| |
2 Doravirine+Islatravir Studies Published
|
| |
| |
Download the PDF
Download the PDF
Download the PDF
May 08, 2024
Population pharmacokinetic modelling using data from the islatravir clinical programme predicts that islatravir (0⋅25 mg) will provide robust antiviral activity without a negative effect on lymphocytes.30, 31 Therefore, the development of once-daily doravirine and islatravir has been transitioned from islatravir 0⋅75 mg to 0⋅25 mg, and clinical trials have been initiated to evaluate the fixed combination of doravirine (100 mg) and islatravir (0⋅25 mg) once daily in people with HIV-1 who are virologically suppressed (NCT05631093, NCT05630755) or naive to treatment (NCT05705349).
Switch to DOR/Islatravir Once Daily from Biktarvy
Findings
We screened 726 individuals for eligibility between Feb 18 and Sept 3, 2020, of whom 643 (88⋅6%) participants were randomly assigned to a treatment group (183 [28⋅5%] women and 460 [71⋅5%] men). 322 participants were switched to doravirine (100 mg) and islatravir (0⋅75 mg) and 321 continued bictegravir, emtricitabine, and tenofovir alafenamide (two participants [one with a protocol deviation and one who withdrew] assigned to bictegravir, emtricitabine, and tenofovir alafenamide did not receive treatment). The last follow-up visit for the week 48 analysis occurred on Aug 26, 2021.
At week 48, two (0⋅6%) of 322 participants in the doravirine and islatravir group compared with one (0⋅3%) of 319 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group had greater than or equal to 50 HIV-1 RNA copies per mL (difference 0⋅3%, 95% CI -1⋅2 to 2⋅0).
The per-protocol analysis showed consistent results. 25 (7⋅8%) participants in the doravirine and islatravir group had headache compared with 23 [7⋅2%] participants in the bictegravir, emtricitabine, and tenofovir alafenamide group; 101 (31⋅4%) compared with 98 (30⋅7%) had infections; and eight (2⋅5%) participants in each group discontinued therapy due to adverse events. 32 (9⋅9%) participants had treatment-related adverse events in the islatravir and doravirine group comapred with 38 (11⋅9%) in the bictegravir, emtricitabine, and tenofovir alafenamide group.
In the islatravir and doravirine group, CD4 cell counts (mean change -19⋅7 cells per μL) and total lymphocyte counts (mean change -0⋅20 x 109/L) were decreased at 48 weeks.
Switch to DOR/Islatravir from ART
Findings
Between Feb 18 and Oct 2, 2020, 740 individuals were screened for eligibility, of whom 672 (90⋅8%) participants (249 [37⋅1%] women and 423 [62⋅9%] men; median CD4 count of 678 cells per μL [IQR 496-868]) were randomly assigned to doravirine (100 mg) and islatravir (0⋅75 mg; n=336) or to continue baseline ART (n=336). The last follow-up visit occurred on Sept 8, 2021.
At week 48, zero of 336 participants in the doravirine and islatravir group versus five (1⋅5%) of 336 participants in the baseline ART group had greater than or equal to 50 HIV-1 RNA copies per mL (difference -1⋅5, 95% CI -3⋅4 to -0⋅3).
The per-protocol analysis showed consistent results. Headache was the most common adverse event in both groups (35 [10⋅4%] of 336 participants in the doravirine and islatravir group, 16 [4⋅8%] of 336 in the baseline ART group), infection rates were similar (113 [33⋅6%] in both groups), and discontinuations due to adverse events were low (seven [2⋅1%] vs one [0⋅3%]). 66 (19⋅6%) of 336 participants had treatment-related adverse events in the doravirine and islatravir group compared with 30 (8⋅9%) of 336 in the baseline ART group.
In the islatravir and doravirine group, CD4 cell counts (mean change -30⋅3 cells per μL) and total lymphocyte counts (mean change -0⋅26 x 109/L) were decreased at 48 weeks.
|
|
| |
| |
|
|
|
