil count (ANC) < 500 cells/mm3
- Hemoglobin < 7.0 g/dL
- Platelet count < 50,000 cells/mm3
- AST and/or ALT > 5 x Upper Limit of Normal (ULN)
- Calculated creatinine clearance < 50 mL/min
- Active opportunistic or severe disease not under adequate control
- For women of childbearing age : Pregnancy/breastfeeding
- History or presence of allergy and/or contraindications to the trial drugs or their components
- Severe psychiatric illness
- Severe hepatic failure Patients co-infected with tuberculosis (TB), receiving a TB treatment and with stable clinical condition will not be excluded.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dolutegravir Dolutegravir 50 mg Dolutegravir 50 mg Quaque die (QD) + tenofovir disoproxil fumarate/lamivudine 300 mg/ 300 mg Fixed Dose Combination (FDC) QD Efavirenz Efavirenz 400 mg Efavirenz 400 mg QD + tenofovir disoproxil fumarate/lamivudine 300 mg/ 300 mg FDC QD Dolutegravir Tenofovir disoproxil fumarate 300 mg / lamivudine 300 mg Dolutegravir 50 mg Quaque die (QD) + tenofovir disoproxil fumarate/lamivudine 300 mg/ 300 mg Fixed Dose Combination (FDC) QD Efavirenz Tenofovir disoproxil fumarate 300 mg / lamivudine 300 mg Efavirenz 400 mg QD + tenofovir disoproxil fumarate/lamivudine 300 mg/ 300 mg FDC QD
- Primary Outcome Measures
Name Time Method Proportion of patients with Viral Load (VL) <50 cp/mL week 48 Proportion of patients with Viral Load (VL) \<50 cp/mL at week 48 (FDA snapshot algorithm)
- Secondary Outcome Measures
Name Time Method Time to virologic failure week 48, week 96, week 144, week 192 Time to virologic failure
Changes in Cluster of differentiation 4 (CD4)-cell count from baseline to endpoints week-48, -96, -144, -192 Baseline, week 48, week 96, week 144, week 192 Changes in Cluster of differentiation 4 (CD4)-cell count from baseline to endpoints week-48, -96, -144, -192
Time to death or to disease progression week 48, week 96, week 144, week 192 Time to death or to disease progression
Changes in Alanine Aminotransferase (ALT) from baseline to endpoints week-48, -96, -144, -192 Baseline, week 48, week 96, week 144, week 192 Changes in Alanine Aminotransferase (ALT) from baseline to endpoints week-48, -96, -144, -192
Incidence of first grade 3 or 4 clinical adverse event week 48, week 96, week 144, week 192 Incidence of first grade 3 or 4 clinical adverse event
Proportion of patients with Viral Load (VL) < 200 cp/mL week 24, week 48, week 96, week 144, week 192 Proportion of patients with VL\< 200 cp/mL (FDA snapshot algorithm)
Hemoglobine changes from baseline to endpoints week-48, -96, -144, -192 Baseline, week 48, week 96, week 144, week 192 Changes in hemoglobin Time to virologic failure from baseline to endpoints week-48, -96, -144, -192
Changes in level of fasting glucose from baseline to endpoints week-48, -96, -144, -192 Baseline, week 48, week 96, week 144, week 192 Changes in level of fasting glucose from baseline to endpoints week-48, -96, -144, -192
Proportion of patients with Viral Load (VL) <50 cp/mL week 24 Proportion of patients with VL\< 50 cp/mL at week 24 (FDA snapshot algorithm)
AE and SAE week 48, week 96, week 144, week 192 Incidence of adverse events (AE) and serious adverse event (SAE)
Changes in estimated glomerular filtration rate from baseline to endpoints week-48, -96, -144, -192 Baseline, week 48, week 96, week 144, week 192 Changes in estimated glomerular filtration rate from baseline to endpoints week-48, -96, -144, -192
Changes in level of HDL from baseline to endpoints week-48, -96, -144, -192 Baseline, week 48, week 96, week 144, week 192 Changes in level of HDL from baseline to endpoints week-48, -96, -144, -192
Time to first toxicity failure week 48, week 96, week 144, week 192 Time to first toxicity failure
Time to treatment discontinuation week 48, week 96, week 144, week 192 Time to treatment discontinuation
Changes in creatinine from baseline to endpoints week-48, -96, -144, -192 Baseline, week 48, week 96, week 144, week 192 Changes in creatinine from baseline to endpoints week-48, -96, -144, -192
Changes in Aspartate Aminotransferase (AST) ffrom baseline to endpoints week-48, -96, -144, -192 Baseline, week 48, week 96, week 144, week 192 Changes in Aspartate Aminotransferase (AST) from baseline to endpoints week-48, -96, -144, -192
Changes in level of total cholesterol from baseline to endpoints week-48, -96, -144, -192 Baseline, week 48, week 96, week 144, week 192 Changes in level of total cholesterol from baseline to endpoints week-48, -96, -144, -192
Mean change in Depression Anxiety Stress Scale from baseline to endpoints week-48, -96, -144, -192 Baseline, week 48, week 96, week 144, week 192 Mean change in Depression Anxiety Stress Scale from baseline to endpoints week-48, -96, -144, -192
* Depression Normal 0-9, Mild 10-13, Moderate 14-20, Severe 21-27, Extremely Severe +28
* Anxiety Normal 0-7, Mild 8-9, Moderate 10-14, Severe 15-19, Extremely Severe +20
* Stress Normal 0-14, Mild 15-18, Moderate 19-25, Severe 26-33, Extremely Severe +34Incidence of first grade 3 or 4 laboratory adverse event week 48, week 96, week 144, week 192 Incidence of first grade 3 or 4 laboratory adverse event
Changes in level of triglycerides from baseline to endpoints week-48, -96, -144, -192 Baseline, week 48, week 96, week 144, week 192 Changes in level of triglycerides from baseline to endpoints week-48, -96, -144, -192
Proportion of patients defaulting clinic schedule week 48, week 96, week 144, week 192 Proportion of patients defaulting clinic schedule
Mean change in Quality of life score assessed by the Short Form health survey from baseline to endpoints week-48, -96, -144, -192 Baseline, week 48, week 96, week 144, week 192 Mean change in Quality of life score assessed by the Short Form health survey from baseline to endpoints week-48, -96, -144, -192 (Score varies according to the items, in order to test the vigilance of the patient. Reading the results provides a semantic appreciation)
HbA1c week 192 Levels of glycated hemoglobin
Mean medication adherence level from baseline to endpoints week-48, -96, -144, -192 week 48, week 96, week 144, week 192 Mean medication adherence level from baseline to endpoints week-48, -96, -144, -192
Mean change in EFV-related symptoms questionnaire score from baseline to endpoints week-48, -96, -144, -192 Baseline, week 48, week 96 Mean change in EFV-related symptoms questionnaire score from baseline to endpoints week-48, -96, -144, -192
Levels of adiponectin Baseline, week 48, week 96, week 144, week 192 Levels of adiponectin
Levels of ghrelin Baseline, week 48, week 96, week 144, week 192 Levels of ghrelin
Tobacco status consumtion week 192 The status of tobacco smoker / non-smoker will be requested.
Lipodistrophia week 192 Qualitative and quantitative measurements of soft tissue composition = Lipodistrophia
Levels of leptin Baseline, week 48, week 96, week 144, week 192 Levels of leptin
hsPCR week 192 Levels of high sensitivity protein C reactive
CIMT week 192 Mesures of Carotid Intima-Media Thickness
PWV week 192 Mesures of Pulse Wave Velocity
Trial Locations
- Locations (3)
Military Hospital
🇨🇲Yaoundé, Cameroon
Hopital Central
🇨🇲Yaoundé, Cameroon
Cité verte Hospital
🇨🇲Yaoundé, Cameroon