Last updated on April 2020

Tenofovir/Lamivudine/Dolutegravir Combination as Second Line ART: a Randomised Controlled Trial (ARTIST)


Brief description of study

The strategy to support virological suppression on second-line antiretroviral treatment (ART) includes the provision of ART that has a low pill burden, good tolerability, low toxicity, is easily monitored, has a high barrier to resistance and that is low cost. The fixed dose combination of tenofovir, lamivudine and dolutegravir offers significant advantage as a potential second-line regimen compared to the World Health Organization standard of care second-line regimen of zidovudine, lamivudine and dolutegravir, in terms of cost, tolerability and monitoring requirements.

The ARTIST study will be a randomised, open-label, active-controlled trial with 48 weeks of follow up, and will evaluate the viral load suppression achieved by participants taking the fixed dose combination of tenofovir, lamivudine and dolutegravir or zidovudine, lamivudine and dolutegravir as second-line therapy. There is evidence to suggest that even in the presence of resistance mutations to tenofovir and lamivudine (K65R or M184V/I), using this backbone with dolutegravir will provide an effective second-line regimen in patients who have failed a first line regimen that includes a tenofovir and lamivudine or emtricitabine backbone and a non-nucleoside reverse transcriptase inhibitor (NNRTI).

The trial will comprise two stages: the first will evaluate the viral suppression in 65 participants produced by the fixed dose combination of tenofovir, lamivudine and dolutegravir with a supplementary dose of dolutegravir for the first 14 days to mitigate the NNRTI effect in reducing dolutegravir concentrations when switching antiretrovirals. The study will progress to the second stage if this proves effective, and 130 participants will then be randomised to receive the fixed dose combination of tenofovir, lamivudine and dolutegravir (without a supplementary dose of dolutegravir) or the WHO standard of care second-line regimen of zidovudine, lamivudine and dolutegravir.

The primary endpoint is viral suppression (viral load<50 copies/mL) at 24 weeks.

A Pharmacokinetic sub-study will be conducted on 12 participants in stage 1 and in 12 patients in stage 2 who are randomised to the intervention arm, to assess the trough concentrations of dolutegravir and off-treatment concentrations of efavirenz at day 3, 7, 14, and 28. This is to evaluate the need for the lead in supplementary dose of dolutegravir.

Clinical Study Identifier: NCT03991013

Find a site near you

Start Over