This trial evaluates options for second-line antiretroviral therapy in patients failing on a
non-nucleoside reverse transcriptase inhibitor (NNRTI) and tenofovir (TDF)-based first-line
regimen in the setting of the public health approach in sub-Saharan Africa (with assumed
substantial nucleoside reverse transcriptase inhibitor (NRTI) cross-resistance). The trial
tests two hypotheses. Firstly that a regimen of dolutegravir (DTG) with two NRTIs is
non-inferior to a regimen of ritonavir-boosted darunavir (DRV/r) with two NRTIs. Secondly
that continuing an NRTI regimen of TDF and lamivudine (3TC) is non-inferior to switching to
zidovudine (ZDV) and 3TC.
The trial is a parallel group, open-label, multi-centre, factorial (2X2) randomised,
controlled trial. Patients will be randomised to either DTG or DRV/r with a second
randomisation to ZDV and 3TC or TDF and 3TC. Treatment efficacy will be monitored by testing
viral load (VL). Analyses will compare DRV/r with DTG; and ZDV/3TC with TDF/3TC by intention
to treat analysis on the primary outcome parameter of plasma VL below 400 copies/ml at 48
weeks. Trial follow-up will continue to 96 weeks.