Background
For some individuals with HIV-1 infection who have failed multiple antiretroviral regimens and have limited treatment options, there is an urgent need for new antiretroviral drugs with novel mechanisms of action. Albuvirtide (ABT) is an HIV-1 fusion inhibitor and 3BNC117 is an HIV-specific, broadly neutralizing monoclonal antibody. We aimed to assess the efficacy and safety of ABT+3BNC117 combined with an optimized background regimen (OBR) in adults with multidrug-resistant (MDR) HIV-1.
Methods
In this ongoing phase 2 trial in two countries, we enrolled patients with MDR HIV-1 infection who had failed multiple antiretroviral therapies. All participants had a viral load over 1000 copies of HIV-1 RNA per mL. After a control period (day 0 to day 6) during which participants continued their current therapy, ABT+3BNC117 was infused on days 7, 8, and 9, and the viral load was then measured at week 2 (treatment period). On day 14, all eligible participants were randomly assigned in a 1:1 ratio to Group A (receiving ABT weekly and 3BNC117 biweekly) or Group B (receiving both ABT and 3BNC117 biweekly), combined with an OBR that included at least one fully active agent for the same 24-week maintenance period. The primary endpoint was the proportion of participants who experienced a reduction in viral load of at least 0.5 log10 RNA copies/mL between day 7 and day 14.
Results
A total of 16 participants completed the study. The mean baseline viral load was 4.45 log10 RNA copies/mL. Of the 16 participants in the intention-to-treat population, 10 (62.5%) had a decrease in viral load of at least 0.5 log10 RNA copies/mL from baseline (p<0.001 for the comparison with the control period). At the end of treatment (EOT), participants who had received ABT+3BNC117 plus OBR had a mean decrease in viral load of 2.52 log10 RNA copies/mL from baseline, with 87.5% achieving levels below 50 RNA copies/mL. At week 26, 75% of Group A and 100% of Group B had a viral load below 50 RNA copies/mL. 2 participants had virologic failure. No participants died from causes related to underlying illnesses and no serious adverse events related to ABT+3BNC117 were identified. In the eight-week analysis after ABT+3BNC117 cessation in 14 participants, 92.8% had a viral load below 50 RNA copies/mL.
Conclusions
In patients with MDR HIV-1 infection who have advanced disease and limited treatment therapeutic options, the combination of ABT+3BNC117 had significant antiviral activity during a 34-week study period.