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Clinical Trial
. 2021 Jun 1;87(2):801-805.
doi: 10.1097/QAI.0000000000002642.

Brief Report: Switching to DOR/3TC/TDF Maintains HIV-1 Virologic Suppression Through Week 144 in the DRIVE-SHIFT Trial

Princy Kumar  1 , Margaret Johnson  2 , Jean-Michel Molina  3 , Giuliano Rizzardini  4 , Pedro Cahn  5 , Markus Bickel  6 , Hong Wan  7 , Zhi Jin Xu  7 , Cristiana Morais  7 , Peter Sklar  7 , Wayne Greaves  7 ; DRIVE-SHIFT Study Group
Affiliations
Clinical Trial

Brief Report: Switching to DOR/3TC/TDF Maintains HIV-1 Virologic Suppression Through Week 144 in the DRIVE-SHIFT Trial

Princy Kumar et al. J Acquir Immune Defic Syndr. .

Abstract

Background: In the primary analysis of the DRIVE-SHIFT trial, switching to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) maintained suppression of HIV-1 through week 48. Here, we present long-term efficacy and safety outcomes through week 144 of the DRIVE-SHIFT trial.

Methods: This phase 3, randomized, open-label trial evaluated switching from a stable antiretroviral regimen to once-daily DOR/3TC/TDF in adults with HIV-1 suppressed for ≥6 months and no previous virologic failure. Participants switched at day 1 [immediate switch group (ISG); n = 447] or week 24 [delayed switch group (DSG); n = 209]. Nine ISG participants who completed week 48 but did not enter extension-1 were excluded from week 144 efficacy analyses.

Results: At week 144, HIV-1 RNA <50 copies/mL was maintained in 80.1% of the ISG (351/438) and 83.7% of the DSG (175/209), while 2.7% (12/438) and 4.8% (10/209), respectively, had HIV-1 RNA ≥50 copies/mL (Food and Drug Administration Snapshot approach). Protocol-defined virologic failure after switch occurred in 2.1% of ISG (9/438) and 3.3% of DSG (7/209); no viral resistance to doravirine was detected in 4 participants with samples available. Reductions in fasting lipids were observed at 24 weeks after switch and maintained through week 144. The mean weight change from switch to week 144 was +1.4 kg for ISG and +1.2 kg for DSG. The most common adverse events were nasopharyngitis (16.2%), headache (12.3%), and diarrhea (9.1%). Overall, 4.1% discontinued because of adverse events, and no deaths occurred.

Conclusions: These results confirm that switching to once-daily DOR/3TC/TDF is a generally well-tolerated option for maintaining viral suppression in adults considering a change in therapy.

Registration: ClinicalTrials.gov NCT02397096.

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Conflict of interest statement

P.K. is on advisory boards for ViiV, Janssen, Merck, and Theratechnologies; has received grants from Merck, ViiV, Gilead, and Theratechnologies; and owns stock in Johnson & Johnson, Gilead, Merck, Pfizer, and GSK. J.-M.M. has participated in advisory boards for Gilead, MSD, ViiV, and Sanofi. G.R. has received consulting/advisor fees from AbbVie, Gilead, MSD, and ViiV, and has board membership with AbbVie, Gilead, MSD, and ViiV. P.C. is an advisory board member for MSD and ViiV and has received research grants from AbbVie, MSD, and ViiV. H.W., Z.J.X., C.M., P.S., and W.G. are current employees of MSD. The remaining authors have no conflicts of interest to declare.

Figures

FIGURE 1.
FIGURE 1.
Virologic outcomes after switch to DOR/3TC/TDF (FDA Snapshot approach). Nine participants in the ISG who completed the base study (with HIV-1 RNA <40 copies/mL) but did not enter extension-1 were excluded from the week 144 analysis. ISG, immediate switch group. DSG, delayed switch group; FDA, Food and Drug Administration.
FIGURE 2.
FIGURE 2.
Weight change after switch to DOR/3TC/TDF. A, Mean change (95% CI), adjusted for weight at time of switch, race (Black/non-Black), ethnicity (Hispanic/others), sex, age, previous therapy class, baseline CD4+ T-cell count, and baseline HIV-1 RNA. B, Proportion of participants by percent change in weight at week 144. CI, confidence interval.
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Comment in

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