CROI 2025: Switching to daily fixed-dose doravirine/islatravir: two randomised phase 3 studies

20 March 2025. Related: Conference reports, Antiretrovirals, .

Simon Collins, HIV i-Base

Two similar studies shared an oral presentation to report 48-week results from two international phase 3 studies switching people undetectable on current ART to a daily oral fixed-dose dual combination (FDC) of doravirine/islatravir (100 mg/0.25 mg).

In the first study, Amy Colson from Community Resource Initiative, Boston, presented results from a randomised (2:1) placebo-controlled study in 513 participants who were currently undetectable on B/F/TAF.

Mean age was 47 (±12), 60% were white, 30% were Black/African American and 22% were Latinx. The study reported 21% were women ‘at birth’ with no detail about current gender or whether any participants were transgender.

Participants had been diagnosed for a median of 11 years (IQR: 4 to 19) and had been on B/F/TAF for 3.4 years (IQR: 2.0 to 5.0). Median CD4 counts were high (691 (IDR: 499 to 882) with 91% >350 cells/mm3. Also, 25% were HBV core antibody positive.

At week 48, viral load was detectable ≥50 copies/mL in 5 (1.5%) vs 1 (0.6%) participants on DOR/ISL vs B/F/TAF respectively; difference 0.9% (95% CI:  –1.9 to +2.9). this showed non-inferiority using upper margin 4%. Viral load was <50 copies/mL in 91% vs 94%, with missing data for 7% vs 5%, respectively.

One participant on DOR/ISL discontinued due to lack of efficacy with no on-treatment resistance detected at the time of viraemia. Adverse events were similar between groups and there were no differences in CD4 T-cell or total lymphocyte count.

However, 2 vs 1 participants in each group discontinued because of significant decreases in CD4 or total lymphocytes. One was still less than 500 copies/mL at week 36 with good drug levels and no resistance. The second had ‘high level’ (but not specified) viraemia at week 48 without detectable drug levels. Both resuppressed on B/F/TAF.

Tolerability and side effects were similar in each arm. Body weight was stable and similar in both arms: mean weight change was –0.03 vs +0.28 in the DOR/ISL vs B/F/TAF groups respectively; difference 0.3, (95%CI: 1.13 to 0.53).

There were no cases of HBV reactivations, but two discontinuations in the DOR/ISL group due to new HBV infections.

In the second study, presented by Chloe Orkin from Queen Mary University of London, 551 participants were randomised (2:1) to either open-label DOR/ISL or to remain on a range of current ART combinations.

Baseline demographics were similar to the previous study. Median age was 51 (IQR: 41 to 59), 39% were white, 45% were Black/African American and 14% were Latinx. The study reported 39% were women, again ‘at birth’ with no detail about current gender or whether any participants were transgender.

Participants had been diagnosed for a median of 13 years (IQR: 7 to 20) and had been on current ART for 3.8 years (IQR: 2.0 to 6.3), with 64% on INSTI-based and 35% on NNRTI-based ART. Median CD4 counts were also high at 706 cells/mm3 (IQR: 545 to 921) with 91% >350 cells/mm3 and 29% were HBV core antibody positive.

At week 48, viral load was ≥50 c/mL in 4 (1.4%) vs 9 (4.9%) participants on DOR/ISL vs B/F/TAF respectively; difference –3.6% (95% CI:  –7.8 to –0.9). This showed non-inferiority using upper margin 4%. Viral load was <50 copies/mL in 95% vs 91%, with missing data for 3.0% vs 3.2%, respectively.

There were five discontinuations on DOR/ISL due to viral failure. Two were at week 4 with baseline drug resistance that should have been exclusion criteria. Three with viral failure at week 48 included one with baseline resistance, one with new T215T and one sample not amplified.

Although more drug-related side effects were reported with DOR/ISL (12% vs 5%), discontinuations were similar (0.3% vs 1.1%). Also, although there was more weight gain with DOR/ISL (+0.9 kg vs –0.1 kg), this was driven by participants switching away from efavirenz or TDF (+2.34 kg vs +0.09 kg).

There were no differences between groups in CD4 or lymphocyte changes.

References

  1. Colson AE et al. Switch to DOR/ISL (100/0.25 mg) QD From BIC/FTC/TAF: A Blinded Phase III Study in Adults With HIV-1. CROI 2025. Oral abstract 204A.
    www.croiconference.org/abstract/3699-2025 (abstract)
    watch.croiwebcasts.org/2025croi/ap/54370 (webcast for delegates)
  1. Orkin C et al. Switch to DOR/ISL (100/0.25 mg) QD From Oral ART: An Open-Label Phase III Study in Adults With HIV-1. CROI 2025. Oral abstract 204B.
    www.croiconference.org/abstract/3707-2025 (abstract)
    watch.croiwebcasts.org/2025croi/ap/54371 (webcast for delegates)

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