AIDS August 2001;15:1595-1602
Brief Review: the authors think that the cervix is the key entry point for HIV.
And that by combining the use of a cap by the women which protects the cervix
with a microbicide HIV can be prevented. This sort of a contraceptive approach
would give the woman control in sexual situations as opposed to negotiating
condom use. However, the authors are merely proposing such a concept. They
support their thinking with preliminary research on STD transmission, animal
research, and theories which may be well based. But, in the end the authors
themselves conclude that we need research studies to explore and confirm whether
these approaches are effective. The authors conclude: "To our knowledge, no
studies of the HIV preventive capabilities of internal barrier devices have been
published, are ongoing, or are planned and funded. Clinical, epidemiological and
biological evidence strongly support the hypothesis that combining a microbicide
with such a barrier will enhance protection. Direct tests of this hypothesis
with controlled trials are well justified and should be a high priority".
authors- Thomas R. Moench; Tsungai Chipatoa; Nancy S. Padianb >From ReProtect,
LLC, Baltimore, Maryland, USA, the aDepartment of Obstetrics and Gynaecology
University of Zimbabwe, Harare, Zimbabwe and bAIDS Research Unit, Department of
Obstetric Gynecology & Reproductive Sciences, University of California San
Francisco, California, USA.
Introduction
The need for woman-controlled barrier contraceptives that protect against both
bacterial and viral sexually transmitted pathogens is widely recognized. In the
absence of an effective vaccine or treatment, contraceptive methods capable of
preventing sexual transmission of HIV as well as other sexually transmitted
diseases (STD) are vital for protecting the health of women. Moreover,
widespread violence against women, double standards of sexual behavior, and the
imbalance of power in many sexual partnerships make methods initiated and
controlled by women critically important. These issues may severely limit
existing options for protection among women who cannot negotiate sex with their
male partners without being accused of cheating, of being ‘loose’ women, or of
accusing their partners of infidelity.
Vaginal microbicides (topical chemical barriers that protect against acquisition
of a variety of STD pathogens, including HIV) may provide such alternative
woman-controlled methods. Compared to male and female condoms, microbicides are
expected to interfere less with intimacy and sexual pleasure, and be more
discrete. Because detergents like nonoxynol-9 (N9) are microbicidal as well as
spermicidal, several existing N9 contraceptives have been tested in
observational and controlled trials as microbicides for HIV/STD prevention.
Modest protection against Chlamydia and gonorrhea has been shown, but HIV
prevention studies have yielded mixed results and overall, the protective effect
for HIV appears doubtful. In fact, the most recently completed trial reported
greater HIV transmission in the women using N9 compared to those using a placebo
gel, possibly due to detergent-induced compromise of the epithelial barrier
after intensive use. New microbicides (only some of which are spermicidal) are
being developed for vaginal protection, in an effort to improve efficacy,
safety, and acceptability compared to existing detergent-based products such as
N9.
Although many of these new microbicides show robust activity against HIV and
other STD pathogens, and some also appear to be less toxic than N9, achieving
reliable protection with microbicides remains a significant challenge. We
contend that the likelihood of success of such products could be greatly
increased by an alternative prevention approach, namely the combination of a
microbicide and an internal barrier device that protects the cervix. Like
condoms, these devices (diaphragms, caps, and other novel designs) create a
physical barrier that covers the cervix. Yet because they are worn completely
inside the vagina, they avoid the obtrusiveness that limits the acceptability of
male and female condoms. With microbicide applied on both the cervical and
vaginal sides of these devices (as is commonly recommended for contraception in
the UK, but not in the USA or other countries), they should offer all the
benefits of the microbicide, with additional benefits provided by physical
protection of the cervix.
Although internal barrier devices cover the cervix, they do not provide a
barrier for most of the vaginal epithelium. Thus, if transmission susceptibility
were distributed equally across all epithelial surfaces, internal barrier
devices might add only modestly to the protection given by the microbicides with
which they were used. However, substantial epidemiological and biological
evidence suggests that susceptibility is not evenly distributed, but that the
cervix is a site of particularly high susceptibility to HIV and STD
transmission. Thus, internal barrier devices that cover the cervix may enhance
significantly the protection against HIV and STD that may be provided by
microbicides alone. In addition, applying the microbicide to the vaginal side of
the barrier may confer vaginal protection as well.
Currently the traditional diaphragm and cervical cap are the only tested and
approved internal devices that provide physical protection of the cervix.
However, several new barrier methods are under development or at various stages
of testing. These method include the Leah's shield (similar to a loose fitting
cervical cap made of rubber with a loop for easy removal), the Femcap (also
similar to the cervical cap but with a brim designed to fit into the vaginal
fornices), the SILCS diaphragm [a new single-size design (SILCS Inc., Tinton
Falls, New Jersey, USA) expected to be easier to insert and remove], and
disposable diaphragms (some of which may be provided with microbicide preapplied).
Evidence for the importance of the cervix in acquisition of STD and HIV
Cervical infection with bacterial STD
Although to date, there have been no experimental studies (i.e., controlled
trials) to evaluate the effect of diaphragm use and STD acquisition, there have
been several observational studies (case–control or cross-sectional designs)
that report a protective effect of diaphragms in decreasing susceptibility to
STD and associated long-term sequelae. All of the studies compared diaphragm
users to non-users, and all used some type of multivariate analysis to control
for known co-factors or confounders such as socioeconomic status or age.
Although not always specified, in most studies women who used diaphragms used
them together with spermicides. Thus, although we cannot separate the protective
effect of diaphragms from that conferred by spermicides used alone, this
limitation does not affect our fundamental argument that diaphragms used
together with microbicides may offer significant protection. Table 1 summarizes
these results. Because the majority of these studies were not designed to test
the efficacy of the diaphragm as their primary objective, and (as stated above),
because they are all observational studies and thus subject to biases inherent
in that design, results in the table must be seen as suggestive rather than
definitive.
The susceptibility of the cervix to HIV
To date, no studies have examined the protective effect of physical coverage of
the cervix and HIV acquisition. However, because of its fragility, frequent
compromise by classical STD, and the presence of HIV receptor sites (all of
which are discussed below), the cervix is probably more susceptible to HIV than
is the vaginal tissue. The importance of the cervix in acquisition of HIV
infection is suggested by a recent experiment in which rhesus macaques were
infected vaginally with SIV [25]. Using in situ hybridization to detect SIV-infected
cells, the first cellular targets were found to be located in the lamina propria
of the columnar endocervical epithelium. These cervical cells were detectably
infected by day 3, whereas the vaginal mucosa was not infected until day 12, a
time when virus was systemically disseminated. Thus, the cervix appeared to be
the site of initial infectious entry. The cervix may also serve as a portal
allowing pathogen access to the upper genital tract. Human cervical tissue
section explants are easily infectable with HIV, as are uterine and fallopian
tube sections [26]. This suggests that upper tract access may be followed by
infectious entry of HIV.
As is apparent from these results and those reported for STD above, overall,
there is a consistent indication that the cervix is an important infection site
for STD and HIV. Below we review biological mechanisms that may account for
these observations.
The articles goes on to explore the authors research in animals and with STDs in
supporting why the cervix appears to be a place where if protected from HIV
infection can be prevented. They contend the cervix is a likely site of entry
for STDs and HIV. Their is some conflicting research both supporting and not
supporting that the cervix is a key site for transmission of HIV and the
articles discusses both sides of the research but obviously the study authors
think the cervix is the key site.