Glossary of terms used in microbicides research

Arms: the group in a clinical trial, usually known as the control
group and intervention group. Comparing results from the different
groups enables researchers to determine whether and how well a new
intervention (treatment, vaccine, prevention method, or what ever
is being tested) works. Some studies are designed to test more than
one treatment; these would have more than two arms/group.

Cellulose sulfate (CS) – a gel that was tested as a possible topical
microbicide but in 2007 was found not to be effective. Researchers
thought that CS could potentially block HIV infection (and possibly
other STI infections) by creating a barrier between the virus and
the woman’s cells in the vagina, which the virus targets for
infection. This would make it more difficult for the virus to enter
the woman’s cells.

Cohort- a defined group of people who are followed over a period of
time during a trial to see if anything changes in their situation
(e.g. a group of HIV negative women could be treated as a cohort).

Coital act – sex involving the penetration of a penis into a vagina.

Control group- the comparison group in a clinical trial. This is the
group of trial participants who do NOT receive the intervention that
is being tested. Depending on the intervention being tested, they
usually either receive no treatment at all, a placebo, or current
treatment in use.

Diaphragm- a small latex silicone dome/cup that covers the cervix
(the lower part of the uterus, or womb, that connects to the
vagina). A diaphragm prevents pregnancy by covering the cervix and
blocking sperm from entering the uterus. It also blocks viruses and
bacteria from entering. Trails have shown that the diaphragms DO NOT prevent women from HIV infection.

Double blind- in a double-blind trial, neither the participants nor
the researchers know which participants are in the control group and
which are the intervention group. This is done to reduce bias
from both researchers and participants. An independent group of
experts who are not researchers in the trial, the Data Safety
Monitoring Board, look at the different points in the trial.

DSMB (Data Safety Monitoring Board)- an independent panel of experts who are not researchers associated with the clinical trial, but who have responsibility to look at the results at different points
during a trial to make sure that it is not ethically necessary
to stop the trial either because the intervention causes greater
risk or is overwhelmingly successful.

Efficacy versus Effectiveness- Efficacy refers to how well an
intervention works under controlled situations (such as in a trial).
Effectiveness refers to how well an intervention works in real life
settings.

Epithelium- layer of cells lining the vagina, the cervix, uterus(and
other body cavities).

Fusion inhibitor- a microbicide that would work by preventing HIV
from attaching to a woman’s cells.

Interim data analysis- conducted by the DSMB. Data from the control
and intervention groups of a trial are examined and analysed during
the trial at different points, not just at the end when all the
data is completely collected and the trial is finished. These
interim data analyses are used to make sure that the trial does not
need to be stopped early for safety reasons, or because the
intervention being tested is either causing harm or is shown to be
effective.

Intervention groups- the group of participants receiving the
intervention (e.g. new treatment, vaccine, prevention method) in a
clinical trial.

Microbicide- any compound or substance that can be used to reduce
the ability of a virus or bacteria to infect cells. The microbicide
candidates being developed and tested now for HIV prevention are all topical gels or creams that are inserted into the vagina (or anus),
and that coat the cells lining the reproductive tract.

Second and third generation microbicides- first generation
candidates were the first possible microbicides that were tested but
proven not effective. Second and third generation candidates are
those more recently developed that use and build on the results
obtained from the candidates that didn’t work, as well as the new
information and knowledge about HIV. Some of these more recent
microbicide candidates are ARV- based.

Mode of action- how a treatment works. There are several possible
modes of action for microbicides. Some acts as physical barriers,
blocking the virus from entering a woman’s cells, others prevent HIV
from entering and infecting the woman’s cells, while others
preventing the virus from making copies of it self.

N-9( (nonoxynol-9)- a spermicide (kills sperms to prevent pregnancy) that was tested as a microbicide to prevent HIV infection. It was NOT affective, and its regular use increase women’s risk of HIV infection. N-9 works as a surfactant, by breaking up the membrane (outer layer) of the virus, but its regular use also causes
irritation and lesions in the vagina, which made it easier for HIV
to enter the woman’s cells.

Oral prophylaxis- taking anti-retroviral pills, either before
sexual exposure (pre-exposure prophylaxis) or after sexual exposure (post-exposure prophylaxis) to HIV.

Pap test (also known as a pap smear)- a medical screening test,
where calls are taken from the cervix and looked at under a
microscope to see if there are any cells that look abnormal. The pap
smear is a way to screen women for early signs of cervical cancer.

Phase 3 clinical trials- randomized clinical/controlled trials on
large groups of participants to look at the efficacy of a new
intervention. Phase 3 trials are begun only after phase 1 and phase
2 trials (which are smaller studies that look at safety, at doses,
and at efficacy) are successfully completed.

Placebo- in a blind or double-blind clinical trial, the control
group receives a placebo. This is not the treatment being tested,
but it looks exactly like the treatment. For typical microbicide
trials, the control group received a gel that looked and was used
the same as the gel given to the intervention group, except that it
did not contain the microbicide. Placebos are used in blinded
clinical trials so that participants and researchers do not know
which participants are in the control group and which are in the
intervention group.

Post- exposure prophylaxis (PEP)- taking oral anti-retroviral
medication for a short period of time after exposure (such as an
accidental needlestick for a health care worker), or possible
exposure to HIV (as in the case of rape). PEP should begin 2-24 hours after the exposure to HIV, and no later than 72 hours. There is evidence that PEP can lower tha risk of HIV infection after exposure.

Pre-exposure prophylaxis (PEP)- taking oral anti-retroviral
medication before HIV exposures. Currently, clinical trials are
being done to determine the efficacy and effectiveness of PEP for HIV prevention.

Randomized clinical/controlled trial- a study to determine whether
and how well a medical intervention (e.g. a drug treatment, a
vaccine, a prevention method, etc.) works. Usually, there are two
groups (also called arms), the control group and the intervention
group. The control group either gets no treatment, the current
standard treatment, or a placebo. The intervention group gets the new intervention. Results from both groups are compared to see whether and how well the intervention works. Participants are placed into the groups randomly (by chance, without knowing which groups they are placed in). There are stages of trials. The first stages test
with small numbers of participants to make sure the intervention is
safe. Later stages enroll more people ad test the intervention’s
efficacy.

Sero-conversion- becoming infected with HIV. In clinical trials,
this term is used to refer to people who were HIV negative when they
enrolled in the trial, who became infected during the trial.

STI- sexually transmitted infections.

Surfactant microbicide- a microbicide that works by disrupting or
breaking up the membrane (outer surface) of the HIV virus.

Target cells- type of cell that HIV, or another virus or bacteria,
infects.

Tenofavir – an antiretroviral (ARV) that is currently being tested
in gel format as a possible topical microbicide to prevent HIV
infection.

HIV vaccine- a vaccine that would prevent HIV infection. There is
no effective HIV vaccine at present, but there are several possible
vaccines being developed and tested.

Vaginal lesions- small scrapes of tear in the vaginal, which may be
cellular entry points from HIV.

Kingsley Obom-Egbulem, Delhi.
Nigeria-AIDS.org
February 28,2008

M2008:Do you understand the language of Microbicides research

Cohort. Candidate. Fusion inhibitors. Placebo. Double blind. HPTN
035. Randomization. Surfactant. “Wait a minute! Sounds like some
words coming out of a science fiction movie.

But this is not about science fiction or even a movie. It was the
2008 Microbicides Conference held in New Delhi, India and these were definitely the major language spoken at the conference .You are sure to hear them at any of the sessions for which you had to sit in. Navigating through the microbicides conference was indeed an
interesting process. It’s even a challenging process especially for
someone like us who must capture most of the crucial moments and
report all the track A, B and C sessions to a mixed audience of
journalists, PLWH, scientists and even other lay men. Was it
difficult?

Well, to some extent, yes. But when you try to catch up and seems
this researcher or principal investigator (PI) is beginning to speak
in tongues again, you simply switch off, fiddle with your blackberry
and send an sms or email, or take your leave. Some delegates are
even inconsiderate -they just sleep and snore on loudly and care
less what is being presented.

And as soon the speaker is done…they join every one in the usual
round of applaud that greets each presentation no matter
how “senseless” or “boring” it must have been.

While it is right to state that there are some people who had no
business being at the microbicides conference, some of the speakers especially scientist needed to be schooled in the art of
communication. Specifically, the task here is how
to “communicate”(not present) study findings to a mixed audience.

Well Drs. Sharon Hiller and John Mellors actually stood out among
the crowd here. They communicated during their presentations. They
simply spoke in “is and was; A, B and C”. Dr. Hillier’s presentation
on the Tenofovir study by the Microbicides Trial Network (MTN) and
Dr. Mellor’s role play illustrating the science of ARV treatment and
drug resistance was a classic.

I don’t know if it’s a Pittsburgh tradition (since they are both
from Pittsburgh) but they gave more sense to Judge Edwin Cameron’s postulations at M2006 in Cape Town that “Science is useless if it has no social relevance”. One can take that further to say that research is useless if it can’t be simply communicated to those who would benefit from it.

The microbicides conference is fast becoming a prestigious
conference that enjoys global following and efforts should be made
to attract advocates and supporters who can really discuss the
issues with a lay audience. Understanding the language is therefore
a major step in this direction Just in case one is forced to think that the microbicides conference is not an avenue for laymen to acquire research education, even some doctors I spoke with who were attending the conference for the first time heard Greek and Russian during some of the sessions. Well…for those who believe in self-development and really want to make progress as advocates or communicators who must educate people as we hope for a breakthrough in microbicices research development efforts, here is a glossary of terms used in microbicides research graciously developed by Gender AIDS Forum, South Africa.
www.gaf.org.za

The diaphragm: A Female-initiated barrier methods

Despite the overwhelming need for improved options for devices that can protect a woman from both pregnancy and STIs and the proven
effectiveness of a condom to address this, the female condom is still
poor availability 14 years after product approval. This is chiefly due
to price: in 2006 it was estimated to cost 27 times more than the male condom. This has limited its access even where there is a demand

To achieve a very significant price reduction, use needs to raise the
current uptake from 14 million in 2005 to at least 300 million
worldwide . Current efforts at facilitating a price reduction and
increasing possible uptake includes the development and producting of latex female condoms. India is a known production site for latex female condoms

A number of country programmes are expanding access to female condoms.
A good example is India with the Government proactively engaged with piloting programmes that would increase use and female condom uptake. UNFPA is also developing large-scale projects with a number of partners. Further uptake could be facilitate through NPT clincial trial sights especially those conducting studies on female initiated barriers and microbicide studies. Phase III Microbicide trials engage over 4,000 women in their studies and indirectly have contact with over twice that number. Including female condoms in the prevention package and empowering women to use this condom (appropriate site demonstration of female condom insertion) would help further in its uptake. There has also been interest in the adaptation of the diaphragm (a family planning device which covers the upper part of the vagina known as the cervix) and other cervical barriers for HIV prevention. The cervix is known to have a lot of CD4 cells and thus an active point for HIV ifnection. Protecting the cervix from HIV infection may therefore possibly reduce women’s rate of HIV infection However the first major study of the diaphragm failed to show benefit. This was known as the MIRA study which engaged about 5,000 women to use a diaphragm and lubricant, or lubricant alone. The study found no significant difference in HIV incidence between the study arms (those that used the diaphragm and lubricant and those that used lubricant alone). A study of the effectiveness of the diaphragm in preventing sexually transmitted infections (STIs) is however still underway in Madagascar. we do know that STIs increase vulnerability to HIV infection because it causes ulcerations in the skin, vaginal lining or lining of the wrine tract in male thereby creating a route through which the virus could get into the body.

However, not all diaphragms are of the same design, and different
devices may have differing acceptability. A range of products are now
being developed, some designed to be used with a microbicide:

•BufferGel Duet: the Duet is a sombrero-shaped diaphragm which, when lubricated with microbicide, should ensure coverage of the
microbicide in the cervix and the vagina .

•SILCS diaphragm (PATH) is a single-size cervical barrier, designed
to provide the same effectiveness as standard diaphragm, while being easier to supply and provide. Extensive input from women in developed and developing countries ensures the design is comfortable, easy to use, and sleek.

HSV-2 suppression: efforts at preventing HIV infection

HSV-2 infection (HSV-2 infection causes a form of herpes infection)
appears to double or triple the risk of HIV infection by creating
lesions through which the virus can easily enter the body. It also
increases the ability of a person who is infected with the HIV and
HSV-2 to infect others.

About 80-90% of HIV-positive individuals and 50% of HIV-negative
women are HSV-2 infected. Because of the link between HSV 2 infection and HIV infection there has been considerable interest in testing whether HSV-2 suppressive treatment (treatment that would reduce the ability of HSV-2 to multiply in the body) in HIV-negative individuals can reduce their risk of HIV acquisition. Studies are also looking at the possibility of the use of HSV-2 suppressive therapy reducing the ability of HIV positive individuals to infect their sexual partners. Results to date have been disappointing. Two large studies failed to find any protective effect of daily HSV suppression therapy in HIV- negative women or men who have sex with men. A third study HIV- discordant partnerships (one partner is HIV negative and another is HIV positive) where the HIV-positive partner is coinfected with HSV- 2, is ongoing in sub-Saharan Africa and expected to report in February 2009.

Post exposure Prophylaxis (PeP)

Post-exposure prophylaxis (PEP) is a course of anti-HIV medication
that may prevent HIV infection after exposure. It can take HIV
between one and five days to become established in the CD4 T-cells
and lymph nodes after exposure. It is thought that a course of PEP
can act during this time to prevent the virus from taking hold, thus
preventing seroconversion in the person who was exposed.

Currently, the focal emphasis in the use of PEP is amongst health
workers who may be exposed to HIV infection due to needle pricks or other exposures to infected blood and blood products during patient management. There are however, renewed interest in preventing possible HIV infection through rape by the use of PeP. In South Africa, for example, where the incidence of rape is the highest in the world, it has been estimated that more than one million women are raped each year. Rape therefore constitutes a possible HIV infection risk route (when raped by someone who is HIV infected, not only is the semen loaded with HIV virus but the tears from forced penetration also further helps the entry of the virus into the body).

Evidence from studies show that very few cases of HIV transmission
have occurred after PEP, with only six reported transmissions
worldwide in healthcare workers since 1997. Studies of PEP after
sexual exposure have also been promising. For example, a Brazilian
study of gay men found that fewer men became infected after sexual exposure if they took a course of PEP than did a similar group who chose not to take it . A second Brazilian study found no
seroconversions in victims of sexual assault who took PEP within 72
hours of exposure. Similarly, only one of 500 sexual assault victims
in South Africa who were treated within 72 hours of the assault
subsequently developed HIV infection .

Despite this evidence, there are drawbacks to PeP. This include low
uptake due to a number of factors including lack of awareness, and
poor adherence, chiefly due to drug side-effects.