Absorption from the Vagina

Benziger, David P.; Edelson, Jerome

doi:10.3109/03602538308991387

Cited by 80 publications

(24 citation statements)

References 98 publications

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“…Assuming that ARV-based microbicides will be low-risk is reasonable because systemic absorption has not been found in phase I trials of intravaginal application of ARV-based microbicides (e.g., tenofovir, UC-781, and TMC-120) (3,11,12). However, assuming that they will be high-risk is also reasonable because the vagina is highly permeable (13)(14)(15)(16) and is often an ideal route for drug administration (17)(18)(19)(20)(21). Hence, in all of our analyses, we investigate the potential impact of both types of microbicides.…”

Section: The Paradoxical Effects Of Using Antiretroviral-based Microbmentioning

confidence: 99%

The paradoxical effects of using antiretroviral-based microbicides to control HIV epidemics

Wilson

Coplan

Wainberg

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Vaginal microbicides, designed to prevent HIV infection in women, are one of the most promising biomedical interventions. Clinical trials of second-generation microbicides have begun; if shown to be effective, they could be licensed within 5–10 years. Because these microbicides contain antiretrovirals (ARVs), they could be highly effective. However, there is concern that, if used by HIV-positive women, ARV resistance may evolve. By analyzing a mathematical model, we find that adherence could have both beneficial and detrimental effects on trial outcomes. Most importantly, we show that planned trial designs could mask resistance risks and therefore enable high-risk microbicides to pass clinical testing. We then parameterize a transmission model using epidemiological, clinical, and behavioral data to predict the consequences of wide-scale usage of high-risk microbicides in a heterosexual population. Surprisingly, we show that reducing a participant's risk of resistance during a trial could lead to unexpectedly high rates of resistance afterward when microbicides are used in public health interventions. We also find that, paradoxically, although microbicides will be used by women to protect themselves against infection, they could provide greater benefit to men. More infections in men than in women will be prevented if there is a high probability that ARVs are systemically absorbed, microbicides are less than ∼50% effective, and/or adherence is less than ∼60%. Men will always benefit more than women in terms of infections prevented per resistant case; but this advantage decreases as the relative fitness of drug-resistant strains increases. Interventions that use ARV-based microbicides could have surprising consequences.

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Section: The Paradoxical Effects Of Using Antiretroviral-based Microbmentioning

confidence: 99%

The paradoxical effects of using antiretroviral-based microbicides to control HIV epidemics

Wilson

Coplan

Wainberg

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Couple-based studies permit exploration of developmental toxicants that may be mediated through exposure of the embryo or fetus to the components of seminal fluid via intracanicular exposure or by absorbance of seminal fluid components into the bloodstream of the mother (Benziger and Edelson 1983;Sandberg et al 1968). Semen collection provides the opportunity to measure biological and chemical components of the seminal fluid (Lay et al 2001;Younglai et al 2002), perform standard sperm analyses, and even examine spermatozoal gene expression profiles (Ostermeier et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Prospective pregnancy study designs for assessing reproductive and developmental toxicants.

Buck

Lynch

Stanford

et al. 2004

Environ Health Perspect

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The determinants of successful human reproduction and development may act as early as periconceptionally, underscoring the need to capture exposures during these critical windows when assessing potential toxicants. To identify such toxicants, couples must be studied longitudinally prior to conception without regard to a couple's ability to ascertain a clinically recognized pregnancy. We examined the utility and feasibility of prospective pregnancy study designs by conducting a systematic review of the literature to summarize relevant information regarding the planning, implementation, and success of previously published prospective pregnancy studies. Information concerning design elements and participation was abstracted from 15 eligible studies (from a total of 20 identified studies) using a standardized form. The primary author of each study was contacted to review our summary of their work and obtain missing information. Our findings confirm the ability to recruit women/couples from diverse populations using a variety of recruitment strategies. Among the studies we reviewed, 4-97% of eligible individuals were successfully contacted, with enrollment rates ranging from 42 to 100%. Length of follow-up varied from 3 to 12 months. A high percentage of women provided urine (57-98%) and blood (86-91%) specimens and most male partners (94-100%) provided semen samples. These data support the feasibility of this design.

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“…First, many kinds of exposures and chemicals affect human sperm quantity and quality. Second, the vagina absorbs a number of components of semen that can be detected in the female bloodstream within a few hours of sexual intercourse (Benziger and Edelson 1983;Sandberg et al 1968). This has possible implications for the exposure of embryos and fetuses to components of seminal fluid by both intracanicular and bloodborne routes and may even serve as a route of exposure for women.…”

Section: Mini-monograph | Home Collection Of Biospecimensmentioning

confidence: 99%

The value of home-based collection of biospecimens in reproductive epidemiology.

Rockett

Buck

Lynch

et al. 2004

Environ Health Perspect

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Detection, quantification, and prognosis of environmental exposures in humans has been vastly enhanced by the ability of epidemiologists to collect biospecimens for toxicologic or other laboratory evaluation. Ease of collection and level of invasiveness are commonly cited reasons why study participants fail to provide biospecimens for research purposes. The use of methodologies for the collection of biospecimens in the home offers promise for improving the validity of health effects linked to environmental exposures while maximizing the number and type of specimens capable of being collected in a timely and cost-effective manner. In this review we examine biospecimens (urine and blood) that have been successfully collected from the home environment. Related issues such as storage and transportation will also be examined as well as promising new approaches for collecting less frequently studied biospecimens (including hair follicles, breast milk, semen, and others). Such biospecimens are useful in the monitoring of reproductive development and function.

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Absorption from the Vagina

Cited by 80 publications

References 98 publications

The paradoxical effects of using antiretroviral-based microbicides to control HIV epidemics

The paradoxical effects of using antiretroviral-based microbicides to control HIV epidemics

Prospective pregnancy study designs for assessing reproductive and developmental toxicants.

The value of home-based collection of biospecimens in reproductive epidemiology.

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