Elsevier

The Lancet

Volume 361, Issue 9359, 1 March 2003, Pages 785-786
The Lancet

Correspondence
Need for a true placebo for vaginal microbicide efficacy trials

https://doi.org/10.1016/S0140-6736(03)12645-1Get rights and content

Cited by (9)

  • The rise and fall of polyanionic inhibitors of the human immunodeficiency virus type 1

    2011, Antiviral Research
    Citation Excerpt :

    Therefore, Carraguard was determined to be ineffective with respect to the prevention of vaginal transmission of HIV-1 (Skoler-Karpoff et al., 2008). However, the results of this trial may have been compromised by a number of factors, including infections due to anal intercourse, the use of methylcellulose as a placebo that may provide a barrier to HIV-1 infection, and the incidence of use (Coetzee et al., 2001; Kilmarx and Paxton, 2003). In this trial, the applicators were examined for the presence of vaginal proteins to determine if the applicators were actually inserted into the vagina (Wallace et al., 2004, 2007).

  • Semi-solid gels function as physical barriers to human immunodeficiency virus transport in vitro

    2010, Antiviral Research
    Citation Excerpt :

    This was a gel placebo-controlled trial. The possible prophylactic activity of placebo gels in clinical trials is recognized as a deficiency of blinded, placebo-controlled clinical trial designs for microbicides, since it could reduce the estimated effectiveness of the test gels from its actual value (Kilmarx and Paxton, 2003; Lagakos and Gable, 2008). However this effect, while unknown, is likely low.

  • Dynamics of HIV neutralization by a microbicide formulation layer: Biophysical fundamentals and transport theory

    2006, Biophysical Journal
    Citation Excerpt :

    Achievement of the former may not be trivial. (12,43) Moreover, the transport model here has reinforced this need for valid placebos in clinical trials (44,45), because the results clearly show any diffusive restriction by a placebo coating layer would substantially increase viral residence time within the vagina, thereby exposing it to the body’s natural defenses (low pH, hydrogen peroxide, innate antiviral proteins, etc.) and possibly provide a protective effect. (5,45) Any anti-HIV efficacy by placebo would have serious consequences in a randomized, controlled, clinical trial, because it would reduce the difference between the prophylactic effects of the test product and its control.

  • Erosion of microbicide formulation coating layers: Effects of contact and shearing with vaginal fluid or semen

    2005, Journal of Pharmaceutical Sciences
    Citation Excerpt :

    This distinction could have influenced differential infection rates in the COL-1492 study. Our results present biophysical evidence that reinforces arguments for a biologically and biophysically relevant placebo in future microbicide studies.28,30 The rapid (<30 min) and significant (>50%) decreases in gel viscosity after exposure to ambient vaginal fluids suggest that coating layer erosion is likely to occur in vivo.

  • Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomised, double-blind, placebo-controlled trial

    2008, The Lancet
    Citation Excerpt :

    However, these percentages could be underestimates, since stigma, especially in sub-Saharan Africa, often leads to reduced reports of anal sexual intercourse in women.38–40 Finally, methylcellulose might not be a true placebo.30,41 Despite preclinical data showing that methylcellulose has no anti-HIV effect, its physical properties might reduce HIV transmission when used vaginally, which would make detection of whether or not Carraguard is effective difficult.

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