10th Conference on Retroviruses and Opportunistic Infections Boston, MA USA - February 10 -14, 2003

Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 16
Z. Ambrose¹, C. Miller², L. Compton², J. Hildreth³, J. Lifson¹, V. KewalRamani^1
1Natl. Cancer Inst., Frederick, MD; ²California Regional Primate Res. Ctr., Davis; and ³Johns Hopkins Univ., Baltimore, MD

BACKGROUND: Sexual transmission accounts for greater than 90% of worldwide HIV infection. Moreover, the incidence and prevalence of HIV infection in women has been increasing. Vaginal microbicides provide a female-controlled strategy to prevent HIV transmission. We have chosen to evaluate an HIV inactivating agent, 2-hydroxypropyl-betacyclodextrin (BCD) as a potential microbicide. Significantly, BCD recently has been proven as an effective microbicide in a mouse model for intravaginal HIV-1 transmission and is used extensively for other purposes in individuals.

METHODS: First, we evaluated the efficacy of virus neutralization in vitro, using a single cycle replication assay with HIV or SIV in the presence or absence of BCD. Based on this data, we administered BCD intravaginally in rhesus macaques, followed by inoculation with highly pathogenic SIV. Control animals were treated with gel alone or nothing before inoculation with the same dose of SIV. The animals have been evaluated for infection by RT-PCR of gag sequences in their plasma and nested PCR of gag sequences in their PBMC. These animals continue to be monitored for antiviral humoral and cellular immune responses.

RESULTS: BCD was successful in neutralizing both HIV and SIV in vitro. In fact, we could not see outgrowth of virus after 30 days in culture. Our in vivo preliminary data indicate that intravaginal pretreatment with BCD significantly reduces SIV mucosal transmission relative to untreated control animals. Currently we are performing repeated challenges with BCD and SIV in the uninfected animals to assess whether they continue to be protected from infection. In addition, we are determining whether or not the uninfected BCD-treated animals have antiviral immune responses as compared to the controls.

CONCLUSIONS: Should BCD continue to prevent SIV transmission and not perturb mucosal tissues in this model, its current approved use in humans suggests it would be an important candidate for clinical consideration for use as an anti-HIV microbicide.

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Copyright © 2003 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.