'Chemical condoms' for the prevention of HIV infection: evaluation of novel agents against SHIV(89.6PD) in vitro and in vivo.
BACKGROUND
Vaginal agents which are antiviral and/or inhibit the entry of HIV into the cell could prevent heterosexual transmission of HIV, and protect women who cannot negotiate condom use.


METHODS
Four agents have been investigated for activity in vitro and in vivo against SHIV(89.6PD): two anionic polymers, dextrin-2-sulphate (D2S) and PRO 2000 (P2K), and two virucidal agents; a non-ionic detergent, nonoxynol-9 (N9) and a cyclic peptide ionophore, gramicidin-D (GD). All four agents were investigated in rhesus macaques, using an intra-vaginal challenge of two inoculations of 1 x 104 50% tissue culture infectious doses (TCID)50 of SHIV(89.6PD).


RESULTS
D2S, P2K, GD and N9 all inhibited SHIV(89.6PD) in vitro. In vivo, three out of four control macaques were infected as judged by viral culture, seroconversion, DNA and RNA PCR; infection was confirmed in four out of eight 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 four out of four pre-treated with D2S + GD, a combination additive in vitro.


CONCLUSIONS
D2S and PRO-2000, novel inhibitors of HIV entry, showed evidence 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 healthy women which have shown minimal toxicity, support plans for a phase III efficacy trial of chemically simple inhibitors of HIV entry with low toxicity, for the prevention of HIV infection in women.
Weber
J
J
Division of Medicine, Section of Infectious Diseases, Imperial College School of Medicine, St. Mary's Hospital, London UK. j.weber@ic.ac.uk
Nunn
A
A
O'Connor
T
T
Jeffries
D
D
Kitchen
V
V
McCormack
S
S
Stott
J
J
Almond
N
N
Stone
A
A
Darbyshire
J
J
D000282:Administration, Intravaginal; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D003912:Dextrins / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006096:Gramicidin / Q000008:administration & dosage / Q000494:pharmacology; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D008251:Macaca; D008826:Microbial Sensitivity Tests; D009282:Naphthalenesulfonates / Q000008:administration & dosage / Q000494:pharmacology; D017137:Nonoxynol / Q000008:administration & dosage / Q000494:pharmacology; D011108:Polymers / Q000008:administration & dosage / Q000494:pharmacology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000472:pathogenicity
D019380:Anti-HIV Agents; D003912:Dextrins; D009282:Naphthalenesulfonates; C120231:PRO 2000; D011108:Polymers; D006096:Gramicidin; C091377:dextrin 2-sulfate; D017137:Nonoxynol