The primary purpose of this study is to see if people with HIV who had a significant weight gain after starting INSTI (integrase strand transfer inhibitor)+TAF/FTC (tenofovir alafenamide/emtricitabine) (TAF/3TC (lamivudine)) regimen could either slow their rate of weight gain or lose weight within about 1 year if they switch to a regimen containing doravirine (DOR; a newer, non-nucleoside reverse transcriptase inhibitor medication). The study will also try to see if participants changing from TAF/FTC (or TAF/3TC) to TDF/FTC (or TDF/3TC) will experience less additional weight gain or a reduction in overall body weight at 48 weeks compared to persons continued on an INSTI + TAF/FTC (or TAF/3TC) combination. INSTINs assessed in A5391 include bictegravir (BIC), dolutegravir (DTG), or raltegravir (RAL). Additionally, the study will see whether a change in ART can affect things like waist circumference, metabolic and cardiovascular health, fat and lean mass body composition, bone health, and maintenance of virologic suppression. Finally, the study will look at the safety and tolerability of DOR plus either TAF/FTC (or TAF/3TC) versus TDF/FTC (or TDF/3TC).
Name: Doravirine 100 Mg
Name: Tenofovir alafenamide/emtricitabine
Name: tenofovir alafenamide/lamivudine
Name: Integrase strand transfer inhibitors
Name: tenofovir disproxil fumarate/emtricitabine
Name: tenofovir disproxil fumarate/lamivudine
Description: Proportion of participants with confirmed plasma HIV-1 RNA >200 copies/mL
Measure: Occurrence of confirmed plasma HIV-1 RNA >200 copies/mL Time: At day 0, weeks 4, 12, 24, and 48Description: Proportion of participants with Grade ≥3 AEs or >10% reduction in CrCl as estimated by the CKD-EPI equation
Measure: Occurrence of Grade ≥3 AEs or >10% reduction in CrCl as estimated by the CKD-EPI equation Time: Day 0 to week 48Description: Proportion of participants who prematurely discontinued study treatment
Measure: Occurrence of premature discontinuation of study treatment Time: Day 0 to week 48Allocation: Randomized
Parallel Assignment
There are 2 SNPs
- Aspartate aminotransferase (AST) (SGOT) <3x ULN - Alanine aminotransferase (ALT) (SGPT) <3x ULN Exclusion Criteria: - Historical or current evidence of the K65R/E/N or M184V/I mutations (for participants who have undergone HIV-1 genotyping), due to the potential for viral rebound after switch from an INSTI- to NNRTI-based regimen. --- K65R ---
- Aspartate aminotransferase (AST) (SGOT) <3x ULN - Alanine aminotransferase (ALT) (SGPT) <3x ULN Exclusion Criteria: - Historical or current evidence of the K65R/E/N or M184V/I mutations (for participants who have undergone HIV-1 genotyping), due to the potential for viral rebound after switch from an INSTI- to NNRTI-based regimen. --- K65R --- --- M184V ---