Primary Efficacy Outcome | |
Difference in proportion with clinical or virological failure by 96 weeks, defined as the first occurrence of any of the following components: 1. Insufficient virological response defined as <1 log10 drop at week 24 (or viral load ≥50c/mL at week 24 in a participant with viral load < 500c/mL at baseline) and switch to second/third line antiretroviral therapy for treatment failure 2. Virological failure (defined as a viral load of greater than or equal to 400 copies/mL at or after week 36 confirmed by the next visit) 3. New or recurrent AIDS defining event (WHO 4) or severe WHO 3 event, confirmed by the Endpoint Review Committee (see Appendix) 4. All-cause death | |
Secondary efficacy outcomes | |
Difference in proportion with clinical or virological failure (as defined above) by 48 weeks | |
Time to any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events, confirmed by the Endpoint Review Committee | |
Proportion of children with Viral Load < 50 c/ml at 48 and 96 weeks | |
Proportion of children with Viral Load < 400 c/ml at 48 and 96 weeks | |
Rate of HIV-associated events (WHO 4 and severe WHO 3) and death over 96 weeks | |
Change in CD4 count and percentage and CD4/CD8 ratio from baseline to weeks 48 and 96 | |
Proportion developing new resistance mutations | |
Secondary safety outcomes | |
Change in total cholesterol, triglycerides and lipid fractions (high-density lipoproteins, low-density lipoproteins) from baseline to weeks 48 and 96 (change in total cholesterol from baseline to week 96 will be used to formally assess superiority of dolutegravir-based regimen vs. standard-of-care) | |
Incidence of serious adverse events | |
Incidence of new clinical and laboratory grade 3 and 4 adverse events | |
Incidence of adverse events (of any grade) leading to treatment modification | |
Other secondary outcomes | |
Quality of life | |
Adherence and acceptability |