J. Weber et al., 'Chemical condoms' for the prevention of HIV infection: evaluation of novel agents against SHIV89.6PD in vitro and in vivo, AIDS, 15(12), 2001, pp. 1563-1568
Background: Vaginal agents which are antiviral and/or inhibit the entry of
HIV into the cell could prevent heterosexual transmission of HIV, and prote
ct women who cannot negotiate condom use.
Methods: Four agents have been investigated for activity in vitro and in vi
vo against SHIV89.6PD: two anionic polymers, dextrin-2-sulphate (D2S) and P
RO 2000 (P2K), and two virucidal agents; a non-ionic detergent, nonoxynol-9
(N9) and a cyclic peptide ionophore, gramicidin-D (GD). All four agents we
re investigated in rhesus macaques, using an intra-vaginal challenge of two
inoculations of 1 x 10(4) 50% tissue culture infectious doses (TCID)(50) o
f SHIV89.6PD.
Results: D2S, P2K, GD and N9 all inhibited SHIV89.6PD in vitro. In vivo, th
ree out of four control macaques were infected as judged by viral culture,
seroconversion, DNA and RNA PCR; infection was confirmed in four out of eig
ht macaques pre-treated with P2K, two out of four pre-treated with D2S, one
out of four pre-treated with N9, two out of four pre-treated with GD and f
our out of four pre-treated with D2S + GD, a combination additive in vitro.
Interpretation: D2S and PRO-2000, novel inhibitors of HIV entry, showed evi
dence of protection in vivo, comparable to that seen with the virucide, N9.
These data, together with the results of phase I and phase II studies in h
ealthy women which have shown minimal toxicity, support plans for a phase I
II efficacy trial of chemically simple inhibitors of HIV entry with low tox
icity, for the prevention of HIV infection in women. (C) 2001 Lippincott Wi
lliams & Wilkins.