Second-generation HIV microbicides: Continued development of griffithsin

Abstract

We are now more than 25 years into the AIDS pandemic and our main technological intervention for preventing vaginal and rectal transmission of HIV remains the condom. Although capable of providing significant protection if used regularly, condoms (male and female) are used inconsistently, and there is a clear need for additional prevention technologies. Vaginal microbicides are one such woman-controlled technology that may have higher acceptability, and consequently be used more regularly, than condoms. The report by O'Keefe et al. (1) in this issue of PNAS describes a promising, highly potent microbicide candidate, griffithsin, a red algal lectin that acts as an HIV entry inhibitor. The authors also report successful use of a versatile, rapid, and scaleable Nicotiana benthamiana -based manufacturing system for recombinant proteins, a critical step, because any microbicide would be used by millions of people. Large-scale HIV prevention clinical trial results have been disappointing for the first generation of microbicide candidates (Fig. 1): nonxoynol-9, cellulose sulfate, and Savvy showed a potential increase in HIV transmission (2); Carraguard and BufferGel showed no effect (3, 4). Only PRO 2000 demonstrated a trend toward reduction in HIV transmission (30%; ref. 4). These gels were applied temporally close to intercourse, and … 1To whom correspondence should be addressed. E-mail: larry.zeitlin{at}mappbio.com