MOPEB231

Title

Dolutegravir (DTG) plus lamivudine (3TC) versus DTG plus tenofovir/emtricitabine (TDF/FTC) fixed-dose combination in the GEMINI studies - viral load rebound including 'blips' through 48 weeks

Presenter

Mark Underwood

Authors

M. Underwood¹, R. Wang¹, J. Horton², C. Man¹, J. Sievers³, R. Urbaityte⁴, B. Wynne¹, A.-R. Tenorio¹, K. Pappa¹, J. Koteff¹, M. Gartland¹, M. Aboud³

Institutions

¹ViiV Healthcare, Research Triangle Park, United States, ²PAREXEL, Durham, United States, ³ViiV Healthcare, Brentford, United Kingdom, ⁴GlaxoSmithKline, Stockley Park, United Kingdom

Background: GEMINI-1 and GEMINI-2 are identical double-blind, multicentre, randomized, phase III, non-inferiority studies comparing dolutegravir+lamivudine (DTG+3TC) two-drug regimen (2DR) with DTG+ tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) three-drug regimen (3DR) once daily in HIV-1-infected ART-naïve adults, with screening HIV-1 RNA viral load (VL)< 500,000 c/mL. DTG+3TC was non-inferior to DTG+TDF/FTC through 48 Weeks, with respectively 91% (655/716) versus 93% (669/717) achieving VL< 50 c/mL using FDA snapshot algorithm. We assessed VL rebound through 48 weeks of therapy.
Methods: VL rebound after suppression to < 50 c/mL was assessed in two major participant categories (see TABLE): (1) with only VL ≥50 and < 200 c/mL, or (2) at least one VL≥200 c/mL after Day 1 (Baseline), and also (3) never suppressed to < 50 c/mL. Blips were defined as VL ≥50 and < 200 c/mL bounded by VL< 50 c/mL. Confirmed Virologic Withdrawal (CVW) criterion for resistance testing was: VL decrease < 1 log10 c/mL by Week 12, with subsequent confirmation, unless VL < 200 c/mL; or confirmed VL≥200 c/mL on or after Week 24; or confirmed VL≥200 c/mL after prior confirmed VL< 200 c/mL.
Results: 1433 participants were randomized and exposed (DTG+3TC, 716; DTG+TDF/FTC, 717) across both studies. At Week 48 six participants in the DTG+3TC group (0.8%) and four in the DTG+TDF/FTC group (0.6%) met CVW criteria; no participants in either arm meeting CVW had blips. No participants had treatment emergent resistance. Elevated VLs (Table) were comparable across arms; most participant VL rebounds occurred in Category 1, and most occurrences as defined blips.

	DTG + 3TC (N=716)	DTG+TDF/FTC (N=717)
1. Subjects with VLs between 50-200 c/mL and no viral load ≥200 c/mL after suppression to <50 c/mL	98 (14%)	101 (14%)
1a. VLs between 50-200 c/mL with adjacent values <50 c/mL (“blips”)	83 (12%)	93 (13%)
1b. ≥ two consecutive VLs between 50-200 c/mL	15 (2%)	8 (1%)
2. Subjects with least one VL ≥200 c/mL after suppression to <50 c/mL	19 (3%)	22 (3%)
2a. a single VL ≥200 c/mL with adjacent viral loads <200 c/mL	14 (2%)	19 (3%)
2b. ≥ two consecutive VLs ≥200 c/mL (CVW)	5* (0.7%)	3** (0.4%)
3. Subject VL never <50c/mL (most had only Day 1 (Baseline) visits)	8 (1%)	7 (1%)
Total (all categories)	125	130
One CVW in DTG+3TC arm never achieved <50c/mL, thus is counted in category 3. *One CVW in DTG+TDF/FTC arm was confirmed after Wk48 at Wk 60, thus is counted in category 2a in this analysis.

[Subject Categories (both 1 and 2 were after suppression to <50 c/mL)]

Conclusions: The incidence of participants with blips through 48 weeks was similar between the DTG+3TC 2DR and DTG+TDF/FTC 3DR arms. Other categories for VL≥50 occurred infrequently in all groups. CVWs were not associated with VL blips. This is further evidence for the efficacy and potency of DTG+3TC for the treatment of HIV.