Antiretroviral Activity of AMD11070 (An Orally Administered CXCR4 Entry Inhibitor): Results of NIH/NIAID AIDS Clinical Trials Group Protocol A5210

AMD11070 binds to the chemokine receptor CXCR4, with anti-HIV-1 activity and . We conducted a phase IB/IIA proof-of-concept dose-escalating, open-label study to determine safety and antiviral activity of AMD11070 administered over 10 days to HIV-1-infected participants who harbored CXCR4-tropic virus. Primary endpoints were ≥1 log rlu (relative luminescence units) reduction in CXCR4-tropic virus during 10 days of AMD11070 treatment or in the 7 days following treatment discontinuation, rlu changes over 10 days of treatment, and safety. Plasma pharmacokinetic parameters, HIV-1 RNA, and safety labs were obtained over 90 days of study. The study was stopped early due to emerging AMD11070 animal toxicity data. Six HIV-infected participants with plasma HIV-1 RNA ≥5,000 copies/mL on no antiretroviral therapy for 14 days before entry were treated. AMD11070 was well-tolerated when administered at 200 mg orally every 12 h for 10 days. All enrolled participants had dual/mixed (D/M) viruses. Reductions of almost 1 log rlu or more in CXCR4 virus were seen in three of six participants after 10 days of treatment. No participants had ≥1 log decline in plasma HIV-1 RNA from baseline at day 10. No clear relationship between pharmacokinetic parameters and response to therapy (X4 log rlu reduction) was observed. AMD11070 demonstrated activity as measured by reductions in CXCR4 rlu signal. Despite the finding of discordant rlu and plasma HIV RNA responses in these participants with D/M viruses, exploration of other HIV-1 CXCR4 antagonist therapies is possible.