ABX464 nudges viral reservoir but not time to viral rebound
28 November 2017. Related: Conference reports, Antiretrovirals, Cure-related research, EACS 16 Milan 2017.
Simon Collins, HIV i-Base
New data presented at EACS 2017 suggested that the investigational REV inhibitor ABX464 might reduce the viral reservoir in a study that included a treatment interruption. [1]
The ABX464-004 study randomised (3:1) 30 participants on stable ART (CD4 nadir >350) who had been taking boosted darunavir monotherapy for at least 8 weeks to either add ABX464 (mainly 150 mg) or matched placebo for 28 days, after which all treatment was stopped. Full ART was restarted if viral load rebounded to >1000 copies/mL.
The impact on viral reservoir was measured by total HIV DNA in PBMCs with response defined as minimum reduction of 50 copies/million PBMCs and >25% decrease in HIV DNA copies.
Baseline characteristics included median duration of HIV infection of 10.2 years with median 5.6 years on ART.
In the 15 subjects with validated viral DNA results, 8/15 (53%) of the active group reported significant reductions (mean change of – 38% (95%CI: -27% to -67%], with a mean decrease of 185 copies/million PBMCs (95%CI: -434 to -82) compared to no responders in the placebo group (0/4).
However, there were no differences between groups in time to viral rebound after stopping ART: mean 13 vs 14 days for ABX464 vs placebo groups respectively.
Tolerability was good with no serious side effects reported in the treatment group.
ABX464 blocks the end stages of viral assembly. Results on antiviral efficacy from an earlier phase 2a dose-ranging study in 80 treatment-naive participants in Thailand reported modest antiviral activity (~0.5 log copies/mL) but only in 4/6 people using the highest 150 mg dose (with no responses in 2/6). [2]
Future studies are planned to use ABX464 with triple therapy ART using longer treatment with ABX464 (64 days) (study 005), in people suppressed in chonic infection (study 006) ad those treated in acute infection (study 007).
References:
- Vandekerckhove L et al. ABX464 decreases total HIV DNA in PBMC´s when administered during 28 days to HIV-infected patients who are virologically suppressed. 16th European AIDS Conference, 25–27 October 2017, Milan. Oral abstract PS1/7.
- Scherrer D et al. Early evidence of antiviral activity & safety of ABX464 in HIV treatment-naïve patients. CROI 2016, February 22–25, Boston, Late breaker poster abstract 461LB.
http://www.croiconference.org/sessions/early-evidence-antiviral-activitysafety-abx464-hiv-treatment-naïve-patients (abstract and poster)