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

• Status: Completed
• Trial end date: 2021-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ANRS, Emerging Infectious Diseases; French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Collaborators: Institut de Recherche pour le Developpement; UNITAID
• Treatments: Dolutegravir; Efavirenz; Lamivudine; Tenofovir

Criteria

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.