BufferGel: Results of the First Phase I Study of a Novel Vaginal Microbicide

Objective: To evaluate the safety and tolerability of BufferGel (ReProtect LLC: IND #49,744), a negatively charged, non-absorbable high molecular weight polymer gel, designed to maintain vaginal pH below 5 in the presence of semen.

Design: A Phase I study was designed which initially screened 38 low risk abstinent or sexually-active monogamous women in Rhode Island who consented to a pelvic exam. 11 were not enrolled because of baseline infection, mucosal disruption, or lack of willingness to participate once they learned what the protocol entailed.

Methods: Participants underwent baseline colposcopy at baseline, and after 14 days of product use once a day, with a speculum on day 7. Participants with no abnormalities at day 14 then used the product twice a day, with the same clinical evaluation protocol. Primary safety/toxicity endpoints were: systemic toxicities or mucosal ulceration, abrasion, severe erythema and/or edema. They also were interviewed to assess acceptability.

Results: 16 sexually abstinent and 11 monogamous women used the product once or twice a day. Male partners were instructed to always use condoms. No serious adverse events (AE) were seen; 18 participants reported AE's, with all but 4 noting mild symptoms. Only one AE was probably/possibly drug-related. AE's tended to be superficial and self-limited; the most common symptom was vaginal pruritus. There was no evidence to suggest that AE's correlated with dose frequency. After initiation of product use, 3 women were withdrawn; two developed vaginal candidiasis, one developed a hyperkeratotic lesion. Median baseline vaginal pH was 4.6, and on product was 4.5 or less in 93% of 82 determinations; the median pH decrease from baseline levels was 0.55 after 7 days, and 0.30 after 14 days, with once daily product use. Acceptability questionnaires, diaries, and focus groups suggested a high level of willingness to use the product if it were available.

Conclusions: The rationale for the use of BufferGel as a microbicide is its ability to maintain a low pH which inhibits HIV replication. BufferGel appears to be non-toxic and well-tolerated by low risk U.S. women, and capable of maintaining a low vaginal pH, used either once or twice daily. Further studies of BufferGel are currently underway overseas.

Kenneth Mayer
Brown University AIDS Program
Providence, Rhode Island