In Vitro Inactivation of Hiv-1 by Contraceptive Sponge Containing Nonoxynol-9

mentioning

confidence: 99%

Virucidal Efficacy of Soap and Water against Human Immunodeficiency Virus in Genital Secretions

Mack

Levy

2003

“…Clinical trials evaluating the efficacy of N-9 for use as a microbicide demonstrated that N-9 failed to reduce the incidence of HIV-1 infection (22,24,29), despite its potent anti-HIV-1 activity in vitro (13,21). N-9 use was associated with genital inflammation and lesions (19,23,26) and an increased incidence of HIV-1 infection in frequent users of an N-9-containing vaginal gel (28).…”

mentioning

confidence: 99%

Comparative Safety Evaluation of the Candidate Vaginal Microbicide C31G

Catalone¹,

Kish-Catalone²,

Neely³

et al. 2005

C31G is currently the focus of clinical trials designed to evaluate this agent as a microbicidal and spermicidal agent. In the following studies, the in vivo safety of C31G was assessed with a Swiss Webster mouse model of cervicovaginal toxicity and correlated with results from in vitro cytotoxicity experiments and published clinical observations. A single exposure of unformulated 1% C31G resulted in mild-to-moderate epithelial disruption and inflammation at 2 and 4 h postapplication. The columnar epithelium of the cervix was the primary site of damage, while no perturbation of the vaginal mucosa was observed. In contrast, application of unformulated 1.7% C31G resulted in greater levels of inflammation in the cervical epithelium at 2 h postapplication and severe epithelial disruption that persisted to 8 h postapplication. Application of a nonionic aqueous gel formulation containing 1% C31G resulted in no apparent cervicovaginal toxicity at any time point evaluated. However, formulation of 1.7% C31G did not substantially reduce the toxicity associated with unformulated C31G at that concentration. These observations correlate with findings gathered during a recent clinical trial, in which once-daily applications resulted in no adverse events in women receiving the formulation containing 1% C31G, compared to moderate-to-severe adverse events in 30% of women receiving the 1.7% C31G formulation. The Swiss Webster mouse model was able to effectively discriminate between concentrations and formulations of C31G that produced distinct clinical effects in human trials. The Swiss Webster animal model may be a highly valuable tool for preclinical evaluation of candidate vaginal microbicides.

“…This product has been shown to be effective against numerous sexually transmitted pathogens in vitro, including HIV-1 (1,3,4,12,20,21,27,32). However, the in vivo efficacy of nonoxynol-9 against HIV-1 has never been clearly established, and the results of clinical studies are controversial.…”

mentioning

confidence: 99%

Thermoreversible Gel Formulations Containing Sodium Lauryl Sulfate or n -Lauroylsarcosine as Potential Topical Microbicides against Sexually Transmitted Diseases

Roy

Gourde

Piret

et al. 2001

The microbicidal efficacies of two anionic surfactants, sodium lauryl sulfate (SLS) and n-lauroylsarcosine (LS), were evaluated in cultured cells and in a murine model of herpes simplex type 2 (HSV-2) intravaginal infection. In vitro studies showed that SLS and LS were potent inhibitors of the infectivity of HSV-2 strain 333. The concentrations of SLS which inhibit viral infectivity by 50% (50% inhibitory dose) and 90% (90% inhibitory dose) were 32.67 and 46.53 M, respectively, whereas the corresponding values for LS were 141.76 and 225.30 M. In addition, intravaginal pretreatment of mice with thermoreversible gel formulations containing 2.5% SLS or 2.5% LS prior to the inoculation of HSV-2 strain 333 completely prevented the development of genital herpetic lesions and the lethality associated with infection. Of prime interest, no infectious virus could be detected in mouse vaginal mucosa. Both formulations still provided significant protection when viral challenge was delayed until 1 h after pretreatment. Finally, intravaginal application of gel formulations containing 2.5% SLS or 2.5% LS once daily for 14 days to rabbits did not induce significant irritations to the genital mucosa, as demonstrated from macroscopic and histopathologic examinations. These results suggest that thermoreversible gel formulations containing SLS or LS could represent potent and safe topical microbicides for the prevention of HSV-2 and possibly other sexually transmitted pathogens, including human immunodeficiency virus.