The Global Campaign for Microbicides (GCM) – along with others
players in the field of microbicide research and development – is
dedicated not only to accelerating microbicide product development
but also to facilitating the widespread access and use of these
products, once they become available.
Currently, microbicide researchers and advocates are collaborating
with regulatory authorities in some countries to determine what
regulatory requirements a microbicide will have to meet to be
approved for public distribution. These regulatory bodies are
responsible for ensuring that medicines and products are safe,
effective, high quality, and manufactured and stored appropriately;
that health professionals and individuals have appropriate
information; and that promotion and advertising is fair and
balanced. The World Health Organization has convened a series of
regional workshops in Africa and Asia to help educate national
regulatory authorities about microbicide science, product
development and clinical trials. Countries with strong national
regulatory authorities like South Africa and India may be able to
develop regulatory guidance that will be helpful to other countries
with less capacity in the area of evaluating new products.
While all these efforts are ongoing, it is important for all of us
to make sure that public expectations are not raised to unrealistic
levels. The first Microbicides will only be moderately effective and
even these first products may still be several years away from being
approved for use anywhere. The first microbicide will not be
launched in every country simultaneously, or even nationwide in
those countries that are first adopters (most likely countries in
southern Africa).
When, where, how and to whom new drugs become available depends on a number of factors, including the adequacy of the health infrastructure in a country; the political will within the
government and the willingness of the population generally to demand access to the new drugs. NHVMAG is one of the many partner and ally organizations that GCM is working with – in many countries — on efforts to educate governmental officials and build the public awareness required to make an effective demand on decision-makers to start planning now for how microbicide roll-out will occur and how it will be funded when the first successful products become available.
Scaling up manufacturing capacity to produce a large volume of
microbicides is also critical to ensuring access. It can take 18
months to three years to scale up manufacturing capacity
sufficiently to produce enough of a product for commercial
distribution. So it is important that this process begins early,
possibly even before the clinical trial of the candidate microbicide
is complete because if scale-up doesn’t happen, there is a risk of
delaying availability of an effective product. Product developers
and others in the field have begun to develop specific plans to
accelerate access by identifying manufacturers and planning for
manufacturing scale-up now.
Cost, of course, is also a key factor. At least one candidate
microbicide has already been stopped from going into human testing
because it was both too difficult and too expensive to produce. The
researchers decided that it didn’t matter whether the product worked
or not because it would be too expensive to be made widely available in poorer parts of the world. So they abandoned work on it.
Even products that are cheap to produce may still not be affordable
to many people who need them. For this reason, work is underway to
develop mechanisms to enable donors and/or governments to subsidize both product purchase and the programs required to deliver them.
Microbicides will be delivered through some mix of public, private,
and social marketing systems. This means that significant
investment also has to be made in strengthening commodity systems for delivering other public health goods, and that the microbicides field will be building on these efforts.
We all know that, historically, most new drugs are introduced first
in developed countries where people and health systems can afford to pay for them. It can often take a decade or more for products
to “trickle down” to developing country markets, and many new drugs and other health innovations never reach people in developing
countries. But advocates and researcher are determined that access to microbicides will follow a different pattern and we have a good
reasons to believe that this is possible. The reason is that
microbicides, unlike most drugs and prevention products, are not
being developed by pharmaceutical companies. The pharmaceutical
companies are driven primarily by the need to make profits. But
most of the organizations working to develop microbicides are not-
for-profit or academic institutions, and are supported by
philanthropic or government funding. So they can afford to be
concerned more with the public health goal of preventing HIV
infection, rather than profit.
The microbicide field, therefore, is primarily focused on ensuring
access to microbicides at an affordable price. Several donor and
product developer require in their contracts that a product can be
made available at low cost in resource poor settings. Microbicide
advocates have already started working with regulators,
manufacturers, governments, health care providers, donors and other civil society actors to do what needs to be done to make sure that people who want to use microbicides – especially those at highest risk of HIV infection — are able to get them consistently, at a convenient place, at an affordable price, and use them in their
daily lives.
Anna Forbes
Deputy Director
Global Campaign for Microbicides
1800 K Street NW, Suite 800
Washington DC , 20006
USA
Researchers and Community advocates under the aegis of the New HIV Vaccines and Microbicide Advocacy Society (alias NHVMAG) have expressed disappointment over recently released results that showed that Carraguard, a microbicide candidate undergoing Phase 3 trials failed to effectively protect women against the risk of HIV infection.Population Council, an international non-profit research institution had tested Carraguard, (a microbicide candidate developed as an odorless, clear gel made from carrageenan, a derivative of seaweed for its) effectiveness in a study conducted between 2004-2007. The study enrolled 6,202 women participants in South Africa. Trial results showed that the product was safe and acceptable to women, but did not reduce their risk of acquiring HIV.Coordinator of NHVMAS, Dr Morenike Ukpong noted that result of the Carraguard study comes as a disappointment to the Nigerian advocates who have continued to wait for good news from the field
We applaud the efforts of the researchers at completing the first large-scale effectiveness microbicide trial. We also appreciate the efforts the researchers are making in ensuring transparent communication with trial participants and with African stakeholders about the trial. We also are aware of the hard work of the trial site staff at ensuring effective community participation in the Carraguard study and this we find exemplary.
NHVMAS and the community of Nigerian advocates continue to applaud the current partnership observed between researchers and the community: Dr Bode-Law Faleyimu of NHVMAG noted that “this is truly an effort at true stakeholders involvement and teamwork. If this mutual respect, sharing and involvement continues, we believe we will see less futile research and more successful trials in the future
Ukpong however noted that the disappointment on the part of the advocates only reinforces the need to invest expediently in future microbicide researches.. Quoting Lori Heise of the Global Campaign for Microbicides a leading US based Microbicides Advocacy Organization, New drug development is always a long term struggle and typically hundreds of product leads fail for every one that succeeds, but discouragement is a luxury we can’t afford. Ukpong noted that “Our responsibility now is to learn as much as possible from this trial to inform and guide future research, improve future trials, better predict efficacy and understand how best to partner with communities and improve the standard of care offered to participants.
Nigeria had hosted two phase III microbicide trials in the immediate past (SAVVY and CS3). The disappointing results from the two studies has however not dampened the , enthusiasm of researchers and advocates who are hopeful that other ongoing global research efforts will yield positive results for a safe, effective and affordable microbicide in the not too distant future .
Though the HIV prevalence in Nigeria is decreasing based on the 2001, 2003 and antenatal clinic Sentinel Survey results from the Federal Ministry of Health, the statistics still indicate that women are worse affected by the epidemic.
Vaginal microbicides which are being developed as a female-initiated method for reducing male-to-female transmission of HIV and possibly other sexually transmitted infections (STI) when used during sex, would therefore be a welcome intervention that will boost the quality of currently existing HIV prevention tools in Nigeria
The New HIV Vaccine and Microbicide Advocacy Society (alias NHVMAG) is a coalition of stakeholders (advocates, researchers, policy makers, media persons, academia and ethicists) engaged directly and indirectly with New HIV Prevention Technology Research and Development in Nigeria
www.nhv-mag.org
Contact: Morenike Ukpong,
+ 234 803 2459 256;
toyinukpong@yahoo..co.uk
The state of clinical trials in developing countries came under
scrutiny recently.And the crux of the matter was the right of
volunteers to leave any critical trial without any undue harrassment
or loss of priviledges.
Africa like most developing parts of the world has been the centre
of most clinical trials expecially by western drug
companies.Clinical trials are organised testing of a drug
compound,vaccines or medical device in humans to ensure that the
drug is efficacious and safe.
Volunteerism in clinical trials depicts freedom to leave without any
strings attached.Do clinical trials conducted in developing
countries actually allow such freedoms?
At a media roundtable organized by Journalists Against AIDS (JAAIDS) Nigeria in collaboration with the Nigeria HIV Vaccine & Microbicides Advocacy Group (NHVMAG),Dr. Morenike Ukpong, NHVMAG Coordinator,Ms. Marrie De Cernival of SIDACTION,France and Mr. Azubuike Nwagbogu of the Clinical Trial Unit the National Agency for Foods and Drugs Administration and Control (NAFDAC) bared their minds on various forms of unethical practices with regards to clinical trials.Some of these, according to the speakers, include the poor performance of regulatory bodies tasked with such responsibilities like NAFDAC and the seeming negligence of institutional review boards who are supposed to also monitor trials and other researches being conducted in tertiary institutions across the country. In her presentation, Dr. Ukpong said the freedom to participate in a trial or to opt out of should be part of the fundamental rights of trial participant. She added that participants must also be given full briefing on the trial processes and procedures and comprehension must be assessed before seeking for signing of consent forms.But she lamented that this is oftentimes not so. She tasked the media to be alert and help correct these anomalies. “Just like the media coverage of the court proceedings on the controversies surrounding the Pfizer trials, the media must play its role as an effective watchdog so that government agencies and companies can do what is right.” Ms. De Cernival identified poverty in developing countries as a factor that forces participants to remain in trials because they can’t afford to pay for such treatments themselves. `In developing countries like Nigeria, participants involved in a clinical trial don’t often have the same reasons for participating as that of researchers as many participate primarily because of the free benefits that will accrue to them.” This is not the case in developed countries where most trial participants are not interested in free medical care since they can easily access that as provided by the government health plans for citizens.
“In the western world, participants often volunteer for trials
because they are interested in the questions the research aims to
answer. Some also do it because of the benefits the results could
bring to humanity.”
Mr. Nwagbogu of NAFDAC, said the agency is working to ensure that
all trials going on in the country are registered with it and are
appropriately approved. He said when applications for approval to
conduct clinical trials are submitted to NAFDAC, its clinical trial
unit first studies the research protocols being presented by the
proponents before making a final judgment on whether to approve or not. He agreed with the other speakers on the significance of informed consent of participants in any research effort, and their freedom to opt out anytime they choose without any backlash from the researchers.
`Overall, before approving any research whatsoever, we make sure the subject of research is something that is important to the nation, is for the greater good of the society and that the interests and
welfare of all trial participants are protected”.
The NAFDAC officer admitted that some researches still go on in the
country without NAFDAC’s approval.However, such efforts are illegal
while the research findings, no matter how laudable, also wear the
cloak of illegality. He warned that the unscrupulous masterminds
behind such illegalities are also liable to criminal prosecution.
O’Femi Kolawole
Email:ofemi@nigeria-aids.org
Prevalence of HIV and other sexually transmissible infections in relation to lemon or lime juice douching among female sex workers in Jos, Nigeria
Godwin Imade A , G , Atiene Sagay A , Daniel Egah B , Viola Onwuliri C , Matthew Grigg E , Christopher Egbodo A , Tom Thacher D , Malcolm Potts F and Roger Short E
Corresponding author. Email: ereimade@yahoo. co.uk
Abstract
Background: The rates of sexually transmissible infections (STI), including HIV, are high among female sex workers (FSW) in Nigeria and the use of various local vaginal cleansing agents to prevent infection is a common practice. The present study was aimed at determining whether any association exists between current lime or lemon douching and the prevalence of STI and HIV infections among FSW in Jos, Nigeria.
Methods: Consenting FSW who were users of lemon or lime (UL) or non-users (NUL) were recruited for the study between May and September 2006. A structured questionnaire was administered by trained counsellors. Pre-HIV test counselling was done. Participant’ s blood samples were tested for HIV and syphilis. Genital examination was done and high vaginal and endocervical samples were collected. The samples obtained were processed for STI using standard laboratory procedures. FSW found with treatable STI received free drugs. HIV results were disclosed after post-test counselling and positive FSW were referred to a HIV/AIDS facility for care, support and antiretroviral therapy.
Results:
A total of 398 FSW (86 UL and 312 NUL) participated in the study. Their mean age was 27.6 ± 7.0 years (range 16 -63 years). HIV prevalence was high for both UL and NUL: 48.8 and 48.2%, respectively (odds ratio 1.0; 95% confidence interval 0.6 -1.2, P = 0.9427). The rates of bacterial vaginosis were not significantly higher in UL (UL 55.8%, NUL 44.0%, odds ratio 1.59, 95% confidence interval 0.96–2.65, P = 0.06). There were no associations between the use of citrus douching and other STI.
Conclusion: There were no significant associations between the prevalence of STI and HIV and lime or lemon juice usage.
Sexual Health 5(1) 55-60. Published: 22 February 2008
Full text DOI: 10.1071/SH07047. © CSIRO 2008
There are different types of microbicides being tested. An analogy is
the detergent. Detergents are meant for laundry, yet there are
differnt types: omo, surf, klin, elephant etc. So is it with
microbicides. There are different microbicides with different names
and different modes of actions.
Below, we would quickly go through what the types of microbicides are
and how they work
Moderator
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
Curently there are five groups of Microbicides
1. Detergents also known Surfactants
2. PH modifier also known as body enhancer
3. Polyanions also known as fusion/entry inhibitors
4. ARV based microbicides
5. Unknown mechanisms
1. Examples of detergents
a. Nonoxynol-9 (N9): a detergent present in spermicides and some
vaginal lubricants. Regular and frequent use of the product destroys
the vaginal epithelium
b. SAVVY: Though a surfactant, was found safe but not effective
in preventing HIV infection due to the low HIV incidence in the
regions of study for efficacy to be established
2. Polyanions
a.CS3 also called Ushercell. Found associated with an increased
rate of infection at some of the clinical sites through unknown
mechanisms.
b. Pro 2000 which is a ulphonated polymer. Its inhibits the
attachment of the virus to cells. They are charged polymers. Studies
being conducted by MDP and HPTN use these products. Concentrations of
0.5% is currently being studied in 2 trials
c. Carraguard: Contains Carrageanan which is a product from
seaweed. It binds to the body cells or disease causing organisim
before they can invade and attach. Studies show the product is safe
but not effective in preventing HIV infection. If also does not
prevent pregnancy
3. PH modifier or body defence enhancer
a. Buffer gel: This is a broad spectrum microbicide. Buffer gel
works by keeping the vagina at a low pH (the normal PH) during and
after sex. HIV prefers a basic environment that is, an environment
with a high pH. Studies have shown that HIV is inactivated at a PH
below 4 to 5.8. Buffer gel thus works by boosting the natural body
defence mechanism: increases lactobacilli or rapidly acidifies the
ejaculate
4. ARV Based Microbicide
This group of microbicide are currently being studied. They ARV based
microbicide would not be able to prevent the vagina cells from being
infected BUT should prevent HIV from replicating within the infected
cells. There are a lot of current studies going on at preclinical and
clinical phases. As you follow Microbicide research, you would read
and hear about PMPA (tenofovir based microbicide), UC-781, TMC 120
and MIV 150.
5. Unknown action
Currently, India is studying a herbal preparation for use as
microbicide called Praneem. Its possible mechanism of action is not
known.
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
