A Controlled Trial of Nonoxynol 9 Film to Reduce Male-to-Female Transmission of Sexually Transmitted Diseases

Roddy, Ronald E.; Zekeng, Léopold; Ryan, Kelley A.; Tamoufé, Ubald; Weir, Sharon S.; Wong, Emelita L.

doi:10.1056/nejm199808203390803

Cited by 349 publications

(120 citation statements)

References 26 publications

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“…They are used to orally deliver pain medications, vitamins, and supplements (65)(66)(67). Microbicide drugs, such as dapivirine, retrocyclin-101, cellulose acetate phthalate, and dapivirine in combination with TFV, have been formulated into films for vaginal use, and VCF containing nonoxynol-9, a VCF lubricating film, and a vaginal cleansing film (Apothecus Pharmaceuticals) are all available commercially (25,(28)(29)(30)(31)(32). It is important to evaluate the safety of topical PrEP products, as any breach to the integral mucosal barrier and the associated inflammation promote the recruitment of local CD4 T cells and facilitate HIV infection (68).…”

Section: Discussionmentioning

confidence: 99%

“…Other promising attributes, such as no leakage, lack of feeling the product inside, likelihood to use the product in the future, and acceptability among their male partners were also described for the films (15). A vaginal contraceptive film (VCF) containing the spermicide nonoxynol-9 was the first commercially available film (25). Other feminine hygiene products, including a VCF lubricating film and a vaginal cleansing film, are also marketed.…”

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confidence: 99%

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Safety and Pharmacokinetics of Quick-Dissolving Polymeric Vaginal Films Delivering the Antiretroviral IQP-0528 for Preexposure Prophylaxis

Srinivasan

Zhang

Martin

et al. 2016

Antimicrob Agents Chemother

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dFor human immunodeficiency virus (HIV) prevention, microbicides or drugs delivered as quick-dissolving films may be more acceptable to women than gels because of their compact size, minimal waste, lack of an applicator, and easier storage and transport. This has the potential to improve adherence to promising products for preexposure prophylaxis. Vaginal films containing IQP-0528, a nonnucleoside reverse transcriptase inhibitor, were evaluated for their pharmacokinetics in pigtailed macaques. Polymeric films (22 by 44 by 0.1 mm; providing 75% of a human dose) containing IQP-0528 (1.5%, wt/wt) with and without poly(lactic-co-glycolic acid) (PLGA) nanoparticle encapsulation were inserted vaginally into pigtailed macaques in a crossover study design (n ‫؍‬ 6). With unencapsulated drug, the median ( In the absence of an effective vaccine, preexposure prophylaxis (PrEP) with antiretroviral (ARV) drugs is currently a very promising biomedical intervention to control the human immunodeficiency virus (HIV) epidemic (1, 2). PrEP involves the use of ARV by high-risk HIV-negative individuals to prevent HIV acquisition. Many ARVs that have traditionally been used for HIV treatment have advanced as PrEP agents due to their safety and potency profiles (1,(3)(4)(5). Of the available ARVs, tenofovir disoproxil fumarate (TDF), a nucleoside reverse transcriptase inhibitor (NRTI) used widely in HIV treatment, has been studied extensively in animals and humans as a PrEP agent (3, 5). The success with oral TDF and Truvada, TDF in combination with emtricitabine (FTC), in inhibiting HIV infection in nonhuman primates led to the clinical trials in humans with TDF and Truvada (1, 6-11). In stark contrast to the success of TDF and Truvada in clinical trials in men who have sex with men and heterosexual HIV-discordant couples, two large clinical trials in women with oral Truvada, VOICE and FEM-PrEP, have demonstrated no protection due to a lack of adherence (12, 13).Providing optimal dosage forms of potent HIV PrEP agents for women has the potential to improve product adherence (14,15). Topical dosage forms can be effective in reducing HIV infection, as demonstrated by the CAPRISA 004 vaginal 1% tenofovir (TFV) gel trial, where per-protocol use of the gel before and after sex with no more than 2 doses in 24 h (BAT-24) reduced HIV acquisition by 39% (2). As observed in the oral PrEP trials, greater efficacy was reported among the high adherers in CAPRISA 004 (54% versus 28% in the low adherers) (2). Subsequent trials with 1% TFV gel, such as FACTS 001, employing the BAT-24 regimen used in CAPRISA-004, and the VOICE trial, with a daily application of 1% TFV gel, were not effective in protecting women against HIV acquisition (12, 16). It was estimated based on the returned used applicators that only 13% of the FACTS 001 trial participants were able to use the gel in Ն80% of sex acts per month (16). Neither the noncoital daily application of the TFV gel with VOICE nor the pericoital vaginal dosing regimen with FACTS 001 demonstrated effecti...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Safety and Pharmacokinetics of Quick-Dissolving Polymeric Vaginal Films Delivering the Antiretroviral IQP-0528 for Preexposure Prophylaxis

Srinivasan

Zhang

Martin

et al. 2016

Antimicrob Agents Chemother

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“…The results of these studies justified proceeding to efficacy trials, and two such trials were reported by the end of 1999. 7 8 Their results, and preliminary results from a study in commercial sex workers, suggest that nonoxinol 9 actually increases HIV transmission, probably because of local genital toxicity. The toxicity in these studies may have been associated with frequency of use, and analyses to address this are under way.…”

Section: Status Of Microbicides Tested In Human Trialsmentioning

confidence: 94%

“…Although lack of benefit may seem implausible on the basis of preclinical and early clinical studies, the experience with nonoxinol 9 shows that promising products may prove ineffective or even harmful in efficacy trials. 7 8…”

Section: Challenges For Evaluationmentioning

confidence: 99%

Science, medicine, and the future: Microbicides in HIV prevention

McCormack

Hayes²,

Lacey³

et al. 2001

BMJ

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“…However, around the time these data were published in the 1990s, doubts emerged about the protective effect [12][13][14][15] ; then, studies showed that detergents might actually increase the risk of transmission [16][17][18][19] . It appeared that N-9 can break up the cell lining or irritate the epithelium of the vagina (and the rectum) and that it kills the normal vaginal flora, thus making it easier for a virus or other infective organism(s) to invade.…”

Section: S P E R M I C I D E S a N D S E X U A L L Y T R A N S M I T mentioning

confidence: 99%

State-of-the-art of non-hormonal methods of contraception: II. Chemical barrier contraceptives

Batar

2010

The European Journal of Contraception & Reproductive Health

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Chemical contraceptives mainly known as spermicides are one of the oldest types of contraceptives. The industrial revolution facilitated new developments, and they became a leading and widespread method. However, their use declined in the second half of the 20th century, and came under focus again only with the upsurge of sexually transmitted infections (STIs). The effectiveness of spermicides depends on the users' compliance and pregnancy rates vary widely: from 6/100 woman-year (with perfect use) to 26/100 woman-year (with typical use). Preparations consist of two components: an excipient (foam, cream, jelly, soluble film, suppository or tablet); and a chemical agent with spermicidal properties (acidic compound, microbicidal agent, detergent). The most widely used active agent has been the surface active (detergent) nonoxynol-9 (N-9). Based on their mode of action (surfactant effect of detergents, enzymatic action of microbicides on cell metabolism) spermicides were thought to provide protection against STIs including HIV. Recent studies have, however, shown that detergents may actually increase the risk. Because of this, there is an urgent need for a suitable non-detergent spermicide, and research should focus on developing new compounds to replace N-9 and other agents having similar undesired effects. This paper reviews the latest studies reporting results on these recent developments.

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A Controlled Trial of Nonoxynol 9 Film to Reduce Male-to-Female Transmission of Sexually Transmitted Diseases

Abstract: The use of a nonoxynol 9 vaginal film did not reduce the rate of new HIV, gonorrhea, or chlamydia infection in this group of sex workers who used condoms and received treatment for sexually transmitted diseases.

Cited by 349 publications

References 26 publications

Safety and Pharmacokinetics of Quick-Dissolving Polymeric Vaginal Films Delivering the Antiretroviral IQP-0528 for Preexposure Prophylaxis

Safety and Pharmacokinetics of Quick-Dissolving Polymeric Vaginal Films Delivering the Antiretroviral IQP-0528 for Preexposure Prophylaxis

Science, medicine, and the future: Microbicides in HIV prevention

State-of-the-art of non-hormonal methods of contraception: II. Chemical barrier contraceptives

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