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.

New HIV Prevention technology pipelines – ARV treatment of index partners

There is strong evidence to suggest that antiretroviral treatment
reduces HIV transmission by lowering viral load. Evidence from at
least one study show that current efforts to expand access to
treatment in sub-Saharan have probably resulted in a major reduction in HIV transmission. A three year study in Uganda of antiretroviral treatment coupled with intensive adherence support, behavioural counselling and partner testing led to an estimated 90% reduction in onward HIV transmission, CDC researchers calculated.

An ongoing study, is trying to determine if earlier treatment in
individuals with CD4 counts between 300 and 500 is more likely to
reduce HIV transmission in serodiscordant couples than treatment
initiated according to standard guidelines (the standard guideline
recommendation is that ARV treatment should start when the CD4 count is 200 or less). The study is recruiting in Brazil, India, Thailand, Malawi and Zimbabwe, and expected to report by 2013.

The world awaits the result of this study!

New HIV prevention technology pipelines – the story of PreP

Pre-exposure prophylaxis (PrEP) is the use of antiretrovirals prior
to exposure to HIV to prevent infection. PrEP is intended for use by
people who may be at frequent risk for HIV. This includes people who engage in high-risk behaviour groups such as sex workers, injecting drug users, and people who have unsafe sex with a multiple partners (or whose partners have multiple partners). Currently, no
antiretroviral is yet approved or in use as PrEP. Serodiscordant
couples (sexual stable relationships where a partner is infected
with HIV and the other is not) could also benefit from PreP use.

Much of the data on PrEP result from research conducted in monkeys.
In general though not clearly so, these studies have demonstrated
that PrEP can decrease the risk of infection to varying degree.
these studies have also used different models for testing, making
comparisons of results across studies difficult.

The only human data to date, from a Family Health International
study of tenofovir PrEP in which recruitment was abandoned at two
sites due to a controversy over post-trial care, show no serious
safety concerns during an average of nine months’ follow-up.

Four PrEP studies are ongoing and three others are planned for
rollout as of february 2008. The ongoing studies are:
• An efficacy study tenofovir among injection drug users in
Thailand, sponsored by the United States Centers for Disease Control and Prevention (CDC) – expected to report efficacy results in 2009.

• A safety study of tenofovir among men who have sex with men in the United States, also sponsored by the CDC – expected to report safety results 2009.

•An efficacy study of Truvada among heterosexuals in Botswana, also sponsored by the CDC – expected to report efficacy data in 2010.

• An efficacy study of Truvada among men who sex with men in Peru
and Ecuador sponsored by the NIH – expected results in 2010.
The risk of HIV transmission is influenced by a number of biological
and environmental factors, including stage of disease, number of
exposures, viral load in blood and semen, as well as the presence of
other sexually transmitted infections. In addition, studies have
shown that most transmission occurs during the acute stage of
infection or at the late stage of disease, when viral loads are
high. According to studies from serodiscordant couples conducted in
Africa, HIV-positive individuals in the acute stage of infection
were responsible for 43% of all HIV transmissions. Knowing this. HIV
control strategy must be multiprong with a wide range of use options
for all persons affected by epidemic.