| Summary: | Topical microbicides are being developed as a female-controlled method for preventing HIV-1 infection. Non-antiretroviral (ARV)-based candidates may be advantageous given increasing levels of ARV resistance in low and middle- income countries. MABGEL 1 was a phase 1 trial designed to evaluate the pharmacokinetics and safety of a vaginal microbicide containing the broadly HIV-1 neutralizing monoclonal antibodies (mAbs) C2F5, C4E10 and C2G12 in a hydroxyethylcellulose-based gel vehicle. It was the first study of topical mAb application to the human female genital tract. Twenty-eight healthy women were randomised to apply either high dose Mabgel (containing 20mg/g of each mAb) (n= 10), low dose Mabgel (containing 10mg/g of each mAb) (n=9) or placebo gel (n=9). Doses (2.5ml) were applied over 12 consecutive days. Genital tract sampling was performed at baseline, 1 hour, 8 hours and 24 hours post 1st dose and 12 and 36 hours post 12th dose with serum samples collected at baseline, 8 hours post 1st dose and 12 hours post 12th dose. Safety was assessed through participant report and clinical examination, including colposcopy. Residence half-lives (t ½) in vaginal secretions (Weck-Cel samples) were estimated to be between 4 and 5.5 hours for C4E10 and C2F5. In contrast, vaginal levels of C2G12 did not conform to a single overall exponential decay, displaying a more rapid initial rate of decline, which then slowed at lower concentrations. The estimated early t ½ of C2G12 was 1.4 hours (95% CI 1.2 to 1.8). There was no evidence of systemic absorption. Daily vaginal application of up to 50g of each mAb over 12 days was safe. Although adverse events (AEs) were reported by all but 1 participant, 95 % were mild, none were serious and only 4 were moderate. There was no statistically significant difference in the number of AEs reported per participant between the 3 study arms. Although there are a number of caveats, results demonstrate ‘proof of principle’ of the potential for combinations of HIV-1 neutralizing mAbs to be used as a coitally-dependent microbicide.
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