A Phase III Randomized, Open Label Trial to Evaluate Dolutegravir Versus Efavirenz 400 mg, Both Combined With Tenofovir Disoproxil Fumarate + Lamivudine for the Initial Management of HIV Infected Adults in Resource-limited Settings
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 616
- Locations
- 3
- Primary Endpoint
- Proportion of patients with Viral Load (VL) <50 cp/mL
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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.
Arms & Interventions
Dolutegravir
Dolutegravir 50 mg Quaque die (QD) + tenofovir disoproxil fumarate/lamivudine 300 mg/ 300 mg Fixed Dose Combination (FDC) QD
Intervention: Dolutegravir 50 mg (Drug)
Dolutegravir
Dolutegravir 50 mg Quaque die (QD) + tenofovir disoproxil fumarate/lamivudine 300 mg/ 300 mg Fixed Dose Combination (FDC) QD
Intervention: Tenofovir disoproxil fumarate 300 mg / lamivudine 300 mg (Drug)
Efavirenz
Efavirenz 400 mg QD + tenofovir disoproxil fumarate/lamivudine 300 mg/ 300 mg FDC QD
Intervention: Tenofovir disoproxil fumarate 300 mg / lamivudine 300 mg (Drug)
Efavirenz
Efavirenz 400 mg QD + tenofovir disoproxil fumarate/lamivudine 300 mg/ 300 mg FDC QD
Intervention: Efavirenz 400 mg (Drug)
Outcomes
Primary Outcomes
Proportion of patients with Viral Load (VL) <50 cp/mL
Time Frame: week 48
Proportion of patients with Viral Load (VL) \<50 cp/mL at week 48 (FDA snapshot algorithm)
Secondary Outcomes
- Time to virologic failure(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(Baseline, week 48, week 96, week 144, week 192)
- Time to death or to disease progression(week 48, week 96, week 144, week 192)
- Changes in Alanine Aminotransferase (ALT) from baseline to endpoints week-48, -96, -144, -192(Baseline, week 48, week 96, week 144, week 192)
- Incidence of first grade 3 or 4 clinical adverse event(week 48, week 96, week 144, week 192)
- Proportion of patients with Viral Load (VL) < 200 cp/mL(week 24, week 48, week 96, week 144, week 192)
- Hemoglobine changes 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(Baseline, week 48, week 96, week 144, week 192)
- Proportion of patients with Viral Load (VL) <50 cp/mL(week 24)
- AE and SAE(week 48, week 96, week 144, week 192)
- 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 level of HDL from baseline to endpoints week-48, -96, -144, -192(Baseline, week 48, week 96, week 144, week 192)
- Time to first toxicity failure(week 48, week 96, week 144, week 192)
- Time to treatment discontinuation(week 48, week 96, week 144, week 192)
- Changes in creatinine from baseline to endpoints week-48, -96, -144, -192(Baseline, week 48, week 96, week 144, week 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 level of total cholesterol 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(Baseline, week 48, week 96, week 144, week 192)
- Incidence of first grade 3 or 4 laboratory adverse event(week 48, week 96, week 144, week 192)
- Changes in level of triglycerides from baseline to endpoints week-48, -96, -144, -192(Baseline, week 48, week 96, week 144, week 192)
- Proportion of patients defaulting clinic schedule(week 48, week 96, week 144, week 192)
- Mean medication adherence level from baseline to endpoints week-48, -96, -144, -192(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(Baseline, week 48, week 96, week 144, week 192)
- HbA1c(week 192)
- Mean change in EFV-related symptoms questionnaire score from baseline to endpoints week-48, -96, -144, -192(Baseline, week 48, week 96)
- Levels of adiponectin(Baseline, week 48, week 96, week 144, week 192)
- Levels of ghrelin(Baseline, week 48, week 96, week 144, week 192)
- Tobacco status consumtion(week 192)
- Lipodistrophia(week 192)
- Levels of leptin(Baseline, week 48, week 96, week 144, week 192)
- hsPCR(week 192)
- PWV(week 192)
- CIMT(week 192)