Carraguard<sup>®</sup> Acceptability Among Men and Women in a Couples Study in Thailand

Martin, Sarah; Blanchard, Kelly; Manopaiboon, Chomnad; Chaikummao, Supaporn; Schaffer, Kate; Friedland, Barbara; Kilmarx, Peter H.

doi:10.1089/jwh.2009.1362

Cited by 18 publications

(22 citation statements)

References 45 publications

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“…Additionally, analysis of data from highly adherent participants in the Carraguard (PC-515, 3% CG) Phase 3 trial suggested that CG decreases HPV acquisition (Marais et al, 2011). These data, combined with the excellent safety profile of CG (Crostarosa et al, 2009; Kilmarx et al, 2008; Kilmarx et al, 2006; Martin et al, 2010; Skoler-Karpoff et al, 2008; Turville et al, 2008; Whitehead et al, 2006), have supported clinical testing of PC-515 and Divine 9 gel to prevent HPV. Here we compare the physicochemical properties of both gels, examining their in vitro and in vivo efficacy against different HPV types.…”

Section: Introductionmentioning

confidence: 81%

In vitro and in vivo evaluation of two carrageenan-based formulations to prevent HPV acquisition

et al. 2014

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Commercial vaccines against human papillomavirus (HPV) have low uptake due to parental autonomy, dosing regimen, cost, and cold chain storage requirements. Carrageenan (CG)-based formulations prevent HPV infection in vitro and in vivo but data are needed on the durability of anti-HPV activity and the effect of seminal plasma (SP). The Population Council's PC-515 gel and the lubricant Divine 9 were tested for their physicochemical properties and anti-HPV activity against HPV16, 18, and 45 pseudoviruses (PsVs). Anti-PsV activity was estimated using the luciferase assay in HeLa cells and the HPV PsV luciferase mouse model. Formulations were applied intravaginally either 2 h pre/2 h post (-2 h/+2 h) or 24 h pre (-24 h) relative to challenge with HPV16 or 45 PsV in PBS or SP/PBS. Both formulations showed broad-spectrum anti-HPV activity in vitro (IC50: 1-20ng/ml), significantly decreasing HPV PsV infection in the mouse model (-2h/+2h, p<0.0001). PC-515 protected better than Divine 9 in the -24 h dosing regimen (p<0.0001) and comparable to Divine 9 in the -2 h/+2 h regimen (p=0.9841). PC-515 retained full activity in the murine model when PsV solutions contained human SP. The durable, potential broad-spectrum anti-HPV activity of CG formulations in the presence of SP supports their further development to prevent HPV acquisition.

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Section: Introductionmentioning

confidence: 81%

In vitro and in vivo evaluation of two carrageenan-based formulations to prevent HPV acquisition

et al. 2014

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“…CG represents an excellent delivery vehicle for ZA. It has been shown to be safe and acceptable in numerous preclinical and clinical studies (7,19,22,(25)(26)(27)(28)(29)(30)(31)(32) despite contradictory observations using in vitro systems that CG can enhance HIV infection (22,33). Additionally, CG may have activity against HPV (34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo

Kenney

Rodríguez

Kizima

et al. 2013

Antimicrob Agents Chemother

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We previously showed that a prototype gel comprising zinc acetate (ZA) in carrageenan (CG) protected mice against vaginal and rectal herpes simplex virus 2 (HSV-2) challenge as well as macaques against vaginal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) challenge. In this work, we modified buffers and cosolvents to obtain a stable, nearly iso-osmolal formulation and evaluated its safety and efficacy against SHIV-RT and HSV-2. In vitro toxicity to lactobacilli and Candida albicans was determined. Macaques were given daily doses of ZA and CG (ZA/CG) or CG alone vaginally for 14 days and challenged with SHIV-RT 24 h later. Mice were challenged vaginally or rectally with HSV-2 immediately after a single gel treatment to measure efficacy or vaginally 12 h after daily gel treatment for 7 days to evaluate the gel's impact on susceptibility to HSV-2 infection. The modified ZA/CG neither affected the viability of lactobacilli or C. albicans nor enhanced vaginal HSV-2 infection after daily ZA/CG treatment. Vaginal SHIV-RT infection of macaques was reduced by 66% (P ‫؍‬ 0.006) when macaques were challenged 24 h after the last dose of gel. We observed 60% to 80% uninfected mice after vaginal (P < 0.0001) and rectal (P ‫؍‬ 0.008) high-dose HSV-2 challenge. The modified ZA/CG gel is safe and effective in animal models and represents a potential candidate to limit the transmission of HIV and HSV-2. S everal recent clinical trials have shown that microbicides containing antiretroviral drugs (ARVs) reduce the sexual transmission of HIV and other sexually transmitted diseases (STIs) (1). The Centre for the AIDS Program of Research in South Africa (CAPRISA) 004 trial (CAPRISA-004) showed that pericoital use (before and after sex) of vaginally applied 1% tenofovir (TFV) gel reduced human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus 2 (HSV-2) acquisition by 39% and 51%, respectively (2). Similarly, three oral pre-exposure trials (iPrex, Partners PrEP, and TDF2) targeting men who have sex with men (MSM) and transgender women, HIV-serodiscordant couples, or heterosexual men and women demonstrated between 44% and 73% efficacy (1). Conversely, a lack of efficacy was seen in two trials (FEM-PrEP and VOICE) in which women received daily oral emtricitabine-TFV and TFV (1, 3). A recent analysis of these two studies suggested that the lack of efficacy could have been due to poor regimen adherence (1, 3, 4).Although ARV-containing topical microbicides will likely be available soon, there are important questions regarding their use. (i) Does topical administration of an ARV in people with an undiagnosed HIV infection lead to resistance development and affect their treatment outcomes? (ii) How accessible will these products be (i.e., will they be available over the counter or by prescription only)? (iii) Can the introduction of an HIV-specific microbicide increase the transmission of other STIs?Given these unanswered questions and the potential limitations of ARV-containing topical microbicides, we are ...

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“…Carrageenan gel is an appealing delivery vehicle for rectal microbicides because it has been shown to be safe and acceptable for vaginal use in humans (10,27,28,33,35,45,54), safe when applied to the rectal epithelia of mice (49), and both safe and acceptable rectally in a small human trial (41). Carrageenan also has favorable rheological properties for delivering antiretroviral drugs (12,50).…”

Section: Discussionmentioning

confidence: 99%

“…While Carraguard, a 3% carrageenan gel, was found not to be effective in significantly reducing the number of HIV infections in the treatment arm compared to placebo in a phase 3 clinical trial (45), it was shown to be safe and acceptable by the women who used it in the trial (45) as well as by participants in other studies (27,28,33,35,41,54). Carrageenan-based gels also have favorable rheological properties (12,50), rendering them promising candidates for delivering potent antiviral agents.…”

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confidence: 99%

The Nonnucleoside Reverse Transcriptase Inhibitor MIV-150 in Carrageenan Gel Prevents Rectal Transmission of Simian/Human Immunodeficiency Virus Infection in Macaques

Singer

Derby

Rodríguez

et al. 2011

J Virol

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Carraguard^® Acceptability Among Men and Women in a Couples Study in Thailand

Cited by 18 publications

References 45 publications

In vitro and in vivo evaluation of two carrageenan-based formulations to prevent HPV acquisition

In vitro and in vivo evaluation of two carrageenan-based formulations to prevent HPV acquisition

A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo

The Nonnucleoside Reverse Transcriptase Inhibitor MIV-150 in Carrageenan Gel Prevents Rectal Transmission of Simian/Human Immunodeficiency Virus Infection in Macaques

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Carraguard® Acceptability Among Men and Women in a Couples Study in Thailand

Cited by 18 publications

References 45 publications

In vitro and in vivo evaluation of two carrageenan-based formulations to prevent HPV acquisition

In vitro and in vivo evaluation of two carrageenan-based formulations to prevent HPV acquisition

A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo

The Nonnucleoside Reverse Transcriptase Inhibitor MIV-150 in Carrageenan Gel Prevents Rectal Transmission of Simian/Human Immunodeficiency Virus Infection in Macaques

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Carraguard^® Acceptability Among Men and Women in a Couples Study in Thailand