Efficacy and Safety of a Dolutegravir-based Regimen for the Initial Management of HIV Infected Adults in Resource-limited Settings

NCT02777229 | Completed Phase 3 DMC

• 1 other identifier: ANRS 12313 NAMSAL
• Study Type: interventional
• Target: 616
• Locations: 1 country
• Sites: 3

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.

Conditions

HIV-1 Infection

Keywords

Dolutegravir; Efavirenz-low-dose

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with Viral Load (VL) <50 cp/mL

  Proportion of patients with Viral Load (VL) \<50 cp/mL at week 48 (FDA snapshot algorithm)

  week 48

Secondary Outcomes (34)

• Proportion of patients with Viral Load (VL) <50 cp/mL

  week 96

• Proportion of patients with Viral Load (VL) <50 cp/mL

  week 24

• Proportion of patients with Viral Load (VL) < 200 cp/mL

  week 24, week 48, week 96, week 144, week 192

• 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

Study Arms (2)

Dolutegravir

EXPERIMENTAL

Dolutegravir 50 mg Quaque die (QD) + tenofovir disoproxil fumarate/lamivudine 300 mg/ 300 mg Fixed Dose Combination (FDC) QD

Drug: Dolutegravir 50 mg; Drug: Tenofovir disoproxil fumarate 300 mg / lamivudine 300 mg

Efavirenz

ACTIVE COMPARATOR

Efavirenz 400 mg QD + tenofovir disoproxil fumarate/lamivudine 300 mg/ 300 mg FDC QD

Drug: Tenofovir disoproxil fumarate 300 mg / lamivudine 300 mg; Drug: Efavirenz 400 mg

Interventions

Dolutegravir 50 mg DRUG

1 tablet once a day

Also known as: DTG

Dolutegravir

Tenofovir disoproxil fumarate 300 mg / lamivudine 300 mg DRUG

Fixed dose combination, 1 tablet once a day

Also known as: TDF / 3TC

Dolutegravir; Efavirenz

Efavirenz 400 mg DRUG

1 tablets once a day

Also known as: EFV400

Efavirenz

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• Institut de Recherche pour le Developpement: collaborator
• UNITAID: collaborator

Study Sites (3)

Cité verte Hospital

Yaoundé, Cameroon

Location

Hopital Central

Yaoundé, Cameroon

Location

Military Hospital

Yaoundé, Cameroon

Location

Related Publications (5)

• Mpoudi-Etame M, Tovar Sanchez T, Bousmah MA, Omgba Bassega P, Olinga J, Mimbe E, Foalem M, Chiep C, Edimo S, Varloteaux M, Pelloquin R, Lamare N, Boyer S, Peeters M, Reynes J, Calmy A, Hill A, Delaporte E, Kouanfack C; New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-income countries (NAMSAL-ANRS-12313) study group. Durability of the Efficacy and Safety of Dolutegravir-Based and Low-Dose Efavirenz-Based Regimens for the Initial Treatment of Human Immunodeficiency Virus Type 1 Infection in Cameroon: Week 192 Data of the NAMSAL-ANRS-12313 Study. Open Forum Infect Dis. 2023 Nov 20;10(12):ofad582. doi: 10.1093/ofid/ofad582. eCollection 2023 Dec.

  PMID: 38156046 DERIVED

• Bousmah MA, Protopopescu C, Mpoudi-Etame M, Omgba Bassega P, Maradan G, Olinga J, Varloteaux M, Tovar-Sanchez T, Delaporte E, Kouanfack C, Boyer S; NAMSAL ANRS 12313 Study Group. Improvements in Patient-Reported Outcomes Following Initiation of Dolutegravir-Based or Low-Dose Efavirenz-Based First-Line Antiretroviral Therapy: A Four-Year Longitudinal Analysis in Cameroon (NAMSAL ANRS 12313 Trial). J Acquir Immune Defic Syndr. 2023 Nov 1;94(3):262-272. doi: 10.1097/QAI.0000000000003273.

  PMID: 37851566 DERIVED

• Bousmah MA, Nishimwe ML, Tovar-Sanchez T, Lantche Wandji M, Mpoudi-Etame M, Maradan G, Omgba Bassega P, Varloteaux M, Montoyo A, Kouanfack C, Delaporte E, Boyer S; New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-Income Countries (NAMSAL) ANRS 12313 Study Group. Cost-Utility Analysis of a Dolutegravir-Based Versus Low-Dose Efavirenz-Based Regimen for the Initial Treatment of HIV-Infected Patients in Cameroon (NAMSAL ANRS 12313 Trial). Pharmacoeconomics. 2021 Mar;39(3):331-343. doi: 10.1007/s40273-020-00987-3. Epub 2020 Dec 23.

  PMID: 33355914 DERIVED

• Calmy A, Tovar Sanchez T, Kouanfack C, Mpoudi-Etame M, Leroy S, Perrineau S, Lantche Wandji M, Tetsa Tata D, Omgba Bassega P, Abong Bwenda T, Varloteaux M, Tongo M, Mpoudi-Ngole E, Montoyo A, Mercier N, LeMoing V, Peeters M, Reynes J, Delaporte E; New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-Income Countries (NAMSAL) ANRS 12313 Study Group. Dolutegravir-based and low-dose efavirenz-based regimen for the initial treatment of HIV-1 infection (NAMSAL): week 96 results from a two-group, multicentre, randomised, open label, phase 3 non-inferiority trial in Cameroon. Lancet HIV. 2020 Oct;7(10):e677-e687. doi: 10.1016/S2352-3018(20)30238-1.

  PMID: 33010241 DERIVED

• NAMSAL ANRS 12313 Study Group; Kouanfack C, Mpoudi-Etame M, Omgba Bassega P, Eymard-Duvernay S, Leroy S, Boyer S, Peeters M, Calmy A, Delaporte E. Dolutegravir-Based or Low-Dose Efavirenz-Based Regimen for the Treatment of HIV-1. N Engl J Med. 2019 Aug 29;381(9):816-826. doi: 10.1056/NEJMoa1904340. Epub 2019 Jul 24.

  PMID: 31339676 DERIVED

MeSH Terms

Interventions

dolutegravir; Tenofovir; Lamivudine; efavirenz

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Officials

• Eric Delaporte, MD, PhD

  IRD, INSERM, University Montpellier

  PRINCIPAL INVESTIGATOR

• Charles Kouanfack, MD, PhD

  Central Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2016
• First Posted: May 19, 2016
• Study Start: July 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2021
• Last Updated: August 31, 2021

Record last verified: 2021-02

Locations

CA (3)