Two-drug HIV regimen as good as B/F/TAF

Among treatment-naïve patients with HIV-1* infection, initial treatment combination with doravirine and islatravir (DOR/ISL) was noninferior in achieving virologic suppression (HIV-1 RNA <50 copies/mL) at week 48 compared with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), according to a trial presented at IAS 2023.

“ISL, an investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI), in combination with DOR, an approved NRTTI, is a potential two-drug regimen with complementary mechanisms of action and resistance profiles,” said Professor Jürgen Rockstroh from the Department of Medicine at the University of Bonn, Germany.

This phase III, double-blind, placebo-controlled trial analysed 597 antiretroviral treatment-naïve patients with HIV-1 (mean age 35.2 years, 25 percent female) who were randomized to receive either DOR 100 mg plus ISL 0.75 mg (n=298) or B/F/TAF (n=299) once daily. Of these, 18.1 percent (DOR/ISL arm) and 20.1 percent (B/F/TAF arm) had high viral load (HIV-1 RNA >100,000 copies/mL) at baseline.

At week 48, DOR/ISL was noninferior to B/F/TAF at achieving HIV-1 RNA <50 copies/mL (88.9 percent vs 88.3 percent; difference, 0.6 percent), with a mean increase in CD4+ T-cell count of 182 and 234 cells/mm³, respectively. [IAS 2023, abstract 5442]

Only one patient in the DOR/ISL arm experienced a confirmed virological failure (defined as two consecutive HIV-1 RNA ≥200 copies/mL) as compared to four patients in the B/F/TAF arm.

Of note, these individuals “started off with a very high viral load of over a million at baseline, and clearly these are more challenging patients to treat … but they still showed a rapid response to treatment with a decrease in viral load of 1,200 copies/mL at week 4,” Rockstroh said.

In terms of safety, the overall rates of treatment-related adverse events (AEs) were similar between the DOR/ISL and B/F/TAF arms (26 percent vs 25 percent).

Serious drug-related AEs occurred in two patients in the B/F/TAF arm, whereas none was reported in the DOR/ISL arm.

COVID-19 (13.8 percent and 16.4 percent), decreased lymphocyte count (11.7 percent and 6.4 percent), and headache (10.7 percent for both arms) were the most frequent AEs reported between the DOR/ISL and B/F/TAF arms, respectively.

In spite that more DOR/ISL recipients had reduced CD4+ T-cell or total lymphocyte counts than the B/F/TAF recipients (5.4 percent vs 2.0 percent), “these changes in lymphocyte count did not lead to any difference in the incidence of infectious-related AEs,” noted Rockstroh.

Similarly, both DOR/ISL and B/F/TAF arms showed no statistical difference in weight gain from baseline to week 48 (3.45 vs 3.32 kg; difference, 0.15 kg).

“Overall, the new investigational combination of DOR/ISL … was noninferior to B/F/TAF for initial treatment of HIV-1 … and was generally well tolerated,” said Rockstroh.

“As you may have followed, the phase III clinical development of DOR/ISL has been resumed with a different dose for ILS, 0.25 mg once daily, in patients with HIV-1 who were naïve to treatment and virologically suppressed,” he added.