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

ANRS, Emerging Infectious Diseases

Status and phase: Completed; Phase 3

Conditions: HIV-1 Infection

Treatments: Drug: Efavirenz 400 mg; Drug: Dolutegravir 50 mg; Drug: Tenofovir disoproxil fumarate 300 mg / lamivudine 300 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT02777229

ANRS 12313 NAMSAL

Details and patient eligibility

About

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.

Enrollment: 616 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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616 participants in 2 patient groups

Dolutegravir

Experimental group

Description:

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

Treatment:

Drug: Tenofovir disoproxil fumarate 300 mg / lamivudine 300 mg

Drug: Dolutegravir 50 mg

Efavirenz

Active Comparator group

Description:

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

Treatment:

Drug: Tenofovir disoproxil fumarate 300 mg / lamivudine 300 mg

Drug: Efavirenz 400 mg