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Background:  Cytolin® is an anti-LFA-1, mouse, anti-human, monoclonal antibody that binds 4 epitopes of the alpha sub-unit of LFA-1, which is believed to be over-expressed in HIV-infected patients. Cytolin may reversibly inhibit CD8⁺ CTL killing of CD4⁺ T cells; thus, reducing HIV viral load. A phase I study of Cytolin in individuals with HIV showed the drug to be well tolerated. A single 0.1-mg/kg dose was shown to reduce HIV RNA viral load and increase CD4⁺ and CD8⁺ T-cell counts at 56 days. This phase Ia/II study was designed to evaluate multiple doses of Cytolin.

Methods:  A total of 11 subjects received 4 weekly infusions of 1 of 4 doses of Cytolin (0.3 [n = 4], 1.0 [n = 4], and 2.0 [n = 3] mg/kg); 2 additional subjects also received a single infusion (2.0 mg/kg). Eligible patients had viral loads ≥ 10,000 copies/mL, CD4⁺ T-cell counts of 200 to 500 cells/mm³, and a Karnofsky rating of at least 70. Subjects were either treatment naïve or were clinically stable on a fixed antiviral regiment for at least 8 weeks and agreed to remain on the fixed regimen during the study period. Safety (incidence and severity of adverse events, HAMA), efficacy (decrease from baseline in viral load, increase from baseline in T-cell enumeration, and effect on triglycerides and cholesterol), and pharmacokinetics (percentage binding, percentage saturation) were assessed at each visit.

Results:  All adverse effects were mild or moderate. A dose-response effect was observed for HIV-1 viral load; larger decreases from baseline in HIV-1 viral load were observed with increasing doses of Cytolin. After 4 infusions, CD4⁺ T-cell count increased approximately 23% from baseline at day 29 in the multiple-infusion 2.0-mg/kg dose group and correlated with an ~1.0 log decrease from baseline in HIV-1 viral load, which was maintained for at least 50 days from the first infusion, or 28 days from the fourth infusion. Approximately 100% of Cytolin was bound following a single infusion in all dose groups. HAMA reached a maximum accumulation in all dose groups by day 29.

Conclusions:  In this study, 2.0 mg/kg Cytolin had the most pronounced effect on increasing T-cell enumeration and decreasing HIV-1 viral load; the effect of multiple infusions lasted at least 50 days and the effect of a single infusion lasted at least 29 days. Additional studies with 2.0 mg/kg Cytolin are underway to determine the most effective dosing regimen.

Keywords: monoclonal antibody; viral load; HIV