A potential approach to preventing HIV infection in women is reported in an online publication from Nature. John Moore and his colleagues tested a vaginal microbicide containing up to three small-molecules or peptides that inhibit HIV-1 entry into cells, to see if they protected macaque monkeys from vaginal infection. They found that combinations of inhibitors delivered in a topical microbicide gel provided substantial protection against infection.
The HIV virus enters human T cells via surface molecules, or receptors. The protein CCR5 is important for the initial infection. One of the small molecules binds directly to the CCR5 receptor, the other binds to the virus gp120 envelope protein to prevent receptor binding. The third inhibitor, a peptide, blocks entry after the receptors have been engaged, allowing the team could inhibit several different stages of virus attachment and entry.
The team tested different combinations and concentrations of the inhibitors, alone and together, which were administered in a vaginal gel. The monkeys were then exposed to simian HIV (SHIV) and their infection rates monitored. The extent of protection was striking, using both single inhibitors and combinations of them. In a small-scale, exploratory experiment, several macaques were protected even when the microbicide was delivered up to 6 hours before exposure to simian HIV.
One advantage of using small molecules as a microbicide is that production costs may not be prohibitive. Clinical trials are needed to assess safety and efficacy in HIV infection in women.
John Moore (Weill Medical College, Cornell University, New York, NY, USA)
Tel: +1 212 746 4462; E-mail: firstname.lastname@example.org
Abstract available online.
(C) Nature press release.
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