Glasgow 2022: Impact of islatravir on lymphocyte counts in a dose-ranging study: a post-hoc analysis

HIV Glasgow included a late-breaking post-hoc analysis of islatravir (ISL) dose-ranging studies (0.25 mg, 0.75 mg and 2.25 mg) that led to most clinical studies being stopped last December due to safety concerns over a decline of CD4 counts. [1, 2]

Total lymphocyte, CD4 and B cell counts were reduced by the greatest extent at the highest dose of ISL (2.25 mg). A 3-fold dose reduction from 2.25 to 0.75 mg improved cell counts. Changes in total lymphocyte and CD4 cell counts were comparable for 0.25 mg ISL and standard ART.

Other haematological parameters (haemoglobin, platelets, and neutrophils) were not affected.

Post-hoc analysis was performed for protocol 11, which included participants that received either ISL (0.25, 0.75 or 2.25 mg) plus DOR/3TC or DOR/3TC/TDF. ISL was standardised to 0.75 mg at week 60, and all participants were switched to ISL/DOR (0.75/100 mg) at week 144 and followed for a year.

At week 72, total lymphocytes counts were +20.5%, –0.4% and –15.9% compared to baseline for 0.25, 0.75 and 2.25 mg ISL, respectively. CD4 counts changed by +24.0% (2.25 mg ISL), +47.1% (0.75 mg ISL), +79.8% (0.25 mg ISL) and 60.1% (DOR/3TC/TDF).

A 3-fold reduction of ISL from 2.25 mg to 0.75 mg increased lymphocyte (21.2%) and CD4 (28%) counts. Conversely, a 3-fold increase of ISL (0.25 mg to 0.75 mg) led to reduced lymphocyte (10.8%) and CD4 (1.8%) counts.

Adverse events relating to other infections were common across all arms of the study with prevalence rates of 71% (DOR/3TC/TDF), 58.1% (2.25 mg ISL), 73.3% (0.75 mg ISL) and 65.5% (0.25 mg ISL).

There were two AIDS-defining events that were not linked to ISL.

References

1. Correll T et al. Total lymphocyte and lymphocyte subset changes in participants receiving islatravir (0.25, 0.75 and 2.25mg QD) and doravirine (DOR) +/- lamivudine (3TC): post-hoc analysis from a phase 2b dose-ranging study (P011). Oral 46. HIV Glasgow, 23 to 26 October 2022.
   https://onlinelibrary.wiley.com/doi/10.1002/jia2.26009 (abstract)
   https://virtual.hivglasgow.org/programme/late-breakers-hot-topics (webcast)
2. Collins S. FDA further limit use of islatravir in ongoing studies. HTB (20December 2021).
   https://i-base.info/htb/41866